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AND
STEROIDS
Sterols (steroids) are class of
lipids that are derivatives of a
tetracyclic hydrocarbon
Steroids
Steroids are lipids containing a steroid nucleus
(core structure)
The steroid nucleus is a fused ring system
consisting of three cyclohexane rings and one
cyclopentane ring
The rings are designated A, B, C and D
Attachment of different groups to the core steroid
structure leads to a wide variety of steroid
compounds, including cholesterol, bile salts and
steroid hormones
C D
A B
CHOLESTEROL
Cholesterol is the most highly decorated small molecule in
biology. Thirteen Nobel Prizes have been awarded to scientists
who devoted major parts of their careers to cholesterol. Ever since
it was isolated from gallstones in 1784, cholesterol has exerted an
almost hypnotic fascination for scientists from the most diverse
areas of science and medicine. Cholesterol is a Janus-faced
molecule. The very property that makes it useful in cell
membranes, namely its absolute insolubility in water, also makes
it lethal.
6
Cholesterol
Cholesterol is the most abundant steroid in animals
- plants have very small amounts (but have related
compounds)
- its a major component of cell membranes, and
affects the fluidity of the membrane due to its bulky
structure
- is a precursor for biosynthesis of many other
steroids
Cholesterol is called a sterol because it contains an
alcohol group
We can obtain cholesterol from our diet (animal
products), but our liver can also synthesize all the
cholesterol that we need
- the liver synthesizes more cholesterol when dietary
intake is low
- excessive blood cholesterol is associated with
atherosclerosis and formation of gallstones
HO
History
1855 Addisons disease
1856 Adrenal glands essential for life
1930 Cortex > medulla
1932 Cushings syndrome
1949 Hench et al (Steroids in rheumatoid
arthritis)
1952 Aldosterone
CHOLESTEROL IS THE BIOSYNTHETIC
SOURCE OF ALL STEROIDS
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Steroid Hormones
Hormones act
as chemical
messengers
They are
important in
control of many
biological
functions
They are
secreted from
endocrine glands
(and placenta)
They react with
receptors on cell
surfaces to
trigger a cascade
response
Usually control
metabolism at
Adrenal Corticosteroids
Adrenal corticosteroids are hormones produced in
the adrenal glands (located just above the kidneys)
Cortisone (a glucocorticoid) raises the blood glucose
level by causing tissues other than the brain to switch
to metabolizing fats and proteins; it also suppresses
the immune response and can be used as an anti-
inflammatory anti-allergy medication
Aldosterone (a mineralcorticoid) regulates ion
balance by promoting re-absorbtion of Na+, Cl- and
HCO3- by the kidneys
Prednisone is a synthetic corticoid used to treat
various inflammatory conditions, such as asthma and
rheumatoid arthritis
CHOLESTEROL IS THE BIOSYNTHETIC
SOURCE OF ALL STEROID HORMONES
Five major classes of hormones
Progestins (regulate events during
pregnancy and are precursors to all
other steroid hormones)
Androgens (male sexual characteristic
development and maintenance)
Estrogens (female sexual characteristics
development and maintenance)
Glucocorticoids (promote
gluconeogenesis, and in certain doses
suppress inflammation rxns)
Mineralocorticoids (regulate ion balance
Actions 1
Direct (Intended) Actions
Anti-inflammatory
Anti-allergy
Anti-immunity
Permissive Actions
Lipolytic effects
Effect on BP
Effect on bronchial muscles
Actions 2
Glucocorticoids (e.g., prednisolone) used
to suppress inflammation, allergy and
immune responses.
Anti-inflammatory therapy is used in
many illnesses (e.g., Rheumatoid
Arthritis, Ulcerative Colitis, Bronchial
Asthma, eye and skin inflammations).
-Useful in, say, tissue transplantation and
lymphopoiesis (leukemias and
lymphomas).
Striking improvements can be obtained,
Glucocorticoids (e.g., prednisolone) used to suppress
inflammation, allergy and immune responses.
Anti-inflammatory therapy is used in many illnesses
(e.g., Rheumatoid Arthritis, Ulcerative Colitis,
Bronchial Asthma, eye and skin inflammations).
Actions .. 3
Hydrocortisone used for: orally for
replacement therapy, i.v. for shock
and asthma, topically for eczema
(ointment) and enemas (ulcerative
colitis).
Triamcinolone: used for severe
asthma and for local joint
inflammation (intra-articular inj.).
Triamcinolone: used for severe asthma and
for local joint inflammation (intra-articular
inj.).
Actions .. 4
Betamethasone and dexamethasone:
very potent, w/o salt-retaining
properties; thus, very useful for high-
dose therapies (e.g., cerebral
edemas).
Beclometasone, diproprionate,
budesonide: pass membranes poorly;
more active when applied topically
(severe eczema for local anti-
inflammatory effects) than orally;
used in asthma, (aerosol).
Beclometasone, diproprionate, budesonide: used in asthma,
(aerosol).
BILE ACIDS ARE CHOLESTEROL
DERIVATIVES
Emulsify dietary lipids
Secreted from liver, stored in gall bladder,
passed through bile duct into intestine
Bile acids represent a major metabolic fate
of cholesterol, accounting for more than
half of the 800 mg/day of cholesterol
metabolized (steroid hormones represent
about 50 mg of cholesterol per day)
Bile acids are recycled through small
intestine
Bile Salts
Bile salts are synthesized from cholesterol
in the liver
- they are stored in the gall bladder and
released into the upper small intestine to
help break down fats and oils (like soaps)
- too much accumulated cholesterol in the
gall bladder can lead to gallstones; if a
gallstone passes into the bile duct, severe
cholic acid, a bile acid
pain results and the gallbladderO often has
to be removed CH3
C CH2
OH N - +
COO Na
CH3
H
glycine, an amino acid
CH3
HO OH
sodium glycocholate, a bile salt
Bile acids
H
N CH2 CH2 SO3H
Tauro ~
Gliko ~ H
N CH2 COOH
COOH
HO
Cholesterol
Tauro ~
Glyco ~ HO OH
H COOH
HO Chenodeoxycholic acid
COOH
HO
H
Litocholic acid
HO OH
H Cholic acid HO
COOH
Secondary
24 bile acids
OTHER ISOPRENOID
COMPOUNDS:
Vitamin A, D, K, E
Terpenes generic term for all
compounds biosynthesized from
isoprene precursors; hence all the
molecules we have discussed today
are terpenes.
OH
H3 C H3 C O
H
H3 C H H3 C H
H H H H
O HO
Testosterone Androsterone
Negative Health Effects
Acne
Irritability and aggression (ROID RAGE)
Elevated cholesterol levels
Adolescent use may cause a premature
stop in lengthening bones (Stunted
growth)
Mood swings (extremes)
Negative Effects, cont.
Injecting users subject themselves to
Hepatitis or HIV.
Withdrawal symptoms when one stops
using steroids: mood swings, fatigue,
restlessness, loss of appetite, insomnia,
reduced sex drive, and depression.
Depression can lead to suicide.
If untreated, the withdrawal symptoms
could last up to a year after stopping the
use.
Bell Ringer
Answer the following question.
Why would someone want to take
steroids? Are athletes the only
users? Why or why not.
Who Uses Steroids?
Athletes in sports that rely on size and
strength: football, baseball, and wrestling.
Endurance athletes: track and swimming.
Weight training or body building athletes.
Thank you