Conversion of amino acids to specialized a.a are precursors of many N-containing compounds and are building blocks of proteins.PophyrinsPorphyrins: 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 dailyStructure 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 reticulo-endothelial 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 solublity 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.

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

Urobillinogen

Reabsorbed, go to kidneys and converted to urobillin (yellow color)

Most are oxidized by bacteria to stercobillin (brown color)

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 glycin + 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.

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 epinephrineincrease 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 O-methylation

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 Dopa

Melanin

The End