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 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. 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 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 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 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