Conversion of Amino Acids to Specialized Products PDF

Conversion of Amino Acids to Specialized Products College of pharmacy Stage Three Second semester Lecturer: Dr.Rithab Ibrahim Certain proteins contain amino acids that have been post translationally modified to permit them to perform specific functions. One...

Conversion of Amino Acids to Specialized Products College of pharmacy Stage Three Second semester Lecturer: Dr.Rithab Ibrahim Certain proteins contain amino acids that have been post translationally modified to permit them to perform specific functions. One example is the hydroxylation of lysine to 5-hydroxylysine, whose subsequent modification and cross-linking stabilizes maturing collagen fibers. In addition to serving as the building blocks for protein synthesis, amino acids serve as precursors of diverse biologic materials. Some important biological molecules derived from amino acids 1. Creatine and Creatinine 2. Catecholamines 3. Serotonin and Melatonin 4. Histamine 5. Glutathione (GSH): 6. Formation of purine and pyrimidine rings Creatine and Creatinine Glycine, arginine, and methionine all participate in creatine biosynthesis Creatine is stored in the muscle in the form of creatine phosphate, which acts as energy store. Creatinine is formed in muscle from creatine phosphate by irreversible, nonenzymatic dehydration, and loss of phosphate (used for muscle contraction). The amount of creatinine produced is constant from day to day and depend on muscle mass. Creatinine is excreted in urine. Catecholamines The name catechol refers to the dihydroxylated phenyl ring. The amine derivatives of catechol are called catecholamines  Tyrosine is the precursor for the synthesis of catecholamines, namely dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline). The conversion of tyrosine to catecholamines occurs in adrenal medulla and central nervous system involving the following reactions: Tyrosine is hydroxylated to 3,4-dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. This enzyme catalyses the rate limiting reaction and requires tetrahydrobiopterin as coenzyme.  DOPA undergoes PLP-dependent decarboxylation, catalyzed by aromatic amino acid decarboxylase, to give dopamine. In turn, dopamine is hydroxylated by dopamine β-hydroxylase to produce norepinephrine. Methylation of norepinephrine by S-adenosylmethionine, catalyzed by phenylethanolamine N-methytransferase gives epinephrine.  Norepinephrine and epinephrine regulate carbohydrate and lipid metabolisms. They stimulate the degradation of triacylglycerol and glycogen. They cause an increase in the blood pressure. Dopamine and norepinephrine serve as neurotransmitters in the brain and autonomous nervous system. Serotonin and Melatonin Serotonin or 5-hydroxytryptamine (5HT) is a neurotransmitter, synthesized from tryptophan. Tryptophan is first hydroxylated at 5th carbon by tryptophan hydroxylase. This enzyme requires tetrahydrobiopterin as a coenzyme. 5-Hydroxytryptophan is decarboxylated by aromatic amino acid decarboxylase (PLP dependent) to give serotonin.  Melatonin or N-acetyl 5-methoxyserotonin is a hormone, mostly synthesized by the pineal gland. Serotonin (produced from tryptophan) is acted upon by serotonin N-acetylase (the rate limiting enzyme), to give N-acetylserotonin. The latter undergoes O- methylation, S-adenosylmethionine being the methyl group donor to produce N-acetyl,5-methoxyserotonin (melatonin). The synthesis and secretion of melatonin from pineal gland is controlled by light Histamine A biogenic amine that functions in allergic reactions and gastric acid secretion, histamine is present in all tissues. Histamine is formed by decarboxylation of histidine; the reaction is catalyzed by the pyridoxal phosphate-dependent enzyme histidine decarboxylas Glutathione (GSH): Glutatione is γ-Glutamyl cysteinyl glycine. γ-glutamate is attached via the γ-carbon instead of the α-carbon. The active part is the -SH group of cysteine (sulfhydryl group). Biosynthetic reactions of GSH are catalyzed by γ-glutamyl cysteine synthetase and GSH synthetase