Metabolism of Amino Acids

• The metabolism of amino acids involves biosynthesis, catabolism, conversion to specialized products, and the conversion of amino acids to essential amino acids.
• Nonessential amino acids are synthesized from intermediates of metabolism and essential amino acids.
• Amino acids such as Alanine, Aspartate, and Glutamate are synthesized by transfer of an amino group to the α-keto acids.
• Glutamine, Asparagine, Proline, Serine, and Glycine are synthesized by amidation.
• Serine arises from 3-phosphoglycerate and can also be formed from glycine through transfer of a hydroxymethyl group.
• Glycine is synthesized from serine by removal of a hydroxymethyl group.
• Tyrosine is formed from phenylalanine by phenylalanine hydroxylase.
• NH3 + O2 → CCH2CH2CH2CHCO2 - NH3 + O2 → CCH2CH2CH2CH2 Glutamate Gamma - aminobutyrate (GABA) Glutamate decarboxylase CO2
• Glutamate is the precursor of the glutathion and GABA.
• Histamine is a chemical messenger that mediates a wide range of cellular responses, including allergic reactions, inflammatory reactions, gastric acid secretion, and possibly neurotransmission in parts of the brain.
• NO also acts as a neurotransmitter, prevents platelet aggregation, and plays an essential role in macrophage function.
• Histamine is secreted by mast cells as a result of allergic reactions or trauma.
• Histidine is the precursor of the histamine, carnosine, ergothioneine, anserine, and homocarnosine.
• Cysteine is synthesized from homocysteine by condensing with serine, forming cystathionine, which is hydrolyzed to α-ketobutyrate and cysteine.
• This vitamin B6-requiring sequence has the net effect of converting serine to cysteine, and homocysteine to α-ketobutyrate, which is oxidatively decarboxylated to form propionyl CoA.
• Glucogenic amino acids can give rise to the net formation of glucose or glycogen in the liver and glycogen in the muscle.
• The catabolism of amino acids found in proteins involves the removal of alpha amino groups, followed by the breakdown of the resulting carbon skeletons.
• Important products derived from amino acids include Heme, Purines, Pyrimidines, Hormones, Neurotransmitters and Biologically active peptides.
• Amino acids whose catabolism yields either Acetyl CoA or Acetoacetyl CoA are termed ketogenic.
• The major sites of heme biosynthesis are the liver and the erythrocyte-producing cells of the bone marrow.
• Amino acids whose catabolism yields Pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic or glycogenic.
• The initial reaction and the last three steps in the formation of porphyrins occur in mitochondria, whereas the intermediate steps of the biosynthetic pathway occur in the cytosol.
• Creatine is reversibly phosphorylated to creatine phosphate by creatine kinase, using ATP as the phosphate donor.
• Creatine is synthesized from glycine and the guanidino group of arginine, plus a methyl group from SAM.
• The carbon skeletons of amino acids are converted to Pyruvate, Acetyl-CoA, Acetoacetyl-CoA, Oxaloacetate, Alpha-ketoglutarate, Fumarate, Succinyl-CoA.
• These products directly enter the pathways of intermediary metabolism, resulting either in the synthesis of Glucose or lipids, or in the production of energy through their oxidation to CO2 and H2O by the citric acid cycle.
• Glycine is the precursor of the Heme, Purines, Creatine, Glutathione, Bile salts, Serine, Oxalate, Proteins.
• Creatine phosphate is a high-energy compound that provides a small but rapidly mobilized reserve of high-energy phosphates that can be reversibly transferred to ADP to maintain the intracellular level of ATP during the first few minutes of intense muscular contraction.
• Serotonin (5-hydroxytryptamine (5HT)) is synthesized from tryptophan.
• Dopamine and norepinephrine are synthesized in the brain and function as neurotransmitters.
• Nicotinic acid (Niacin) is synthesized from tryptophan through several steps, including the conversion of tryptophan to nicotinamide adenine dinucleotide (NAD).
• Arginine is the precursor of the Nitric oxide (NO) and Polyamines, including Putresine, Spermine, Spermidine, Ornitine, and Urea.
• The largest amount of serotonin is found in cells of the intestinal mucosa, with smaller amounts occurring in the central nervous system, where it functions as a neurotransmitter, and in platelets.
• Synthesis of NO, catalyzed by NO synthase, involves the NADPH dependent reaction of L-arginine with O2 to yield L-citrulline and NO.
• NO is the endothelium-derived relaxing factor, which causes vasodilation by relaxing vascular smooth muscle.
• The catecholamines are inactivated by oxidative deamination catalyzed by monoamine oxidase (MAO), and by O-methylation carried out by catechol-O-methyl transferase (COMT).
• Melanin is a highly colored polymeric intermediates formed in skin (melanocytes), eyes, and hair.
• The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid, metanephrine and normetanephrine.
• Tyrosine is the precursor of Thyroxine, Epinephrine, Norepinephrine, Dopamine, Melanin, and Tryptophan.
• Norepinephrine is also synthesized in the adrenal medulla, as is epinephrine.