Tetrapyrroles

stav biochemie a experimentln onkologie

Tetrapyrroles are a class of chemical compounds whose

molecules contain four pyrrole rings.

Hemoglobin, myoglobin, cytochromes

synthesis

Pyrol
http://en.wikipedia.org/wiki/Pyrrole#/m
edia/File:Pyrrole-2D-numbered.svg

porphyrias

degradation

jaundice

Hem Synthesis I

mitochondrion
cytoplasm

Heme Synthesis II
Hydroxymetylbilan
Hydroxymetylbilan
synthase
- 4 NH3

Uroporphyrinogen III
synthase

Spontaneous non
enzymatic reaction

Glycine

Heme Synthesis III

ALA
syntase

Aminolevulate (ALA)

Porphobilinogen (PBG)

Succinyl-CoA

porfyriny

A ->M

porfyriny

O2

2 P dekarboxylace a oxidace

!
!
Heme

! Mitochondrial enzymes

Heme Synthesis IV

Coproporphyrinogen III

colorless

light
-6H

Coproporphyrin III

color

Signs of accumulation of
purphyrins in tissues

ROS

Demage of cell
membranes

Excitation

Lysosomal enzymes

Demage of tissues

Photosensitivity

Major signs of porphyrias

Anemia

Abdominal pain

Neuropsychiatric
disorder
Photosensitivity

Major signs of porphyrias

ALA
synthase II

ALA
synthase II

Erytroid precursors

lack of heme

anemia

Major signs of porphyrias

abdominal pain

accumulation
of ALA a PB

Neuropsychiatric
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signs

accumulation
of ALA a PB

Photosensitivity

Accumulation of
-rins

Regulation of Heme Synthesis

Glycine

ALA Dehydratase

ALA Synthase I
Aminolevulate (ALA)

Succinyl-CoA

Pyridoxal
phosphate

Pb

How to suppress
signs of porphyrias?
What can aggravate
signs of porphyrias?

Drug interaction
Cytochrome P450
http://medicine.iupui.e
du/Default.aspx

Heme

Porphobilinogen (PBG)

Heme degradation I
Heme

Hemin

hemoxygenase

Bilirubin

Heme
Biliverdin reductase

Biliverdin

Heme

Biliverdin

Bilirubin

Heme degradationII
circulatory system

liver
bilirubin
non conjug.
conjug.
bilirubin

kidney

Ligandiny
Protein Y

Rate limit
conjug.
bilirubin

Ductus choledochus

Non conjug.
bilirubin

Non conjug.
bilirubin

10%
Urobilinogen

Glucuronic
acid

intestine

Urobilinogen

90%

10%
Urobilinogen

Urobilinogen

80%
Urobilins

urine

Urinary tract

Urobilin

feaces

Jaundice

Icterus

Jaundice = sign

Pre - hepatic
hepatic
Post - hepatic

Icterus
Pre - hepatic

bilirubin
Non conjug.

hepatic

Post - hepatic
intestine

liver

conjug.
bilirubin
conjug.
bilirubin

kidneys

Ductus choledochus

bilirubin
Non conjug.

bilirubin
Non conjug.

Urobilinogen

Urobilinogen

Urobilinogen

Urobilin
Urobilinogen

Urinary tract

Hyperbilirubinemia
> 17 mol/l
> 1mg/dL

Pre-hepatic cause of icterus

Pre - hepatic

liver

bilirubin
Non conjug.

intestine
bilirubin
conjug.

kidneys

bilirubin
Non conjug.

Ductus choledochus

Urobilinogen

Urobilinogen

blod
Urobilinogen

urine

Urobilinogen

bilirubin
Non conjug.

Urobilinogen

feaces

total. bilirub.
conjug-bilirubin

Urinary tract

bilirubin
conjug.

Urobilin

< 20% total. bil.

dark

Hepatic cause of icterus

hepatic

Non conjug.
bilirubin

intestine

Demage of liver
conjug.
bilirubin

kidneys

Ductus choledochus

Non conjug.
bilirubin

Urobilinogen

blood
Urobilinogen

Urobilinogen

urine

Urobilinogen

Urobilin
bilirub.

Urobilinogen

Non conjug.
bilirubin

stool

total. bilirubin
Conjug. bilirubin 20-50% total

Urinary tract

conjug.
bilirubin

pale

Post-hepatic cause of icterus

Post - hepatic

liver

Non conjug.
bilirubin

intestine
konjug.
bilirub

kidneys

Ductus choledochus

Non conjug.
bilirubin

blood

urine

feaces

total. bilirub.
conjug.bilirubin
Urinary tract

Urobilinogen

> 50% total. bil.

white

Gilbert-Meulengracht syndrome

- AR hereditary disease
- hyperbilirubinemia
- lower activity of glucuronyl transferase
- higher inncidence in men population
- higher concentration of non-conjugated bilirubin in serum (do cca
80 mol/l)

Newborn jaundice

increased haemolysis+ nezral jtra

- phototherapy
- Concentration of Non-conjugated bilirubin in plasma > 20-25mg/dL
traspases hematoencefalic barier kernicterus
-

Konec
https://www.youtube.com/watch?v=JkrOpmfzACk
https://www.youtube.com/watch?v=bU2srODhfCM