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Minerals:

Major and Trace

Major Minerals

sodium
chloride
potassium
calcium
phosphorus
magnesium
sulfur

Minerals in a 60-kilogram (132-pound) Human Body

MAJOR MINERALS
The major minerals are those present in amounts
larger than 5 g (a teaspoon). A pound is about
454 g; thus only calcium and phosphorus appear
in amounts larger than a pound.

TRACE MINERALS
There are more than a dozen trace minerals,
although only six are shown here.

Amount (g)

Sodium
fluid volume regulator, electrolyte

balancer
source
mostly in processed foods
deficiency
must be replaced with water if blood
sodium drops
toxicity
edema and hypertension
diet moderate in sodium is
recommended

Chloride
essential nutrient
fluid and electrolyte balance
abundant in foods (especially processed)
part of sodium chloride
rarely lacking
dehydration due to water deficiency

Potassium

maintaining fluid and electrolyte balance

affects homeostasis, such as a steady


heartbeat
found in both plant and animal cells
less found in processed foods
deficiency
hypertension
most common electrolyte imbalance
muscle weakness
toxicity
rare from food
over consumption of supplements

What Processing Does to


Sodium and Potassium Contents of Foods
Milks

Meats

Vegetables

Roast beef

Fresh corn

Chipped beef

Canned,
cream corn

Fruits

Grains

Unprocessed
Milk (whole)

Fresh peaches Rolled oats

Processed

Key:
Potassium
Sodium

Instant
pudding

Peach pie

Oat cereal

Calcium

most abundant mineral in body


bone structure, calcium bank
found primarily in milk and milk products
deficiency
limits mass & density
growing years
age related
silent, no signals

Milligrams
Food

Serving size (kcalories)

CALCIUM
As in the riboflavin figure, milk and milk products
Label(white)
dominate the calcium figure. Most people need at least three
selections from the milk group to meet recommendations.
a Values based on products containing added calcium salts;
the calcium in 12 c soybeans is about 13 as much as in
1 c tofu. b If bones are discarded, calcium declines
2
dramatically.

Key:
Breads and cereals
Vegetables
Fruits
Milk and milk products
Legumes, nuts, seeds
Meats
Best sources per kcalorie

Calcium in Selected Foods

AI for
women
1950

AI for
women
51+

AI for
men
1950

AI for
men
51+

Phosphorus
2nd most abundant
energy metabolism, transport lipids, cell
membranes
foods rich in protein, supply phosphorus

Milligrams
Food

Serving size (kcalories)

RDA
for
adults
PHOSPHORUS
Protein-rich sources, such as
milk (white), meats (red), and
legumes (brown), provide
abundant phosphorus as well.

Key:
Breads and cereals
Vegetables
Fruits
Milk and milk products
Legumes, nuts, seeds
Meats
Best sources per kcalorie

Phosphorus in Selected Foods

Magnesium

minute amount, but critical


energy metabolism, catalyst, ATP
production
critical to heart function
ingestion of hard water may reduce
incidence of heart disease
toxicity is rare, but can be fatal

Milligrams
Food

Serving size (kcalories)

RDA for
men
19-30

MAGNESIUM
Legumes (brown) are a rich
source of magnesium.

Key:
Breads and cereals
Vegetables
Fruits
Milk and milk products
Legumes, nuts, seeds
Meats

RDA for
women
19-31

Best sources per kcalorie

Magnesium in Selected Foods

Sulfur
sulfur is not used by the body
found in thiamin and several
amino acids
high sulfur content in
skin, hair, nails

Trace Minerals

iron
zinc
iodine
selenium
copper
manganese
fluoride
chromium
molybdenum

Trace Minerals
small amounts found in the body
small amounts needed
deficiency can be fatal, excess can be
deadly
TM are active in all body systems
content is dependent on soil and water
composition and processing

Iron

essential nutrient
mostly found in

hemoglobin
carrier of oxygen
myoglobin
protein in muscles, making oxygen
available
iron balance is critical
deficiency
fatigue and anemia

Iron
red meats, fish,
poultry, eggs,
legumes are good
sources

RDA for
women
1950

RDA for
women
51+

RDA
for
men

IRON
Meats (red), legumes (brown),
and some vegetables (green)
make the greatest contributions
of iron to the diet.
Key:
Breads and cereals
Vegetables
Fruits
Milk and milk products
Legumes, nuts, seeds
Meats
Best sources per kcalorie

Iron in Selected Foods

Zinc
cofactor for many enzymes affecting
growth and digestion
deficiency
growth retardation
sexual immaturity
impaired immune response
protein containing foods are a good source
of zinc

Micrograms RAE
Food

Serving size (kcalories)


RDA
for
men

RDA
for
women

ZINC
Label
Meat, fish, and poultry
(red) are
concentrated sources of zinc.
Milk (white) and legumes
(brown) contain some zinc.
Key:
Breads and cereals
Vegetables
Fruits
Milk and milk products
Legumes, nuts, seeds
Meats
Best sources per kcalorie

Zinc in Selected Foods

Iodine
converted to iodide in GI tract
essential component of thyroid hormone
regulates temperature, reproduction,
growth, cell production
deficiency
goiter: enlarged thyroid gland
cretinism
during pregnancy
irreversible mental and physical
retardation

Iodine
worlds ocean and iodized salt are best
sources

Selenium
essential antioxidant nutrient
deficiency associated with heart disease
seafood, meats, whole grains, vegetables
dependent on soil content
toxicity
loss and brittleness of hair and nails

Copper
important player in several enzyme
reactions
deficiency is rare
food sources are legumes, whole grains,
nuts, shellfish, seeds

Manganese
cofactor for many enzymes that
metabolize carbs, lipids and amino acids
deficiency is rare
too much can affect the nervous system
found in nuts, whole grains, leafy veggies

Fluoride
presence makes
bones stronger
teeth more
resistant to tooth
decay
fluoridated water is
best source
most bottled water
is lacking
too much can
damage teeth

Key:

< 49%
50% 74%
> 75%

Chromium
essential nutrient involved in carb and lipid
metabolism
maintains glucose homeostasis
deficiency
creates diabetic like symptoms
sources include liver, whole grains, yeast

Molybdenum
cofactor for many enzymes
found in legumes, cereals, organ meat

Contaminant Minerals
heavy metals
lead
mercury
cadmium
enter food through water, soil, air pollution
interfere with nutrients
bioaccumulation

Remember to eat foods, not


nutrients

The Trace Minerals

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The Trace Minerals

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The Trace Minerals


Food sources
Deficiencies
Toxicities
Interactions
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Iron
Ferrous (Fe++)
Reduced

Ferric (Fe+++)
Oxidized

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Iron Absorption

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Iron: Heme vs. Nonheme

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Iron
Factors enhance nonheme iron
absorption
MFP factor
Vitamin C
Citric acid from
foods

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Iron
Factors enhance nonheme iron
absorption
Lactic acid from foods
HCl from stomach
Sugars

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Iron
Factors inhibit nonheme iron
absorption
Phytates
Fibers
Oxalates

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Iron
Factors inhibit nonheme iron
absorption
Calcium
Phosphorus
EDTA
Tannic acid

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Iron Recycling

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Iron
High risk for iron deficiency
Women in their reproductive years
pregnant women
Infants and young children
Teenagers

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Iron
Stages of iron deficiency
Iron stores diminish
Transport iron decreases
Hemoglobin production declines

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Both size and


color are normal
in these blood
cells

Blood cells in
iron-deficiency
anemia are
small and pale
because they
contain less
hemoglobin

Iron
Contamination
iron
Iron
supplements

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Iron: In Summary
2001 RDA
Men: 8 mg/day
Women (19-50 years): 18 mg/day
Women (51+ years): 8 mg/day

Upper level for adults: 45 mg/day

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Iron: In Summary
Chief functions in the body
Part of the protein hemoglobin, which
carries oxygen in the blood
Part of the protein myoglobin in
muscles, which makes oxygen
available for muscle contraction
Necessary for the utilization of energy
as part of the cells metabolic
machinery
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Iron: In Summary
Significant sources
Red meats, fish, poultry, shellfish,
eggs
Legumes, dried fruits

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Iron: In Summary
Deficiency symptoms
Anemia: weakness, fatigue,
headaches
Impaired work performance and
cognitive function
Impaired immunity
Pale skin, nailbeds, mucous
membranes, and palm creases
Concave nails
Inability to regulate body
temperature
Pica
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Iron: In Summary
Toxicity symptoms
GI distress
Iron overload: infections, fatigue,
joint pain, skin pigmentation, organ
damage

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Zinc
Roles
Metalloenzymes

Absorption
Metallothionein

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Zinc
Enteropancreatic circulation

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Zinc
Zinc supplementation

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Zinc: In Summary
2001 RDA
Men: 11 mg/day
Women: 8 mg/day

Upper level for adults: 40 mg/day

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Zinc: In Summary
Chief functions in the body
Part of many enzymes
Associated with the hormone insulin
Involved in making genetic material
and proteins, immune reactions,
transport of vitamin A, taste
perception, wound healing, the
making of sperm, and the normal
development of the fetus

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Zinc
Significant
sources
Proteincontaining
foods
Red meats,
shellfish
Whole grains

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Zinc
Deficiency
symptoms
Growth
retardation,
delayed sexual
maturation,
impaired immune
function, hair loss,
eye and skin
lesions, loss of
appetite
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Zinc: In Summary
Toxicity symptoms
Loss of appetite, impaired immunity,
low HDL, copper and iron deficiencies

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Iodine
Iodine vs. iodide
Deficiency
Goitrogens

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Iodine: In Summary
2001 RDA for adults: 150 g/day
Upper level: 1100 g/day
Chief functions in the body
A component of two thyroid
hormones that help to regulate
growth, development, and metabolic
rate

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Iodine: In Summary
Significant sources
Iodized salt, seafood, bread,
dairy products, plants grown in
iodine-rich soil and animals fed
those plants

Deficiency disease
Simple goiter
Cretinism

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Iodine: In Summary
Deficiency symptoms
Underactive thyroid gland, goiter
Mental and physical retardation in
infants (cretinism)

Toxicity symptoms
Underactive thyroid gland, elevated
TSH, goiter

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Selenium
2000 RDA for adults: 55 g/day
Upper level for adults: 400 g/day
Chief functions in the body
Defends against oxidation
Regulates thyroid hormone

Significant sources
Seafood, meat
Whole grains, vegetables (depending
on soil content)
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Selenium
Deficiency symptoms
Predisposition to heart disease
characterized by cardiac tissue
becoming fibrous (Keshan disease)

Toxicity symptoms
Loss and brittleness of hair and nails
Skin rash, fatigue, irritability, and
nervous system disorders
Garlic breath odor

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Copper
2001 RDA for adults: 900 g/day
Upper level for adults:
10,000 g/day (10 mg/day)
Chief functions in the body
Necessary for absorption and use of
iron in the formation of hemoglobin
Part of several enzymes

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Copper
Significant sources
Seafood
Nuts, whole grains, seeds, legumes

Deficiency symptoms
Anemia, bone abnormalities

Toxicity symptoms
Liver damage

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Manganese
2001 AI
Men: 2.3 mg/day
Women: 1.8 mg/day

Upper level for adults: 11 mg/day


Chief functions in the body
Cofactor for several enzymes

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Manganese
Significant sources
Nuts, whole grains, leafy vegetables,
tea

Deficiency symptoms
Rare

Toxicity symptoms
Nervous system disorders

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Fluoride
1997 AI
Men: 3.8 mg/day
Women: 3.1 mg/day

Upper level for adults: 10 mg/day


Chief functions in the body
Involved in the formation of bones
and teeth
Helps to make teeth resistant to
decay
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U.S.
Population
With
Fluoridated
Water

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Fluoride
Significant sources
Drinking water (if fluoride containing
or fluoridated)
Tea, seafood

Deficiency symptoms
Susceptibility to tooth decay

Toxicity symptoms
Fluorosis (pitting and discoloration of
teeth)
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Chromium
2001 AI
Men: 35 g/day
Women: 25 g/day

Chief functions in the body


Enhances insulin action

Significant sources
Meats (especially liver)
Whole grains, brewers yeast

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Chromium
Deficiency symptoms
Diabetes-like condition

Toxicity symptoms
None reported

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Molybdenum
2001 AI for adults: 45 g/day
Upper level for adults: 2 mg/day
Chief functions in the body
Cofactor for several enzymes

Significant sources
Legumes, cereals
Organ meats

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Molybdenum
Deficiency symptoms
Unknown

Toxicity symptoms
None reported
Reproductive effects in animals

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Other Trace Minerals


Nickel
Silicon
Vanadium

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Other Trace
Minerals
Cobalt
Boron
Arsenic

Contaminant Minerals
Heavy metals
Lead

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Phytochemicals And
Functional Foods

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Phytochemicals And
Functional Foods

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Phytochemicals And
Functional Foods
Defending against cancer
Defending against heart disease

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Functional
foods...
from nature

from
manufacturers

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Phytochemicals And
Functional Foods
Functional foods
Inconclusive research
Food labels
Safety
Overall healthfulness of products

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Medical Chemistry (1st year)

Lecture I
MUDr. Vlastimil Kulda

Textbooks

General and Inorganic Chemistry for Medical Students


Basic Organic Chemistry for Medical Students
Medical Chemistry Laboratory Manual

Web pages

Faculty of Medicine in Pilsen

www.lfp.cuni.cz
Department of Medical Chemistry and Biochemistry

www.lfp.cuni.cz/biochemie

Chemistry
- science studying the properties and behavior of matter

Matter - physical material of the universe


- anything that has mass and occupies space
States of matter: 1) gas

(no fixed volume or shape)

2) liquid

(distinct volume but no specific shape)

3) solid

(both definite shape and volume)

Pure substance matter that has fixed composition and


distinct properties (sodium chloride, water)

2 categories of substances:

Elements cannot be decomposed by chemical methods


into simpler substances (carbon, oxygen, iron)
= consist of one kind of atoms

Compounds contain two or more kinds of atoms


(water H2O sodium chloride NaCl)

Structure of the atom

atom the smallest particle of an element having


its chemical properties
("atomos" in old Greek language = "indivisible")
3 types of subatomic (elementary)
particles:
PROTONS
NEUTRONS

ELECTRONS

"nucleons"

Particle

Symbol

Relative charge

Relative mass

Proton

positive +1

Neutron

Electron

negative -1

negligible *

relative mass expressed in "atomic mass units"

(relative atomic mass, relative molecular mass)


atomic mass unit = 1/12 of the mass of an atom of the carbon isotope 12C
(1.66 x 10-24 g)

* mass of the electron = only 1/1836 of the mass of the proton

Atoms have no overall charge


==>

number of protons = number of electrons


This number is different for every element !

= ATOMIC number ( Z )
Element = mixture of atoms with the same number of protons
(the atomic number)
The chemical properties of any given element are determined by
the arrangement of electrons around the nucleus.

Every atom is characterized by 2 numbers:

Atomic number (Z)

= number of protons

- it determines the element = symbol: C, N, Fe

Mass (nucleon) number (A)

= number of nucleons
(protons + neutrons)

mass number
atomic number

12
6

symbol of element

Nuclide - specific atomic number Z and mass number A


for example:

12
6C

238
92

- most elements are mixtures of different nuclides !


(same atomic number, different mass numbers)
= same number of protons, variation in number of neutrons

= ISOTOPES of an element
------------------------------------------------------------------Term "nuclide" - more general
- used: only one nucleus or several nuclei of different elements
Term "isotope" - used when referring to several different nuclides of the same
element

Isotopes of hydrogen

neutrons

proton

1
1

2
1

hydrogen

3
1

deuterium (D)

tritium (T)

The isotopes of an element have a different number of NEUTRONS


-identical chemical properties

water

H2O

"heavy water"

D2O

Isotopes of carbon
12
6

13
6

14
6

------------------------------------------------------------------------------------------------

Certain isotopes of some elements are radioactive !


Radioactive decay = unstable atomic nucleus "loses energy" by emitting:
particle

4
2

particle

0
-1

g
14
6

half life 5730 years

14
7

He
e

rays ( = high-energy photon)


0
-1

+ antineutrino

Electrons
- surround the nucleus in energy levels (shells, orbits)

1 electron

6 electrons

15 electrons

The chemical reactions = interaction of electrons

from the OUTERMOST orbit

Arrangement of electrons in the atom


4 quantum numbers:
1) n

principle quantum number

- determines energy level


- positive integral values 1, 2, 3, 4, ...
K, L, M, N, ...

2) l

orbital quantum number

- determines the shape of electron cloud


- values from 0 to (n-1) 0, 1, 2, 3, ...
s p d f

3) m

magnetic quantum number

- determines orientation of electron cloud


in space
- integral values from l to +l

4) s

spin

- determines the intrinsic state of an electron


- only 2 possible values: + or -

The s orbitals

orbital quantum number


l=0
magnetic quantum number m = 0 (only possib.)
in each s orbital can be only 2 electrons
(with different SPIN)

1s

1s1

1s

1s2

spherical

The p orbitals

two lobes

orbital quantum number


magnetic quantum number

l=1
m = -1

in each p orbitals can be 2 x 3 = 6 electrons

2p

2p2

2p

2p6

The d orbitals

orbital quantum number


magnetic quantum number

l=2
m = -2 -1

in each d orbitals can be 2 x 5 = 10 electrons

3d

3d7

Rules that must be respected


1) The lowest energy levels are
occupied first.
2) Hunds rule:
No electron pairing in p, d, f
orbitals until each orbital of given
set contains one electron.
3) Pauli exclusion principle:
No TWO electrons in any given
atom can have exactly the same
set of all 4 quantum numbers.

Electron configuration of several elements


Electrons

Orbital diagram

1s2 2s1
1s2 2s2
1s2 2s2 2p1

1s2 2s2 2p2


1s2 2s2 2p3
1s2 2s2 2p6

1s2 2s2 2p6 3s1

The periodic properties of the elements


The elements with similar arrangement (configuration) of electrons

in the outer (superficial) shell have SIMILAR CHEMICAL PROPERTIES

Periodic table
Dmitri Mendeleyev (1869) - Russian chemist
- elements are listed in order of increasing atomic number
horizontal rows = PERIODS
vertical columns = GROUPS
elements in groups: the same number of electrons in outermost orbits

= similar chemical properties

Names for some of the groups


Group

Name

Elements

IA

Alkali metals

Li, Na, K, Rb, Cs, Fr

II A

Alkaline earth metals

Be, Mg, Ca, Sr, Ba, Ra

VI A

Chalcogens

O, S, Se, Te, Po

VII A

Halogens

F, Cl, Br, I

Noble (rare, inert) gases

He, Ne, Ar, Kr, Xe, Rn

VIII A (0)

Chemical bonding
Covalent bond

- sharing of one or more pairs of electrons

Coordinate covalent bond - both electrons of the bond belong to one


atom, the other has empty orbital

Ionic bond - big difference of electronegativities


- IONS attracted by electrostatic forces

Na+ Cl-

Hydrogen bonding
a weak electrostatic interaction between partly (+) charged hydrogen
atom and partly (-) charged another atom (O, N, F)
R
N
R

H bonds

(+)
(-)
H ............. O

R
C

vodkov mstek

important in stabilizing the structures of: PROTEINS


NUCLEIC ACIDS

The EARTH

Core (inner, outer)


Mantle

Crust
Crust
Lithosphere
Hydrosphere
Atmosphere
Biosphere

93 %
7%
0.03 %
0.001 %

The elementary composition (%)


Earth crust

Human body

49.5

62.4

Si

25.7

Al

7.5

Fe

4.7

0.005

0.9

9.8

0.12

1.0

0.09

21.1

0.06

0.16

0.03

3.1

- elementary composition of the human body is very different


from that of lithosphere

Specific selection of some elements for the biological uses


% in human body
% in the Earth crust
C

243

103

11

2.7

1.26

Fe

0.001

Al

0.000 13

Si

0.000 04

- some chemical elements (C, H, N, O, ...) are "better" than


others to make up molecules of living organisms

- most abundant elements of the Earth core:

Fe, Ni

- most abundant elements of the Earth crust:

O, Si, Al, Fe

- most abundant elements in living organisms:

O, C, H, N

- oxygen is the most abundant element both on the Earth surface


and in human body

The atmosphere of the Earth

Composition of the AIR


Water vapour

1-4%

The dry air (by volume)


Nitrogen
Oxygen
Argon
Carbon dioxide
All others

78 %
21 %
0.93 %
0.038 %
only trace amounts

The geological development of the atmosphere


the loss of very light gases ( H2
the increase of O2

20th centrury - slight increase of CO2

burning of coal, gas, oil


destruction of forests and phytoplankton

current levels

0.0296 %
0.0385 %

CH4 )

(photolysis of water by the green plants)

fixation of CO2 by photosynthesis

1900

He

296 ppm
385 ppm

The greenhouse effect


CO2 is a "greenhouse gas" - global warming

The oxygen cycle


O2
Animals, plants
RESPIRATION

CO2
H2O
We need per day:

air
water
food

Plants
PHOTOLYSIS of H2O
PHOTOSYNTHESIS

15 000 l [ 13.5 kg ]
2 kg
1.2 kg

Comparison of inspired and expired air


Inspired

Expired

O2

21 %

15 %

CO2

0.03 %

5%

N2

78 %

78 %

CO2 is a waste product


of respiration

Air pollution
Emissions = the pollutants released into the environment
Pollution

natural
industrial

Natural sources
Volcano eruptions
Dust storms
Fires
Lightnings
Biological decomposition

dust
dust
dust
NO
CO2

ash

SO2

ash CO2 CO
NO2
H2S NH3 CH4

Dust particles water condensation CLOUDS, RAIN


Impact of big meteor heavy dust pollution of atmosphere
climate changes
( extinction of giant reptiles in mesozoic era ? )

Industrial sources
The progress of civilization global air pollution
(overcharging of the natural cycles of regeneration and detoxication)
1)
2)
3)
4)
5)
6)

dust ashes
Sulphur dioxide ( SO2 )
Nitrogen oxides ( NOx )
Carbon oxides ( CO2 CO )
Toxic metals
Organic compounds

Particulate matter - dust, ashes


complex mixture of extremely small particles and liquid droplets
sources: power plants, industrial and agriculture processes, transport, home
effects: irritation of respiratory system
contains adsorbed number of components: toxic metals, SO2
cancerogenic hydrocarbons
the size of particles is directly linked to their potential for causing
health problems - smaller than 10 m pass through the airways
and enter the lung !
SMOG [ smoke + fog ]

"London smog"

HELP: industry, power plants - electrostatic precipitation


home - no burning of coal and peat
- using gas or oil, solar energy
Limit: 150 g / m2 /year

Sulphur dioxide

SO2

main source: burning of soft coal ( 1 % S as sulphides of Fe )


Europe 1980: 40 000 000 tons of SO2

( bound to fly ash )

irritation of respiratory system, rhinitis, laryngitis


SO2 + H2O H2SO3
SO2

SO3 + H2O H2SO4

sulphurous acid (weak acid)


sulphuric acid

(strong acid)

ACID RAIN
pH ~ 4
acidification of soil solution of minerals Al3+ Pb2+ Cu2+ ...
intoxication of plants and animals
green plants: CO2 x SO2 competition destruction of photosynthetic enzymes
(damage of pine forests)

Sulphur dioxide

SO2

"Safe" limit: 0.15 mg / m3


Short time limit (up to 30 min./day) 0.5 mg / m3

HELP: Power plants: soft coal + CaCO3

CaSO4 ("gypsum")

OR
SO2

+ Ca(OH)2 CaSO4

Acid soil: + CaCO3


+ Ca(OH)2

("limestone")
("lime water")

Nitrogen oxides
NO

NOx

limit: 0.1 mg / m3

NO2

brown haze

sources: motor vehicles, power plants, chemical industry


secondary pollutants:

OZONE ( O3 )
PAN = peroxyacylnitrates

sun light

NO2

NO + O

Photochemical smog
( "Los Angeles type" smog )

O2 + O

O3

O3 + hydrocarbons

aldehydes

(car exhausts)
+ NO2

PAN

very irritating to eyes


and respiratory system

"London type" smog


combustion of coal

= smoke + fog

emission of sulphur dioxide ( SO2 ) and dust

+ mixed with FOG

"Los Angeles type" smog


dry air + sunny days
+ NOx
+ volatile organic gases

(emitted by automobiles)

= photochemical smog

Carbon dioxide CO2


colorless, odorless gas
"overproduction" sources: burning of fossil fuels
air: 0.038 %
higher levels stimulate breathing
long time respiration of 5 % CO2 respiration troubles
> 15 % DEATH
Danger: old mines, caves, wine cellars
(heavier than air it tends to go down)

Carbon monoxide CO
colorless, odorless gas
sources: car exhausts, incomplete burning (smouldering)
local street pollution dangerous level: 10 ppm / 8 hours
TOXIC: very high affinity to HEMOGLOBIN

35 ppm / 1 hour

carbonylhemoglobin

impaired ability of the blood to transport O2 oxygen deprivation


drowsiness unconsciousness DEATH

Toxic heavy metals


Lead

Pb

- tetraethyllead was used as antiknock agent in gasoline


(organometallic compound)

Pb (CH2CH3)4
neurotoxic

PbO (lead oxide aerosol)


deposition in the vicinity of highways

toxic effects of inorganic lead compounds: impaired heme synthesis anemia

Toxic metals aerosol As, Pb, Cd, Hg, ... oxides bound to ash particulate matter
- source: power plants ( COAL ! ), smelters
- general toxicity decrease of vitality

Organic compounds
Hydrocarbons motor vehicles, industry, cigarette smoke ( TAR )
- carcinogens, precursors to PAN

Freons - hydrocarbons with hydrogen atoms substituated by F, Cl


= chlorofluorocarbons ( CFCs )
- in older refrigeration and air-conditioning systems
- effect: destroying the ozone layer in the stratosphere

Indoor air pollution


Respiration CO2

( H2O)

Digestion (intestinal bacteria) H2S


Gas stove CO2

CO

indole

( H2O)

Tobacco smoke TAR (cancerogens)

Formaldehyde

Radon

Rn

HCHO

nicotine

- released from foamed insulation


tapestry
plywood adhesives

- radioactive gas
- radon from natural sources can accumulate in buildings
222

86

Rn

4
2 He

218
84

Po

Water
non-bonding electron pairs

H2O

105o

bent molecule
d-

polar character

O
H
d+

d+

electrical dipole

Hydrogen bonding
-

attractions between water molecules

+
+

0 oC

3.6

/ H2O

HIGH melting point


boiling point
specific heat
heat of vaporization
surface tension

H bonds - much weaker than covalent bonds !


bond energy of H-bonds in liquid water: about 19 kJ/mol
( covalent H O bond in water: 460 kJ/mol )
water is most dense at 3.98 C !!!

(when freezing, ice will form first on the surface)

WATER - very good solvent !


Attraction between
water dipoles and ions

"hydrated ions"

Dispersing "amphipathic" molecules

"micelles"

"Amphipathic" molecules contain both highly hydrophobic


and highly polar groups

palmitic acid
non-polar chain = hydrophobic

polar group = hydrophilic

(water-fearing)

(water-loving)

Phospholipids
phosphatidylcholine
(lecithin)

polar groups

Water in human body


~ 60 % of the body weight
intracellular ~ 40 %
extracellular ~ 20 %

PLASMA
5%
interstitial fluid 15 %

- a very complex solution of inorganic & organic components


Phosphates
Proteins

K+

Na+ Mg2+

Na+
Cl-

Na+

K+

Ca2+

HCO3-

Mg2+

Phosphates

K+

Na+/K+ pump

( = Na+/K+ -ATPase )

Blood plasma
( extracellular fluid )

Cell fluid (cytosol)


( intracellular fluid )

Human blood plasma


mmol/l
Na+

132 145

K+

3.8 - 5.2

Ca*

2.1 2.6

Mg2+

0.8 1.1

Cl-

97 108

HCO3-

22 26

Phosphates
HPO42- + H2PO4-

0.6 1.6

pH = 7.36 7.44
* Ca "total Ca"

Ca2+ "ionized" is about of "total" ~ 1.2 mmol/l

Colligative properties of solutions


- dependent on the number of solute particles

the same effect


Effects of a solute on a solvent:
depression of the freezing point
elevation of the boiling point
depression of the vapour pressure
osmotic pressure
osmolality = moles of solute particles dissolved in 1 kg of solvent
( osmolality of blood plasma: 285 mmol/kg )

Water balance
Intake: ~ 1.5 - 2.0 l / day
metabolic water (produced in human body by oxidation of food) 0.3 0.5 l /day
Resorption: stomach, small intestine, LARGE INTESTINE
Secretion:

Excretion:

Saliva
Stomach
Bile
Pancreas
Small intestine

1 500 ml / day
2 500
500
700
3 000

Urine 60 %
Skin
20 % (perspiration)
Lungs 15 %
Faeces 5 %

8 200 ml /day

Water in nature
Hardness of water:
Temporary hardness:

Boiling:

technical problems deposits after boiling


cause = Ca(HCO3)2

Ca(HCO3)2

soluble in water

CaCO3 + CO2

+ H2O

Softening water in water stations:

Ca(HCO3)2 + Ca(OH)2

2 CaCO3 + 2 H2O

Permanent hardness: cause = CaCl2 CaSO4 ...


softening: CaSO4 + Na2CO3

CaCO3 + Na2SO4

Biological pollution of water


urine, excrements, dead bodies
BACTERIAL decomposition (most efficiently by aerobic bacteria)
I. organic compounds: UREA, proteins, peptides
II. NH3
III. NO2-

markers of
RECENT pollution

ammonia
NO3-

- final decomposition products


- good for plant nutrition

EUTROPHICATION of water

- fertilizers, phosphates
(compounds of N, P)

The bioelements (summary)


1)

Principal bioelements:
O, C, N, H, P, S
( biomolecules: proteins, nucleic acids, lipids, saccharides )

2)

Water and ions ( H2O ) Na+, K+, Mg2+, Ca2+, Cl-, ( HCO3- , phosphates)

3)

Mineral constituents of bones and teeth Ca (Mg, Na)


PO43- CO32- ( F- Cl- )

4)

Microelements (trace elements)

Fe, Cu, Co, Zn, I, F, Se, ...

-------------------------------------------------------5)

Contamination (intoxication):

Hg, Al, ...

Medical Chemistry (1st year)

Lecture II
MUDr. Vlastimil Kulda

Biological membranes
- separate the cells

separate the spaces (compartments) of the cell

cell membrane
mitochondria
nucleus
lysosome

endoplasmic reticulum

Phospholipid BILAYER
hydrophilic
hydrophobic
hydrophilic

phospholipids
cholesterol
PROTEINS - enzymes

SELECTIVE permeability
(membrane = barrier)

- receptors
- transport systems

The flow of molecules and ions between the cell and environment is
precisely regulated by SPECIFIC TRANSPORT SYSTEMS
They regulate cell volume, ionic composition, pH
They concentrate metabolic fuels and building blocks from the environment
The extrude toxic substances
They generate IONIC GRADIENTS essential for the excitability

Transport across membrane


1) Passive transport
"channels"

2) Active transport
"pumps"

- does not involve energy


- diffusion from high to low concentration

- uses energy (ATP)


- can transport against the concentration gradient
- one direction, high specificity

ATP

3) Secondary active transport - no direct need of energy


- gradient created by active transport is used !

Passive transport
concentration and
electrochemical
GRADIENT
1

1) Simple diffusion

toward equilibrium

small molecule, NO charge, solubility in lipids !

O2

CO2

2) Ion channels - pore-forming proteins


- can be "GATED"
"gate" is closed

3) Facilitated diffusion ("carrier proteins")

"gate" is open

- selective !

- large molecules, insoluble in lipids

Ion transport antibiotics


Gramicidin

- peptide: 15 amino acids

HELIX - hydrophilic groups inside


"wet channel"
- lipophilic groups outside

increase of the permeability of bacterial cell wall


inorganic ions can travel through
equilibration of concentrations = NO GRADIENT

"wide wet pore"

Valinomycin
hydrophillic groups INSIDE = "WET cave"
hydrophobic (lipophillic) groups OUTSIDE
( = soluble in lipids of membrane)

K+

highly selective carrier for

K+

K+

( Na+ with water coating is too big)

equilibration of K+ concentration = NO GRADIENT

K+

Valinomycin
hydrophillic groups

hydrophobic (lipophillic) groups

Active transport = PUMPS


Transport against
GRADIENT

ENERGY !

ATP

ADP + Pi

Na+/K+ ATPase
(sodium potassium pump)

ATP

INHIBITION:

cardiotonic steroids

2 K+

3 Na+

Na+/K+ ATPase
in cell membrane of EVERY human cell !
electrogenic = transfers 3 Na+ out and ONLY 2 K+ into the cell
inner side of the membrane

inhibitors of this pump:

outer side of the membrane

cardiotonic steroids = cardiac glykosides


(oubain, digoxin)
treatment of heart failure, cardiac arrhytmia

Digitalis purpurea
(foxglove)

H+/K+ ATPase
stomach gastric acid
CO2

HCl

CO2 + H2O
*
H2CO

* carboanhydrase Zn2+
HCO3-

H+ Cl-

K+

ATP

HCO3- + H+

Clblood pH = 7.4

parietal cell

107 increase of H+ concentration !

lumen of the stomach


pH = 1 - 2

Secondary active transport

"COTRANSPORT"

Na+ dependent transport of glucose, aminoacids, Ca2+


"energy" = Na+ gradient generated by Na+/K+ ATPase

Na+
glucose

SYMPORT

ANTIPORT

Na+
Ca2+

Na+ - glucose symport

glucose

glucose

Na+

K+

Na+
ATP

proximal tubulus of each nephron in the kidneys resorption of glucose


intestines resorption of glucose from GI tract

Na+/Ca2+ antiport = sodiumcalcium EXCHANGER

Ca2+

Ca2+

Na+

K+

Ca2+ ATPase
Na+/Ca2+ exchanger

Na+
ATP

very low concentration of Ca2+ in cytosol

Endocytosis
Large (polar) molecules cannot pass through the hydrophobic membrane
phagocytosis - cell ingests large object such as bacteria
pinocytosis - uptake of solutes and molecules such as proteins
receptor-mediated endocytosis specific !

LDL receptor

chylomicron remnant receptor


receptors that mediates endocytosis of
blood plasma lipoproteins

cell absorbs material by engulfing it with its own membrane

Exocytosis
= the opposite of endocytosis
Exocytosis is needed for:
- secretion of large molecules from cells: glands peptide hormones
B cells antibodies

- neuronal chemical synapses: realease of the neurotransmitter


receptor

vesicles with
neurotransmitter

synaptic cleft

Water transport across membranes


Water moves by "simple diffusion" through membranes

Additional mechanism for water transport:

AQUAPORINS
"water channels"

Water transport - due to osmotic differences (osmotic gradient)

OSMOSIS
high osmolality

H2O

low osmolality

The bioelements (summary)


1)

Principal bioelements:
O, C, N, H, P, S
( biomolecules: proteins, nucleic acids, lipids, saccharides )

2)

Water and ions ( H2O ) Na+, K+, Mg2+, Ca2+, Cl-, ( HCO3- , phosphates)

3)

Mineral constituents of bones and teeth Ca (Mg, Na)


PO43- CO32- ( F- Cl- )

4)

Microelements (trace elements)

Fe, Cu, Co, Zn, I, F, Se, ...

-------------------------------------------------------5)

Contamination (intoxication):

Hg, Al, ...

Elements of group I
IA

Alkali
metals

IB

Hydrogenium

Cu

Cuprum

Li

Lithium

Ag

Argentum

Na

Natrium

Au

Aurum

Kalium

Rb
Cs
Fr

Alkali metals - very reactive

- react with air O2 and H2O


- must be stored under oil

Hydrogen

biogenic element - it is present in almost all organic compounds !


H2O

H+ = proton ( H3O+ )
pH = - log [H+]
The pH scale

acidic solutions

7
neutral

alkaline (basic) sol. 14

water is weakly ionized:

H+ + OH-

H2O

KW = [H+] x [OH-] = 10-14 mol2 / l2

ionic product of water

pH + pOH = 14
pure water: [H+] = [OH-] = 10-7 mol/l

pH = pOH = 7

----------------------------------------------------------------------Strong acids - fully ionised: monobasic acid: HCl


dibasic acid: H2SO4

Weak acids do not disociate completely:


Strong bases: NaOH, KOH, Ca(OH)2
Weak base: NH4OH

CH3COOH

H+ + Cl2 H+ + SO42H+ + CH3COO-

human blood plasma:

pH = 7.40

+
-

0.04

gastric juice: pH = 1 2
pancreatic juice: pH = ~ 8
----------------------------------------------------H+

very low concentration in blood plasma !!!

pH = 7.40

H+ = 0.000 040 mmol/l (40 nmol/l)


(Na+ 142 mmol/l
K+ 4.5 mmol/l)

extreme influence of H+ on biological systems !!!


ionisation of functional groups in PROTEINS

Ionisation of amino acids

Lithium
compounds:

LiCl

Li2CO3

Li
crimson (red) colour of flame

Therapy of manic-depressive psychosis (bipolar affective disorder)


= alternating periods of mania (euphoria) and depression
The manic phase

- increased activity, decresased need for sleep


- persistent elevated mood
- impaired normal functioning !

The depressive phase - lack of energy


- pessimistic
- self-destructive behavior (risk of suicide !)

Li+ changes of ion transport in CNS

- still in use

"mood stabilizing agent"

Lithium mineral water therapy of GOUT (type of arthritis)


(Li-urate more soluble than uric acid)

Uric acid - in humans - the end product of purine catabolism


OH
N

N
HO

OH

NH

- poorly soluble in water


- lithium urate more soluble !

Sodium
Na+

Na

(Natrium)

the main EXTRAcellular cation

(132 145 mmol/l)

Na+ strongly binds water


ionic diameter: Na+
K+
!!! in hydrated form: Na+ larger in diameter than K+

Na+ ( together with Cl- ) large fraction of osmotic pressure (osmolality)


of body fluids

Water and Na balance are closely interdependent !

NaCl

daily intake: 5 15 g

Elimination:

urine (95 %)
sweat (perspiration)
stool

food (common salt)

Kidney
Glomerular
filtration

BLOOD

Glomerular filtrate (180 l H2O / day)


[ 1.5 kg NaCl ]

Tubular
resorption
dependent on hormones
(aldosteron, ADH)

URINE
2 l H2 O
5 15g NaCl

Hormones regulating tubular resorption


Aldosteron

- steroid hormone (mineralocorticoid)


- produced in the adrenal gland (adrenal cortex)
- acting in the distal tubule of the kidney nephron:
reabsorption of Na+ into blood
secretion of K+ into urine

Vasopressin = antidiuretic hormone (ADH) - peptide hormone


- synthesized in the hypothalamus, released into
blood in the pituitary gland (posterior part)
- ADH increases the permeability of the collecting duct to water

allows water reabsorption small volume of concentrated urine


deficiency of ADH: DIABETES INSIPIDUS - polyuria

- excretion of large amounts of diluted urine ( 10 20 l /day !)

Potassium
K+

the main INTRAcellular cation

(Kalium)
(cytosol > 100 mmol/l)

- human blood plasma: only 3.8 - 5.2 mmol/l


- daily intake: ~ 4g of KCl
excretion: URINE
-

proper concentrations of K+ and Na+ functions of membranes


"membrane potential"
most cells membrane potential relatively stable
neurons, muscle cells use changes of membrane potential for function !
(nervous system communication between neurons)
action potential

Na+/K+ ATPase
EXTRAcellular fluid
cell membrane
INTRAcellular fluid

3Na+

2K+

Ion channels

Na+

ATP !

2K+

K+

rising phase = depolarisation

ACTION POTENTIAL

falling phase = repolarisation

resting potential

In cells K+ is bound to GLYCOGEN !


Diabetic coma

glucose in blood )

insulin

Glycogen synthesis

Binding of K+ in cells

Plasma K+ depletion

HEART failure !!!

Copper

Cu

(Cuprum)

microelement (in human body 100 - 150 mg)


dietary intake: ~ 2 mg / day
Cu2+ - cofactor of some enzymes:

cytochrom c oxidase
(metalloenzymes)
superoxide dismutase
- cofactor of HEME biosynthesis

CERULOPLASMIN - transport of Cu2+ in blood plasma ( 8 Cu2+ / mol. )


- a2 globulin synthesized in the liver
- enzymatic activity: Fe2+ Fe3+
WILSONs DISEASE
(hepatolenticular degeneration)

- accumulation of copper in tissues


- low ceruloplasmin levels
- hereditary disease
- neurological symptoms, liver disease

CuSO4 . 5 H2O

copper (II) sulphate pentahydrate


= "blue vitriol"
- in Fehlings solution (detection of glucose in urine)

copper salts - poisonous !


-------------------------------------------

Hemocyanins - Cu2+ containing proteins


- O2 transport - MOLLUSCA (snail, clam, mussel, ...)
- ARTHROPODA (crabs)

Silver
precious metal

Ag
( + H 2S

(Argentum)
Ag2S black ! )

AgBr - photosensitive photography


------------------------------------------------------------------

Ag - useful in dental alloys for fittings and fillings


( Ag + Hg amalgam )

AgNO3 - caustic effect treatment of warts


Bartholins gland abscess in women
(removal: silver nitrate stick insertion)

- diluted solution: antiseptic properties it was dropped into newborns eyes


to prevent gonococcal conjuntivitis !
(Gonorrhoea is a venereal disease caused by the bacteria Neisseria gonorrhoeae)

Gold
precious metal

Au

(Aurum)

chemically and biologically resistent, inert

in nature almost exclusively in the native state


pure gold soft !

in jewellery: alloys (+ Cu, + Ag) harder


The gold content of gold alloys

in carats or in thousandths
pure gold: 24 carats = 1000/1000
The standard for high quality jewellery: 18 carats = 750 / 1000
What is the gold content (g) of a 100 g piece marked 18 carats?
18
24

x 100g = 75 g

Elements of group II
II A

Alkaline
earth
metals

II B

Be

Beryllium

Zn

Zincum

Mg

Magnesium

Cd

Cadmium

Ca

Calcium

Hg

Hydrargyrum

Ba

Barium

Sr

Strontium

Ra

Magnesium

Mg

PLANTS: Mg2+ - central atom of green pigment CHLOROPHYLL


(photosynthesis)
in human body: ~ 20 g Mg
> in bones ( Ca-Mg phosphates )
intracellular cation
Mg2+ activates number of enzymes !!!

ENZYMES using ATP


"kinases"

hexokinase
glucose

glucose6phosphate

ATP

ADP

(Enzymes of ATP-dependent reactions require Mg2+ as cofactor)

other effects of Mg2+:

anti-convulsive effect
(MgSO4 - prevention of eclamptic convulsions)
influence on neuromuscular excitability
can help to prevent kidney and gall stones

"duodenal reflex" - MgSO4 delivered into the region of the sphincter of Oddi
relaxation of the sphincter + contraction of the gallbladder
expulsion of bile to intestine

( the bile release from the gallbladder is stimulated by Mg2+ )


Magnesium mineral water (Karlovy Vary) purgative effect

Calcium
CaCO3

"burning"

limestone,
chalk

CaO + H2O

Ca
CaO + CO2
quicklime

"slaking"

Ca(OH)2
slaked lime

Hardening of mortar:

Ca(OH)2 + CO2

CaCO3 + H2O

Calcium

Ca

in human body ~ 1 kg (99% in bones, teeth)


dietary intake: 800 - 1200 mg / day
human blood plasma: "total Ca"
(extracellular !)
ionized Ca2+

2.5 mmol/l
1.2 mmol/l

resorption: ileum specific protein carrier


~ 200 mg / day

excretion: urine
liver

bile

feces

Mineral constituents of bones and teeth


Ca
PO43Hydroxyapatite
Ca5 (PO4)3 OH

Ffluoroapatite

enamel
dentin

cementum
pulp

Enamel: - hardest substance of the body


water
1-3 %
organic comp.
1%
mineral
> 95 %

(bones ~ 60 %)

Hormones regulating Ca metabolism


Parathormone - peptide hormone ( 84 amino acids )
- secreted by parathyreoid glands

PTH

- activation of bone mineral degradation


Ca2+ release from bones
- stimulation of Ca2+ readsorption in kidney
- stimulation of calcitriol formation (kidneys)
- stimulation of Ca-resorption protein formation (ileum)

Ca2+

in blood

Calcitonin

- peptide hormone ( 32 amino acids )


- produced by parafollicular cell of the thyreoid gland
- inhibition of bone mineral degradation
(decrease of osteoclasts activity)
- stimulation of Ca2+ excretion in kidney

Ca2+

in blood

Salmon calcitonin is used for the treatment of OSTEOPOROSIS

Calcitriol

= 1,25-dihydroxycholecalciferol
- active form of Dvitamin

- stimulation of Ca-resorption protein formation

absorption of calcium from the gastrointestinal tract

PTH

Ca FOOD (protein-bound)
ILEUM
Ca-resorption protein

calcitriol

calcitonin

PLASMA
BONES
PTH

PTH
URINE

Ca 2.5 mmol/l
Ca2+ 1.2 mmol/l

calcitonin

calcitriol
milk
excrements

Ca2+ increase

PTH release inhibition

Very low concentration of Ca2+ in cytoplasma

10-6 mol/l

MUSCLE - Ca2+ is stored in sarcoplasmic reticulum (SR)

CALSEQUESTRIN = calcium-binding protein of the SR


40 Ca2+ binding sites
Ca2+ in cytoplasma can cause the specific action of the cell:

MUSCLES contraction

Ca2+ = important SECOND MESSENGER

endoplasmic reticulum

SIGNAL

release of Ca2+
EFFECT

Clotting of BLOOD
Intrinsic pathway

Extrinsic pathway

(Contact activation pathway)

(Tissue factor pathway)

Xa
Prothrombin

Thrombin
Fibrinogen

Fibrin

Ca2+ is required for the proper function of the coagulation CASCADE

Removing of Ca2+ = NO clotting !


Anticoagulants - bind Ca2+ ions
( "in vitro" = outside the body)

Oxalate

COO COO -

Citric acid

Ca2+

COO

Ca

COO

EDTA = ethylenediamine tetraacetic acid

Gypsum, plaster of Paris

CaSO4 . 2 H2O

heating

CaSO4 . 1/2 H2O


+ H 2O
hardening

CaSO4 . 2 H2O
When the dry plaster powder is mixed with water, it re-forms into gypsum
bandage impregnated with plaster = support for broken bones

Strontium Sr
- similar to Ca2+ incorporation in BONES
(naturally present in bones in trace amounts)
- new treatment for osteoporosis: "Strontium ranelate"
(improves bone density and strenght)

excess: Strontium rickets


radioisotope

90

Sr

bone marrow irradiation

LEUKEMIA

half life 28 years

(important isotope regarding health impacts after the Chernobyl disaster)

radioisotope

89

Sr

half life 50 days

- treatment of bone cancer

Barium Ba
toxic heavy metal
water-soluble compounds
[ Ba(NO3)2 BaCl2 ]

- strongly neurotoxic
- painful cramps, tremor

BaSO4 (barium sulphate)


- almost insoluble in water !
- radiocontrast agent for X-ray imaging
( "barium meal" )
- imaging of the gastrointestinal tract
large intestine

Zinc
microelement

Zn

(Zincum)

dietary intake: 12 -15 mg / day

cofactor of many ENZYMES:


carboxypeptidase - protein digestion

carbonic anhydrase

H2O + CO2

H2CO3

H+ + HCO3-

alcohol dehydrogenase - oxidation of ethanol to acetaldehyde


NAD+

CH3CH2OH

NADH+H+

CH3CHO

Insulin binds ZINC !

"Zn insulin hexamers"

Metallothionein - protein synthesized in kidneys rich of -SH groups


- can bind metals ( Zn2+ Cd2+ .... )
- zinc transport, heavy metal detoxification (Hg2+) ?
Zinc is an essential nutrient for proper sperm production !
-----------------------------------------------compounds used in medicine:

ZnO - a basis of powders, pastes, creams


( in DERMATOLOGY )

dental fillings (cements):

Zn3(PO4)2 . 4 H2O

"hopeit"

Cadmium Cd
toxic heavy metal
metallothionein strongly binds Cd2+

Cd intoxication
kidney damage

"Itai itai disease" - mass Cd poisoning in Japan in 1950


- the name comes from painful screams
( "itai" in Japanese = PAIN )
- the bones become soft and weak severe pain, fractures

"Chemical castration" = destruction of seminiferous epithelium


of testicles ( Zn2+ antagonism )

Mercury Hg (Hydrargyrum)
Toxic effects
1) elemental Hg

- very toxic when absorbed as a vapour through lungs


- poorly absorbed through the gastrointestinal tract !!!
(only purgative effect)

2) inorganic Hg compounds
HgCl2 - "sublimate" - soluble in water = toxic
- corrosive ulceration of GI tract
- renal failure

Hg2Cl2 "calomel" - low solubility = less toxic


- it was used in medicine ! (diuretic and purgative
effect, ointments in dermatology)
- calomel electrod (reference electrod - measurement of pH)

2) organic Hg compounds
- often extremely toxic
- dimethylmercury

Hg(CH3)2

damage of CNS (central nervous system)


- one of the strongest known neurotoxins !

"The Minamata Disease" - mass Hg poisoning in Japan in 1956


- Minamata Bay waste industrial water with Hg2+
biomethylation by a variety of microorganism
bioaccumulation in FISH
dietary intake from fish diets
Poison grain disaster in Iraq (1971) - seed grain mercury-treated to prevent rot
was used as FOOD

Elements of group III


III A

III B

Borum

Sc

Al

Aluminium

Ga

La

In

Ac

Tl
Ra

Boron

(Borum)

PLANTS micromineral
Boric acid

H3BO3 - a very weak acid


- disinfectant (used in dermatology and ophtalmology)
- also toxic properties !

glutamine synthetase

glutamine

NH3 + glutamate
H3BO3 = inhibitor
toxic to BRAIN

Sodium tetraborate Na2B4O10 = borax

(fusible glaze for pottery)

Aluminium

Al

in human body only traces contamination ?


Al(OH)3 together with MgO or Mg(OH)2

oral antacid

(neutralization of acid in the stomach)

Al also considered as toxic


ACID RAIN

SOIL release of Al3+ !

Elements of group IV
IV A

IV B

Carboneum

Ti

Si

Silicium

Zr

Ge

Hf

Sn

Stannum

Pb

Plumbum

Carbon

(Carboneum)

the most important biogenic element


organic compounds (covalent bonds C-C, chains, rings)
biomolecules: proteins, nucleic acids, lipids, carbohydrates
combustion CO, CO2
respiration CO2
Toxic:

CO

HCN

competes with O2 for hemoglobin

reaction with cytochromes inactivation of cell respiration

Silicon

Si

(Silicium)

abundant element in lithosfere, but not useful in human body


SiO2 (silica)

Quartz - common mineral in the Earths crust

- many varieties: amethyst (purple)


citrine (yellow)
morion (dark-brown)
rose quartz (pink)
- in many rocks (granit, sandstone), metallic ores
cutting, breaking, crushing, ...

inhalation of fine SiO2 dust SILICOSIS - lung disease


occupational disease (miners, ceramics workers)
progressive, signs of it will appear years after exposure !

Silicic acids:

general formula

n SiO2 . m H2O

H4SiO4 orthosilicic acid


Silicates - salts of silicic acids

SiO44-

Si atom - tetrahedral coordination by 4 oxygens

complex structure - different degrees of "polymerization"

linear arrangement FIBERS (asbestos)


planar arrangement MICAS

Silicate minerals - largest class of rock-forming minerals

Medical Chemistry (1st year)

Lecture III
MUDr. Vlastimil Kulda

Elements of group V
VA

VB

Nitrogenium

Phosphorus

Nb

As

Arsenicum

Ta

Sb

Stibium

Bi

Bismuthum

Vanadium

Nitrogen
N2

78% of the atmosphere

- principal bioelement:

(Nitrogenium)
- chemically rather inert

organic compounds ( "NH3 derivatives" )


AMINO ACIDS

PROTEINS

many heterocyclic compounds


pyrimidine

uracil, thymine, cytosine


NUCLEIC ACIDS
(DNA, RNA)

purine

adenine, guanine

NH3

ammonia

- sharp odour
toxic properties for animals

NH4+ ammonium ion

N2O

Nitrous oxide [ Dinitrogen oxide ]


= "laughing gas"
- surgery: inhalation insensibility to PAIN
= anaesthetic and analgetic effects (without muscle relaxation)
obstetrics - pain relief during childbirth

NO
NO2

Nitric oxide [ Nitrogen monoxide ]


Nitrogen dioxide - reddish-brown gas

in the environment
-toxic gases
(Photochemical smog)

Biological functions of NO
= important gaseous signaling molecule !!!
EDRF = endothelium-derived relaxing factor

NO

Endothelial cell

NO

Smooth muscle cell

NO synthesis

diffusion

relaxation

Nitroglycerin vasodilator

NO

- treatment of angina pectoris


(a lack of blood suply of heart muscle chest pain)

Nitroglycerin = glyceryl trinitrate - oily explosive liquid

[ DYNAMITE ]

Biochemical formation of NO
Arginine
(amino acid)
enzyme: NO

synthase

NO

halflife: ~ 4 sec.

Citrulline

Functions of NO: 1) dilation of blood vessels vasodilator ( = EDRF )


2) neurotransmitter
3) in macrophages and neutrophils immune response
(NO is toxic to bacteria)
4) role in penile erection

HNO2

Nitrous acid (INN: Acidum nitrosum)

salts: nitrites

NaNO2

- weak acid, not stable

Sodium nitrite (INN: Natrii nitris)

- toxic !
food additive: alters the color of preserved meat
prevents growth of Clostridium botulinum
(botulinum toxin botulism)
organic nitrites = esters of nitrous acid

Amyl nitrite treatment of angina pectoris

HNO3

Nitric acid

(INN: Acidum nitricum)

- strong acid
- oxidazing agent !

salts:

nitrates

AgNO3

Silver nitrate (INN: Argenti nitras)

Toxicity of NO2- (NO3-)


NO3-

intestinal bacteria can reduce nitrates to nitrites:


Limits for drinking water: NO3-

50 mg/l

1) Methemoglobinemia

HEMOGLOBIN

adults

15 mg/l

NO2infants

"blue baby syndrom"


nitrites

METHEMOGLOBIN
FeIII

FeII

unable to transfer O2
methemoglobin reductase

"protective enzyme" - insufficient in infants !

2) Nitrosamines

Nitrites can react with secondary amines

Nitrosamines

CARCINOGENS !
Nitrites in food - meat and cheese products preserved with
nitrite pickling salt !!!

Phosphorus
-

principal bioelement

H3PO4

Phosphoric acid

(INN: Acidum phosphoricum)

- in biochemistry: "phosphates" = esters of H3PO4

1) Bone and tooth mineral:

hydroxyapatite

Ca5(PO4)3OH

2) Anions in body fluids:

H2PO4- / HPO42-

3) Nucleotides, DNA, RNA


4) Structural lipids (phospholipids) - membranes !

5) Metabolic intermediates (Glucose6phosphate, ...)


6) High energy compounds

ATP

ATP = adenosine triphosphate


ester bond
phosphoanhydride
bonds

ATP + H2O

ADP + Pi + energy

ATP + H2O

AMP + PPi + energy


pyrophosphate

DE = - 30.5 kJ/mol

ATP = adenosine triphosphate


ATP is used to drive many energy consuming reactions !
ATP is used as "energy" for active transport ("pumps")

ATP is often used to "activate metabolites":


hexokinase
ATP
glucose

ADP
glucose-6-P

ATP is formed from ADP when "fuel molecules" are oxidized.

glucose CO2 + H2O

up to 36-38 ATP / molecule of glucose

(majority of this ATP production: oxidative phosphorylation in mitochondria)

Organophosphate neurotoxins
Sarin, soman, tabun - "nerve gases"

Sarin

- extremely toxic substances !!!


- chemical weapons of mass destruction

very potent insecticid

Parathion

also highly toxic !

inhibition of the enzyme acetylcholinesterase !

neuronal synapse

neurotransmitter

receptor

effect

receptor

synaptic cleft
2)

vesicles with
neurotransmitter

1)

Neurotransmitter must be removed from the synaptic cleft (after its job is done) !
1) REUPTAKE
2) Enzymatic breakdown into inactive fragments - ACETYLCHOLINE
(acetylcholinesterase)

Cholinergic synapses

( neurotransmitter = acetylcholine )
botulinum toxin

vesicles with
acetylcholine (ACH)

(release of ACH is blocked)

organophosphates

synaptic cleft

(acetylcholinesterase is blocked)

*
ACH receptor

ATROPINE
(ACH receptor is blocked)

* acetylcholinesterase

*
acetylcholine

choline

acetic acid

Vanadium

- trace element in certain species

vanadium-associated proteins - O2 transport in some primitive classes of animals ?

Ta

Tantalum

- metallic element highly resistent


- biologically inert
- surgical implants

As

Arsenicum

- toxic in all forms

dentistry root canal therapy (devitalisation of tooth) arsenic compounds


SALVARSAN - organic compound containing As
- drug that was used to treat syphilis !
- the first effective "chemotherapeutic agent"
before penicillin (1940s)
- severe side effects

Elements of group VI
VI A

Chalcogens

VI B

Oxygenium

Cr

Chromium

Sulfur

Mo

Molybdaenum

Se

Selenium

Wolframium

Te

Tellurium

Po

Oxygen
O2

(Oxygenium)

21% of the atmosphere

- principal bioelement:

- OH

H2O
many functional groups in biomolecules

"hydroxyl group"

alcohols, phenols

"carbonyl group"

aldehydes, ketones

- COOH

"carboxyl group"

carboxylic acids

electron acceptor in biologically important oxidations !


O2 + 4 e-

2 O2-

+ 4 H+

2 H2O

Oxygen radicals

- TEXTBOOK (Toxicity of oxygen)

very reactive can cause damage to most cell components !!!


O2 + e-

O2-

superoxide radical

+ H+

O2H

perhydroxyl radical
(hydroperoxyl)

H2O2 + e-

OH-

ROS = reactive oxygen species

OH

hydroxyl radical

not only "free radicals", also H2O2

Sulphur

(Sulfur)

- principal bioelement
H2S

- SH

Hydrogen sulphide

- strong poison
- gas with odour of rotten eggs

sulfhydryl groups in organic structures


(often: active groups of proteins enzymes)
protein

SH
SH

Toxic heavy metals ( Pb, Hg, As, ...) - block sulfhydryl groups !

H2SO3

Sulphurous acid (INN: Acidum sulfurosum)

salts: sulphites

H2SO4

Sulphuric acid

( ........ sulfis )

(INN: Acidum sulfuricum)

salts: sulphates

H2S2O3

- weak acid

Thiosulphuric acid

- strong acid

( ........ sulfas )

(INN: Acidum thiosulfuricum)

salts: thiosulphates
( ........ thiosulfas )

H2S

Hydrogen sulphide

salts: sulphides

(INN: Acidum hydrosulfuricum)


( ........ sulfuridum !!! )

Amino acids containing sulphur


cysteine ( Cys )

methionine ( Met )

- essential amino acids

- in proteins

Redox reactions
R

SH

-2H

SH

2H

disulfide bond

-SS-

disulfide bonds stabilize the folded form of a protein


S

intermolecular -S-S- bonds

SH

oxidation

intramolecular -S-S- bond

O
S

OH

"sulfates"

sulfate groups - modification of polysaccharides


(heparine, chondroitin sulfate, keratan sulfate, ...)
-----------------------------------------------------------------------------Vitamins containing S
important

lipoic acid

vitamin B1 (thiamin)

COENZYMES

biotin

Coenzyme A - thiol

pantothenic acid

- acyl group carrier

thiol + carboxylic acid thioester


("high energy bond")

coenzyme A

Acetyl-CoA
important molecule in metabolism

Selenium

Se

trace element
- in enzymes:

glutathion peroxidase (destruction of peroxides)

- chemically related to sulphur analogous amino acids

selenocysteine

= "rare amino acid" in some proteins: thyroid hormone deiodinases

Chromium

Cr

trace element
- component of "glucose tolerance factor"

potentiates the effects of insuline


( better binding to receptors ? )
------------------------------------------------------------------------------------------------

Molybdenum

Mo

(Molybdaenum)

trace element
-cofactor of several enzymes:

xanthine oxidase
xanthine

uric acid

Elements of group VII


VII A

Halogens

VII B

Fluorum

Mn

Cl

Chlorum

Tc

Br

Bromum

Re

I
At

Iodum

Manganum

Fluorine
trace element
Ca5(PO4)3F

(Fluorum)
F2

fluorapatite

yellowish very reactive gas

- bones, teeth

compounds of fluorine ( NaF ) toothpaste to prevent dental caries

excessive consumption of F-

"fluorosis" - damage of dental enamel


(white spots, mottling of enamel)

Freons (chlorofluorocarbons) - destruction of O3 layer


Hydrofluorocarbon derivatives - inhalational general anaesthetics
halothane
(isofluran, sevofluran, ...)

Chlorine
Cl2

Cl

(Chlorum)

pale green poisonous gas, suffocating odour

World War I

chemical weapon destruction of lungs !


(it was soon replaced by more deadly gases phosgene, ...)

COCl2

Cl
Cl2 + H2O
HClO

HCl
HCl

Chlorination of water

HClO

- to KILL bacteria

Cl

Cl-

important anion in body fluids


the main EXTRAcellular anion

(97 108 mmol/l)

Physiologic saline solution (= isotonic = same osmolality as blood plasma)

NaCl

0.9 %

Inorganic acids
HCl

Hydrochloric acid

Acidum hydrochloricum

HClO

Hypochlorous acid

Acidum hypochlorosum

HClO2

Chlorous acid

Acidum chlorosum

HClO3

Chloric acid

Acidum chloricum

HClO4

Hyperchloric acid

Acidum hyperchloricum

HCl - stomach !

CHCl3

Chloroform

- one of the first anesthetics (~ 1850)

- inhaled vapour insensibility "painless surgery"


- hepatotoxic !
phosgene !
- 2 CHCl3 + O2
2 HCl + 2 COCl2
(war gas)

CCl4

Tetrachloromethane ( Carbon tetrachloride)


- solvent
- hepatotoxic ! ( = liver damage )

CH3CH2Cl

Ethyl chloride
- boiling point 13o C
- evaporation cooling down the skin pain relief
- local skin anesthesia (sport injuries , ...)

CH2

CHCl Vinyl chloride

- is used to produce its polymer: PVC

DDT

(dichloro-diphenyl-trichloroethane)

best known banned pesticide


(insecticide)
high solubility in lipids !
contact poison for INSECTS only:
lipids of insect cuticule penetration to nervous ganglia paralysis death
DDT was used with great effect to prevent insect-borne diseases !
(mosquitoes MALARIA
lice spotted TYPHUS)
environmental impact ! - long half life = persistent pollutant
magnifying through the food chain accumulation in fatty tissue
(reproductive toxicity, carcinogen ?, ...)

1960s USA - DDT - major reason for the decline of the bald eagle
(impaired quality of eggshells)

Polychlorinated biphenyls PCBs

biphenyl

good technical properties were used as: insulating materials


cooling fluids in transformers
additives in plastics
PROBLEM: very stable ! = persistent pollutants
contamination of soil

plants

animals

BANNED
cumulation in lipids, milk
(carcinogens ?)

DIOXIN
tetrachlorodibenzo-1,4-dioxin

TCDD
(the most toxic dioxin)

general poison

LD50 = 10 - 100 g/kg

very stable, very resistant (up to 800o C)

("lethal dose")

persistent pollutant

accumulation in fatty tissues - teratogens, mutagens, carcinogens


by-product of production of herbicides
Vietnam War - Agent Orange (herbicide contaminated by TCDD)
1976 Seveso (Italy) - industrial accident uncontrolled reaction
explosion of chemical reactor cloud containing dioxin !

Iodine

(Iodum)

trace element
as element: purple black solid

sublimes into purple gas !

- solubility in water can be increased by addition of KI


Lugols solution

( I2

KI

water )

desinfectant

tincture of iodin = I2 in ethanol

starch + iodine

complexes of deep blue color

starch = mixture of a-amylose linear polymer of glucose


amylopectin branched polymer of glucose
- polysaccharide of PLANTS in FOOD

Thyroid hormones

T4

thyroxine
deiodinases in tissues
Se (selenocysteine) !

T3

triiodothyronine

smaller quantity, greater activity !

Function:

stimulation of metabolism (act to increase the metabolic rate)


essential to proper development (BRAIN !)

Disorders
Deficiency of thyroid hormones

= hypothyroidism
metabolism

low body temperature


intolerance to cold
weight gain
weakness, lethargy

- children: mental retardation, short stature [ CRETENISM ]


Excess of thyroid hormones

= hyperthyroidism ( Graves disease )


metabolism

intolerance to heat
weight loss
increased heart rate
(tachycardia)

GOITER (Latin STRUMA) = enlarged thyroid gland


(function of the gland can be low, normal, high)

Iodine is necessary for the synthesis of the thyroid hormones !!!


FOOD

THYROID
GLAND

BLOOD

I-, IO3-, ...

very effective in
uptake of Ifrom blood !!!

thyroid
peroxidase

2 I-

I2
iodination

THYREOGLOBULIN
TSH (Thyroid-stimulating hormone)

proteolysis

hormone release into the blood

Thyroid gland is composed of spherical "follicles"

uptake of I-

I-

thyreoglobulin

I2

T4, T3 release
into blood

follicular cells

"Colloid" inside the follicles is


rich in protein
THYREOGLOBULIN

Iodine in food
seafood - rich of iodine !
inland areas (Czech republic !!!)

iodine deficiency
endemic goiter
endemic cretenism

prevention: iodised SALT ( = table salt fortified with NaI, KI, or KIO3)
( 25 mg KI / 1 kg of salt )

Radioisotopes of iodine
same properties as "normal" iodine selective accumulation in thyroid gland

Medicine
131

I b

123

I g

- treatment of thyroid cancer or Graves disease


( irradiation causes the destruction of the thyroid tissue )
- imaging and evaluating the function of the gland

131

Chernobyl disaster

129

elevated chances of thyroid cancer


- prevention: taking large amounts of "normal" iodine will saturate thyroid gland

and prevent uptake of "dangerous" radioiodine

Manganese

Mn

(Manganum)

trace element
- cofactor of enzymes:

KMnO4

superoxide dismutase
pyruvate carboxylase

Potassium permanganate

(INN: Kalii permanganas)

- in water dissolves to give deep purple solutions


- strong oxidizing agent
- dilute solutions can act as desinfectant

Elements of group VIII


VIII A

Noble
gases

VIII B

Ferrum

He

Fe

Co

Ni

Cobaltum

Ne

Ru

Rh

Pd

Niccolum

Ir

Pt

Ar

Kr
Xe
Rn

Os

Iron

Fe

(Ferrum)

important microelement
human body: 45 g Fe
a) functional form

- heme iron proteins hemoglobin 70 %


myoglobin
5%
some enzymes
- non-heme iron proteins
b) tranport form (transferrin)
c) storage of iron (ferritin, hemosiderin)
20 %
Fe in food 10-30 mg/day

absorption: only 7-10%

~ 1 mg/day

HEME iron proteins


Hemoglobin

- O2 transport in blood

- in red blood cells


- tetramer = 4 subunits
(each subunit: one heme + one globin)

HbA
HbF

("adult")
("fetal")

a2b2
a2g2

Myoglobin - "O2 storage" in muscle cell


Cytochromes

heme

- electron transport
- their function is based on:

Fe2+ (reduced)

Fe3+ (oxidized)

Non-heme iron proteins

FeII or

FeIII bound to

protein

SH

ironsulphur proteins (FeS proteins)

Transferrin - blood plasma protein ( b1 globulin )


- transport of Fe
- 1 molecule of transferrin can carry 2 iron ions in form of Fe3+

Ferritin - intracellular iron storage protein (liver, bone marrow)


- 1 ferritin complex can store about 4500 Fe3+
- ferritin without iron = apoferritin
Hemosiderin - "damaged (Fe-overloaded) ferritin" - Fe from it is less available

Overview of iron metabolism


FOOD

tissues
CYTOCHROMES
Fe-S proteins

liver
FERRITIN

HEMOSIDERIN

muscles
MYOGLOBIN

blood plasma
TRANSFERRIN

bone marrow
FERRITIN

spleen
FERRITIN

red blood cells


HEMOGLOBIN

BLEEDING (Fe losses)

Iron metabolism = unique


- reutilization !

(closed system)

NO regulated excretion system for Fe !


Fe absorption must be "regulated"
Loss of Fe through loss of blood (females
Iron deficiency - microcytic anemia

Iron overload

- mestrual bleeding)

"iron deficiency anemia"

- hemochromatosis = accumulation of iron in the body


(depositions as hemosiderin)
organ dysfunction (liver, heart, ...)

Iron absorption
FOOD Fe3+
STOMACH
HCl pH 1-2
ascorbic acid
gastroferrin - iron binding protein

reduction

Fe2+
Fe3+
apoferritin

BLOOD

ferritin
(Fe3+)

INTESTINAL MUCOSA CELL

Fe2+

transferrin (Fe3+)

Cobalt

Co

(Cobaltum)

trace element
- central atom of vitamin B12 (cobalamin)
(daily intake ~ 1 g "the liver store": 35 years !)

Vit. B12 deficiency


megaloblastic anemia

pernicious anemia due to impaired absorption !


Absorption of vit. B12
gastric parietal cells

B12
intrinsic factor

complex B12 intrinsic factor


absorption in terminal ileum

Good practices of food chain


in Polish food industry
facts and chalanges

Magorzata Korzeniowska
Wrocaw University of Environmental and Life Sciences

Life Cycle Assessment

Definition of food chain


A food supply chain, logistics network, or supply network is a coordinated system
of entities, activities, information and resources involved in moving a product or
service from supplier to customer.
The entities of a supply chain consist of primary producers,secondury production,
manufacturers, service providers, distributors, and retail outlets. Food supply
chain activities transform raw materials and components into a finished product.
The primary objective of
food
supply
chain
management is to fulfill
customer
demands
through the most efficient
use of resources.

Sustainable food chain


Environmental
objectives:
1) air pollution control,
2) water pollution
control,
3) soil pollution control,
4) noise pollution
control,
5) protection against
radiation.

Nutritional objectives:
1) providing enough food for
mankind,
2) providing nutritious food
(macro- and microelements),
3) providing safe food,
4) providing stable food
delivery,
5) providing food in time and
place required by
consumers.

Economic objectives:
1) achievement of equality
point between supply and
demand,
2) ensuring moderate
food prices,
3) maintenance of job
posts,
4) maximization of added
value,
5) maximization of return
on investment.

Social objectives:
1) ensuring a good standard of life for families of farmers, processors, traders
and all involved in the food chain,
2) promotion of good interpersonal relations between people involved in the food
chain,
3) promotion of good health of all food consumers,
4) promotion of prolonged lifespan of all food consumers.

Relationship betwen food quality , food health quality and food safety traits

Food quality

Safety (hazard-free)
Nutritional values
Sensory values
Convenience

Food
Healthy
Quality

Obligation of food safety and quality systems

Quality & Safety


Assurance and Management
Systems

Obligatory
(required by law)

Safety
GMP/GHP, HACCP

Voluntary
(expected by consumers)

Quality
QACP, ISO 9000, ISO 14000

Diagram of the relationship between GMP, GHP, HACCP, QACP, QMS


(ISO-9000, ISO-14000, etc.) and TQM (Sikora & Strada)

Integration of good nutritional practice in quality system

Good Practice means activity of the quality assurance which ensures that food
products and food related processes are consistent and controlled to assure
quality procedures in food systems.

If analyse good practices we can find three categories of good practices:


Directly connected with food (i.e.: GMP good manufacturing practice)
Indirectly connected with food issues (i.e.: GRP good research practice)

Needed be not existing in reality (i.e.: GKP good housekeeping practice)

Good practices directly conected to food issues


good agricultural practice (GAP)
good catering practice (GCP)

good housekeeping practice (GKP)


good hygiene practice (GHP)
good laboratory practice (GLP)
good manufacturing practice (GMP)
good retail practice (GRP)
good storage practice (GSP)
good transport practice (GTP)

GAP
Good Agricultural Practice is selection of the methods of land use which can best
achieve the objectives of agronomic and environmental sustainability in primary
food production.
A GAP approach aims at applying available knowledge to addressing environmental,
economic and social sustainability dimensions for on-farm production and postproduction processes, resulting in safe and quality food and non-food agricultural
products. Based on generic sustainability principles, it aims at supporting locally
developed optimal practices for a given production system based on a desired
outcome, taking into account market demands and farmers constraints and incentives
to apply practices.

World agriculture in the twenty-first century is faced with three main challenges:
1) to improve food security, rural livelihoods and income;
2) to satisfy the increasing and diversified demands for safe food and other products;
3) to conserve and protect natural resources.

GAP principles:
1. Soil
2. Water
3. Crop and fodder production
4. Crop protection
5. Animal production
6. Animal health and welfare
7. Harvest and on-farm processing and storage
8. Energy and waste management
9. Human welfare, health and safety
10. Wildlife and landscape

GCP
Good catering practice consist of practical advices and assistance to
managers of catering (food service) outlets and suppliers to caterers.
The Guidelines concentrate on the essential steps needed to ensure that the
food served is always safe and Wholesome.

GHP
Good Hygiene Practice refer to procedures that must be undertaken and hygiene
conditions that have to be fulfilled and monitored at all stages of production or
trade in order to guarantee food safety.

Good Hygiene Practice consists of practical procedures and processes that return
the processing environment to its original condition (disinfection or sanitation
programmes); keep building and equipment in efficient operation (maintenance
programme); control of cross-contamination during manufacture (usually related
to people, surfaces, the air and the segregation of raw and processed product).

GLP
Good Laboratory Practice consists of a qualitative system governing organisational
processes and conditions of planning, implementing, controlling, recording and reporting.
The principles which consist of GLP are intended to identify the GLP requirements for test
facilities (laboratories) which perform studies for regulatory purposes.

GMP
Good Manufacturing Practice denotes all the actions that must be undertaken and
conditions to be fulfilled in order to ensure that production of food, wrapping materials and
other materials expected for contact with food, is executed in proper way to guarantee safe
end products and safe food for human consumption.

Good Manufacturing Practice consists of practical procedures and processes that ensure
quality system, provide consistent manufacture and control of products by qualitative
criteria and conformity assessing criteria with intended purpose as required by the
marketing authorisation and specification of the product. It is part of the quality assurance
which ensures that food products are consistently produced and controlled to the quality
standards appropriate to their intended use.

GMP principles:
1. Cleaning and disinfection
2. Pest control
3. Water and air quality
4. Temperature control
5. Personnel (facilities, hygienic way of working, health, education)
6. Structure and infrastructure (surrounding area, building, materials, equipment)

7. Technical maintenance
8. Waste management
9. Control of raw material
10. Work methodology

GRP
Good Retail Practice consists of practical procedures and processes that ensure the right
products are delivered to the right addressee within a satisfactory time period and at
required conditions. A tracing system should enable any faulty product to be found and
there should be an effective recall procedure.

GSP
Good Storage Practice consists of practical procedures and processes that ensure
appropriate handling of foods, regarding implementation and control of product storage in
accordance with a defined regime prior to their use.

GTP
Good Transport Practice consists of practical procedures and processes that ensure a
qualitative system governing the organization, implementation and control of transport of
food products from the producer to the final user.

Good Nutrition Practice interlinking relevantgood practices in food supply chain

Good Nutritional Practice as basis for launching Good Life Practice principles

The Prerequisite Programme (GHP/GMP) is the first step to implementation of


food safety and quality systems along the entire food chain beginning with the initial
production, feed production, animal rearing, processing, transport and ending with
the retail trade. The area covered by the GHP and GMP requirements [Turlejska
2003] comprises:
the site, surroundings and infrastructure of the enterprise,
enterprise facilities and their functional layout,
machines and equipment,
washing and disinfecting processes,
water supplies,
waste control,
pest protection and appropriate control in this field,
personnel training,
personnel hygiene,

keeping documentation and records in the area of GHP.

New European Union Food Hygiene Regulations require that all food businesses (except
primary producers) implement food safety management procedures based on HACCP
principles from 2006. The principal objective of the new general and specific hygiene rules
is to ensure a high level of consumer protection with regard to food safety (Regulation EC,
2004).

HACCP (hazard analysis and critical control point)

is a quality management system for effectively and efficiently ensuring


farm-to-table food safety by controlling microbial, chemical, and physical
hazards associated with food production. A prevention-based system, it
takes a proactive approach by identifying the principal hazards and the
control points where contamination can be prevented, limited, or
eliminated across the whole food production process rather than trying to
identify and control contamination after it has occurred. HACCP principles
are being applied to an increasing range of food products.

Critical control points (CCPs) are the result of hazard analysis and, in practical
conditions, they can be treated as an operation or action that the manufacturer must
pay special attention to because these points pose real hazards to the safety of food
products in the case of deviations from the established parameters. At the same time
CCPs are the point of control for the identified hazard but is not always the point
where the hazard occurs i.e. enters the food chain. The control can be applied before
the hazard occurs or after i.e. cooking.

CCP decision tree

The HACCP system is based on seven principles which, simultaneously, make


up consecutive stages of its implementation:

hazard analysis, in other words, identification and assessment of threats and


possible hazards of their occurrence and determination of control measures and
methods of counteracting these threats,
determination of critical control points (CCP) in order to eliminate or minimise the
occurrence of hazards,
establish critical limits for the critical control points identified,
determination and implementation of a system for the monitoring of critical control
points,
establishment of corrective actions, if a critical control point does not fulfill the
necessary requirements,
establishment of verification procedures in order to confirm if the system is
effective and acts in accordance with the plan,
elaboration and maintenance of the documentation of the HACCP system
concerning stages of its implementation and determination of the method of data
registration and storage as well as archiving of the system documentation.

The basis for the elaboration and implementation of the HACCP system is the Codex
Alimentarius. Other standards are also known, among others, the Danish Standard
or the new ISO 22000 Standard.

The application of HACCP

Stage 1. effective preparation and planning

Stage 2. the application of the 7 HACCP principles


Stage 3. the implementation of the HACCP study output
Stage 4. the ongoing of the HACCP system

HACCP awarness
and understanding of HACCP concept

Identification and training of the HACCP


team

Baseline audit and gap analysis


(evaluate current control measures)

Plan the HACCP study


(inc. the HACCP system structure)

Stage 1.
Preparation and planning

Describe the product and identify the intended use


Construct and validate process flow diagram
Identifiy hazards and control measures
Identify critical control points
Establish critical limits
Identify monitoring procedures

Establish corrective action plan procedure


Validate the HACCP plan

Stage 2.
HACCP studies and HACCP plan development

Determine method of implementation


Agree actions and timetable

Conduct
awarness training

Set up monitoring
systems

Set up facilities
and equipment

Confirm implementation actions complete

Verify implementation
through audit

Stage 3.
Implementing the HACCP plan

Corrective
actions

Defined standards
and regular audit

Ongoing maintenance

Records review and data


analysis (verification)

Problem solving

Corrective and preventative


action

HACCP plan re-validation

Documentation controlled
update

Stage 4.
Maintaining the HACCP plan

Standards from the ISO 9000 family include standards which implement in various
organisations systems of quality management. They were elaborated in such a way
as to allow their application in different enterprises irrespective of branches in which
they operate. It is, therefore, unimportant if a given organisation manufactures a
product or provides services. The ISO 9000 family comprises the following
standards:
ISO 9000, which embraces the basis of the quality management systems and
terminology [ISO 9000:2000],
ISO 9001, which specifies requirements concerning the quality management
system; it is precisely this standard that is implemented in enterprises [ISO 9001:
2000],
ISO 9004, which specifies guidelines for the improvement of the system already
implemented in a company [ISO 9004:2000],
ISO 19011, which contains
recommendations concerning
auditing [ISO 19011:2002].

ISO 9000 standard in accordance with the eight principles:


customer-oriented,

leadership (leaders establish the unity of the aim and operation of the organisation),
involvement of the personnel,
process approach,
system approach to management,
continuous improvement,
decision taking on the basis of facts,
mutually beneficial cooperation with suppliers.
It also simplifies purchase and supplier qualification procedures and, at the same
time, reduces costs associated with these operations. The quality management
system based on the ISO 9000 standard covers the following areas: management of
the organisation, management of resources, process of product realisation as
well as measurements, analyses and improvement.

The International Food Standard (IFS) and the British Retail Consortium (BRC)
standard are based, among others, on the GHP/GMP principles, the HACCP system and the ISO
9001 standard. However, the above standards include requirements which are not found in any of
the earlier discussed norms and comprise:

the obligation to include in the threat analysis of the hazards associated with allergies,

monitoring of work effectiveness,


the need to cover facial hair with appropriate hygiene masks,
checking of the hands hygiene of workers,
the requirement to carry out application tests of products,
documented system of management of stocks of raw materials and products,
complying with the FIFO principle,
elaboration of a system which allows the company to obtain information about GMO,
elaboration of procedures in case of unusual situations,
the requirement to apply metal detectors,
elaboration of the list of places in the production-storage area where glass and other
hazardous material occur,
development of a procedure for the qualification, approval and verification of suppliers,
total ban of smoking on the entire area of the company.

Both the IFS and BRC standard do not allow any freedom and each, even the smallest
requirement, is described precisely. The advantage of this approach is that there are no
problems with the interpretation of requirements and later on with the overinterpretation of
auditors.

The ISO 22000:2005 standard is a completely new standard published in September


2005 with the aim to unify principles of the quality systems used in the food industry. It
is an optional standard because it goes beyond the framework of the GHP/GMP and
HACCP requirements. Its range encompasses [ISO 22000:2005]:
The Prerequisite Programme (PRP), i.e. the GHP/GMP principles and GAP (Good
Agricultural Practice), GVP (Good Veterinarian Practice), GPP (Good Production
Practice), GDP (Good Distribution Practice ), GTP (Good Trading Practice),
the HACCP system,
the identification system (traceability system),
the quality management system ISO 9001:2000.
ISO 22000:2005 integrates both the quality management system
(ISO 9001:2000) and HACCP system. There are also cross
references between ISO 22000, ISO 9004 and terms and definitions
from ISO 9000.
The most effective system of food quality and safety was designed, which
implemented into existing structure of management can give profits both organisation
and other interested party. Furthermore, it may be implemented independently of
other management systems existing into enterprise.

The level of GHP, GMP and HACCP system


implementation in Polish food industry after accession
to the European Union

The level of GHP implementation in Polish food industry

Source: Morkis G., 2007, 2008

The level of GHP implementation in Polish food industry in 2005

Source: Morkis G., 2007, 2008

The level of GMP implementation in Polish food industry

Source: Morkis G., 2007, 2008

The level of GMP implementation in Polish food industry in 2005

Source: Morkis G., 2007, 2008

The level of HACCP system implementation in Polish food industry

Source: Morkis G., 2007, 2008

The level of HACCP system implementation in Polish food industry in


2005 and 2007

Source: Morkis G., 2007, 2008

Dynamic [%] of GHP, GMP and HACCP implementation in Polish food industry
between 2004 and 2007
industry

GHP

GMP

HACCP

Baking

440

521

1058

Pasta

221

209

227

Cereales

189

173

203

Fruit-vegetables

166

168

167

Mineral water and


beverages

155

175

158

Dairy

18

15

93

Fish

86

Sugar

26

26

40

Teas and coffees

45

53

Oils and fats

Source: Morkis G., 2008

67

Benefits from the implementation of HACCP system


in terms of improving food safety

Trafiaek i Koozyn-Krajewska, 2007

Intangible benefits from the implementation of HACCP system


in terms of improving food safety

Trafiaek i Koozyn-Krajewska, 2007

Tangible and economical benefits from the implementation of HACCP system


in terms of improving food safety

Trafiaek i Koozyn-Krajewska, 2007

Main barriers during HACCP implementation


training,

human resources,
planning,
knowledge and competence,

documentation,
resources,
management commitment

Barriers faced by firms in implementing HACCP

Implementation of HACCP impeded by internal budgetary constraints


Problems obtaining external funding
Current food safety controls considered sufficient
Lot of changes to our production processes needed before HACCP could be put in place
The things needing to be done in order to implement HACCP overwhelmed us
Other investments considered more important
Lot of changes to our food safety controls needed before HACCP could be put in place
Wide scale upgrading of the plant needed before HACCP could be put in place
Scale of operation is too small to have HACCP
Not sure whether the implementation of HACCP would meet future regulatory
requirements
Uncertain about the potential benefits of implementing HACCP
HACCP difficult to implement because of internal organization of the company
Concerned that HACCP would reduce our flexibility in production
Thought it best to wait and see the experiences of other companies before implementing
ourselves
Did not really see HACCP as suitable for our plant
Not sure whether the implementation of HACCP would meet our customers requirements
Considered that costs of implementing HACCP likely to get cheaper over time
Greater priority given to other issues than enhancing our food safety controls
Food safety issues not considered sufficiently important to warrant the investment
HACCP goes against all of the ways in which we have traditionally done things

Factor loadings of barriers to HACCP Implementation:


Uncertainty about potential benefits from HACCP
Perception that current food safety control are sufficient
Tendency to learn from other's experience before acting
Uncertainty about whether future regulatory requirements met by HACCP
Perception that firm's scale of operation is too small for HACCP
Perception that HACCP is not suitable for the firm
Perception that HACCP would reduce the flexibility of operations
Perception that HACCP goes against our traditional methods
Uncertainty about meeting customer requirements with HACCP
Scale and scope of changes prior to adopting HACCP
Scale and scope of changes to food safety controls
Wide scale facility upgrading required for HACCP implementation
Overwhelmed by things to be done to adopt HACCP
Greater priority given to other issues
Food safety investment being a low priority
Relative importance of other investments
Internal budgetary constraints
Difficulty in obtaining external funding

Economic difficulties during the implementation of the HACCP system before


and after Polands accession to the EU

Trafiaek i Koozyn-Krajewska, 2007

Difficulties with personel composition and with essential facts concerning the
problem during the implementation of the HACCP system before and after
Polands accession to the EU

Trafiaek i Koozyn-Krajewska, 2007

What can be done more???


No let-up on the basics
In the food processing environment, constant reinforcement on the food
safety basics is necessary. These basics include such procedures as
personnel hygiene practices and training programs, cleaning, sanitation
and maintenance procedures, effective product recall programs, provisions
for safe water supply, and procedures for handling product throughout the
entire manufacturing and distribution processes.

Continuing consumer education


Once food leaves the processor, there is also a role for consumers and others to
play in maintaining basic food safety precautions. Improper food handling in the
home and at retail food establishments accounts for more reported cases of
foodborne illness than does failure at the food processing level.

Greater use of risk-based criteria and greater flexibility in directing


regulatory resources quickly and efficiently to high-risk areas

Massive restructuring of the nations food regulatory agencies may not be


politically or economically feasible, at least in the short term. However,
attention can and should be focused on strengthening regulatory agency
capabilities in areas where greatest risks lie. In todays world of heightened
terrorist awareness, where deliberate contamination of food supplies is a
very real threat, additional attention and resources will be directed at this
problem. But that effort can complement existing food safety approaches in
many ways. Many of the systems and tools that will strengthen protections
against accidental contamination will also help protect against deliberate
contamination of the food supply.

Expanded partnerships.
The publics perception is that the government will protect them 100 percent
when it comes to eating their food. The reality is that government has to
work in partnership with industry and in partnership with consumers
themselves in guaranteeing safer food.

More sharing of information and less duplication of effort


The advent of international food safety management system standards is
opening up new avenues for cooperation and sharing of data among food
safety regulatory agencies, the food industry, and the network of privatesector organizations that are springing up to audit the food industry to these
new standards. Multiple audits and inspections of individual facilities can be
reduced. These opportunities need to be exploited.

Greater use of economic incentives


Economic incentives are demonstrably more effective than regulatory
pressure. An example is the USDA Agricultural Marketing Services use of
economic incentives and performance standards linked to statistical process
control and continuous improvement to ensure that ground beef purchased
for school lunch programs is safe and meets purchasing requirements. In
the four years that this program has been in effect there has been a
continual improvement in the microbiological quality of the ground beef. If
purveyors want to sell ground beef to the school lunch program, they must
have systems that are shown to be in process control. If a suppliers process
deteriorates, that supplier will be removed from approved status and placed
on conditional status. During this time the supplier must take appropriate
corrective and preventive actions to bring the process back into compliance
with specification. If the supplier fails to do so it will be placed on ineligible
status.

Expanded diligence
performance

by

food

companies

on

supplier

quality

The recent sickening of pets from toxic ingredients blended into pet foods
was more a failure of corporate supplier quality programs than a failure of the
regulatory establishment

Globally applicable tools for a global food chain


Sourcing of food and food ingredients is now a global business, so it makes sense to
tackle food safety issues with internationally accepted and globally applicable tools
such as the ISO 22000:2005 standard.

More effective inspectionnot more inspection


State inspection resources are limited and workload is growing, so these resources
need to be targeted where they are needed most. Food producers and processors
domestic or foreignthat do not show evidence of compliance with HACCP and/or
ISO 22000:2005 and those dealing in higher-risk foodstuff should be subject to closer
surveillance.

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