Transcript Biosynthesis of porphyrins

Conversion of amino acids to specialized
a.a are precursors of many N-containing compounds and are building blocks of proteins.
Pophyrins
Porphyrins: are cyclic compounds that bind metal ions usually Fe+2,Fe+3.
-Metaloporphyrin in human is heme which is prosthetic group for hemoglobin, myoglobin,
cytochromes, catalase and tryptophan pyrrolase
-Heme: one ferrus ion coordinated in the center of porphyrins.
-Heme is highly turned over: 6 – 7 gm is synthesized and destroyed daily
Structure of porphorins
-Ring structure of 4 pyrrole rings linked with methylenyl bridge.
-Side chains: different porphyrins vary of the side chain that are attached to pyrrole
rings.
*Distribution of side chains: different types I, II, III, IV of porphyrins.
Biosynthesis of porphyrins
- The major site of heme is liver
- The biosynthesis occurs in cycle which the
first reaction and the last three reactions
occur in mitochondria, other reactions occur
at cytosol.
-Formation of δ-amino levulinic acid (ALA)
All carbons and nitrogens of porphyrin are
provided by glycine + succinyl CoA. The
reaction is catalyzed by ALA synthase and it
is rate limiting step in the biosynthesis of
porphyrins
-This enzyme is inhibited by Hemin.
-Formation of porphobilinogen
Two molecules of ALA condense to form it by
enzyme amino levulinic acid dehydrase.
Biosynthesis of porphyrins
-Formation of uroporphyrinogen
Condensation of 4 molecules of
porphobilinogen  uroporphyrin III
Formation of heme
Uroporphyrin III is converted to heme by a
series of decarboxylation processes
Biosynthesis of Porphyrins
Degradation of heme
- Life time of RBC is 120 day, RBC are taken up by liver
and spleen and macrophages, and degraded by reticuloendothelial system (RE)
Formation of billirubin
-The first step in the degradation is catalyzed by
microsomal heme oxygenase enzyme of the ER cells.
-The enzyme add the –OH to the methylen bridge
oxidation CO and Fe+3 is released and the product
is Billiverdin and it is reduced into Billirubin.
Uptake of Billirubin by liver
- Billirubin is slightly soluble in water transported in
the blood through complexion to albumin, then taken by
hepatocytes.
Formation of Billirubin diglucuronide
- In hepatocytes, the solubility of Billirubin is increased
by addition of two molecules of Glucuronic acid
catalyzed by “Billirubin glucuronyl transferase” using
UDP-glucuronic acid.
Heme Degradation
Excretion of Billirubin into bile
- Billirubin diglucuronide is transported actively into bile.
Formation of urobillins in the intestine
-Billirubin diglucuronide is hydrolyzed and reduced by bacteria in the gut to yield
urobillinogen.
Urobillinogen
Reabsorbed, go to kidneys and converted to
urobillin (yellow color)
Most are oxidized by bacteria to stercobillin
(brown color)
Jaundice
Yellow color of skin and sclera resulted from high level of billirubin.
high level Billirubin is toxic to CNS
Hemolytic jaundice: sickle cell anemia, or malaria.
Obstructive jaundice: bile duct obstruction.
Hepatocellular Jaundice: liver damage, cirrhosis, hepatitis.
Jaundice in newborns
- Decrease in the activity of Billirubin glucuronyl transferase
Jaundice
Creatine
- Creatine phosphate, high energy compound, formed in the
muscle, can reversibly donate a phosphate group to ADP.
Creatin-P + ADP
creatine kinase
ATP + creatine
This reaction is important to maintain intracellular level of ATP
during the first few minutes of intense muscular contraction.
-The presence of creatin kinase in the plasma diagnosis of
myocardial infarction.
Synthesis of creatine
Creatine is synthesized from glycine + guanidino group of
arginine plus methyl group of activated methionine.
Degradation of creatine
- Creatine and phosphocreatine spontaneously cyclize at slow
but constant rate to form creatinine which excreted into urine.
- The amount of creatinine which excreted to urine is
proportional to creatine level in plasma.
- Creatinine is used to estimate the total body mass.
- Also creatinine level in the urine is indicator for kidney
function.
The End
Synthesis of Histamine
- Histamine is chemical
messenger that mediates a wide
range of cellular responses
including allergy, inflammation,
Gastric acid secretion and
neurotransmission in the brain.
-Histamine resulted from
decarboxylation of histidin.
- It is secreted from mast cells
as resulted of trauma, allergic
reaction.
*Antihistamines
Serotonin
-Serotonin is synthesized from
tryptophan.
- It can be synthesized and
stored in different sites of body.
(small intestine, platelet, CNS)
- It has multiple physiological
roles:
pain., blood pressure,
temperature, sleep, …
Catecholamines
- Dopamin, epinephrine, nor-epinephrine are biologically active amines are collectively
called catecholamines.
- Dopamin and nor-epinephrine function as neurotransmitters in the brain and CNS.
- Nor-epinephrine and epinephrine are synthesized also in adrenal medulla.
Functions
- Out side of nervous system: epinephrine and nor-epinephrine act as regulator of CHO,
lipid metabolism, also regulate blood pressure.
- These amines are released in response to fright, exercise, cold, low level of glucose.
- Increase epinephrineincrease degradation of glucose, TG, increase output of heart
“ Fight or Flight reactions”
Synthesis of catecholamines
- Tyrosine by tyrosine hydroxylase  3,4-dihydroxy phenylamin DOPA (the rate
limiting step in the biosynthesis)
Degradation of Catecholamines
- Catecholamines are inactivated by
oxidative deamination catalyzed by
monoamin oxidase (MAO) and by Omethylation catalyzed by catechol-O-
methyl transferase (COMT).
Melanin
- Melanin is a pigment occurs in number
of tissues (eye, hair, skin)
- In the skin, the pigment forming cells
are called melanocytes.
- Protect the cells from harmful
effects of sunlight
Tyrosine  T.H
Melanin
 Dopa
