Protein Metabolism Revision PDF

Catabolism of the amino acid nitrogen 1. The nitrogen of the amino group is excreted as ammonia in fish, uric acid in birds and urea in humans. 2. Transamination is catalyzed by aminotransferases which need pyridoxal phosphate (PLP) as a coenzyme. They are reversible reactions. 3. Functions...

Catabolism of the amino acid nitrogen 1. The nitrogen of the amino group is excreted as ammonia in fish, uric acid in birds and urea in humans. 2. Transamination is catalyzed by aminotransferases which need pyridoxal phosphate (PLP) as a coenzyme. They are reversible reactions. 3. Functions of transamination: − Transfer of amino group to α- ketoglutrate to from glutamate which undergoes deamination at sufficient rate to give ammonia − Formation of non- essential amino acids. 4. Clinical importance of ALT and AST: - These are normal intracellular enzymes, that are elevated in plasma in cases of cell damage as; − Damage of the liver cells (both enzymes are elevated) − Myocardial infarction (only AST is elevated). − 5. Types of deamination: Oxidative and non-oxidative 6. Oxidative deamination of amino acids is catalyzed by - L-glutamate dehydrogenase that needs NAD or NADP as a coenzyme - L-amino acid oxidase that needs FMN as a coenzyme - D-amino acid oxidase that needs FAD as a coenzyme 7. Non-oxidative deamination occurs for hydoxy containing amino acids and needs pyridoxal phosphate as a coenzyme. 8. Sources of ammonia: - - Deamination of amino acids - The action of intestinal bacteria on dietary proteins. - Ammonia produced by renal tubular cells by the action of glutaminase enzyme on glutamine (This ammonia helps in regulation of acid- base balance). 9. Fate of ammonia: - - Formation of non-essential amino acids - Formation of purine and pyrimidine nucleotides - Formation of glutamine in the kidney and brain by the mitochondrial enzyme glutamine synthase. - Formation of urea.  Urea cycle - Site: - Liver (mitochondria and cytoplasm). - Urea level in plasma = 10-50 mg/dl - It is excreted mainly by the kidney - Five amino acids share in urea formation: -Ornithine, N-acetyl glutamate, citrulline, aspartate and arginine. 10. Sources of different atoms of urea: - - First Nitrogen atom from ammonia - The carbon atom from CO2 - Second nitrogen atom from aspartate 11. Aspartic acid is a direct donner of nitrogen during synthesis of urea. 12. Carbamoyl phosphate synthase I is the key enzyme of urea cycle. - It is allosterically activated by N-acetyl glutamate and Mg2+. - NAG synthesis is stimulated by high protein diet. 13. Plasma urea is increased by: - ❖ Pre-renal causes - High protein diet - Gastrointestinal hemorrhage - Increased protein catabolism e.g trauma, starvation & malignancy. - Iatrogenic e.g. urea infusion. ❖ Renal causes as acute and chronic glomerulonephritis. ❖ Post-renal causes due to obstruction of urine flow as in benign prostatic hypertrophy and stone. 14. Importance of glycine amino acid - Purine bases (Carbon atoms No 4, 5 and nitrogen atom No 7 are derived from glycine). - Glutathione (It is a tripeptide formed of 3 amino acids (glutamate, cysteine and glycine). It acts as a hydrogen carrier. - Creatine (methyl-guanido-acetate): It is synthesized from 3 amino acids:- glycine, arginine and methionine and used by muscles in the form of creatine phosphate as a source of energy during muscle exercise. - Heme synthesis (Glycine reacts with succinyl CoA to form heme). - Collagen synthesis. - Bile salts:- Glycine is conjugated with primary bile acids e.g with cholic acid to form glycocholic acid. - Formation of serine by serine hydroxymethyl transferase - Hippuric acid:- Glycine conjugates with toxic benzoate to form the non-toxic hippuric acid. - Neurotransmitter: Glycine acts as inhibitory transmitter in spinal cord.  - Formation of glyoxylic acid. 15. Importance of tyrosine amino acid - Catecholamines (dopamine, noradrenaline and adrenaline) in adrenal medulla and adrenal neurons. - Thyroid hormones (T3,T4) in thyroid gland. - Melanin pigment in the eye, hair and skin. - Phenol, cresol and tyramine: - These are putrefactive substances produced by the action of bacteria present in large intestine on tyrosine. 16. Importance of serine amino acid - Glycine by serine hydroxymethyltransferase. - Cysteine by trans-sulfhydration with homocysteine. - Ethanolamine and choline. - Sphingosine:- Formed of serine and palmitoyl CoA. - Purine and pyrimidine bases:- The beta-carbon is a source of the methyl groups of thymine and of C2 and C8 of purine bases. - Synthesis of phosphoproteins e.g casein. 17. Importance of tryptophan amino acid - Biosynthesis of alanine and acetoacetyl CoA. - Biosynthesis of niacin which is a member of vitamin B-complex - Biosynthesis of serotonin (5-hydroxy tryptamine): - It is a stimulatory neurotransmitter - Biosynthesis of melatonin: - It is a hormone produced by pineal gland (body) - Synthesis of indol and skatol. Reaction of protein metabolism - Conversion of phenylalanine to tyrosine (name the enzyme used and coenzymes) O2 PA Hydroxylase H2O Phenylalanine Tyrosine H4biopterin H2biopterin DHB reductase NADP+ NADPH+H+ The enzyme is phenylalanine hydroxylase The coenzyme is NADP that needs tetrahydropiptrine