Amino Acid Metabolism PDF

By Rania Elsayed Hussein Professor of Medical Biochemistry & Molecular Biology  Glutamic Acid  Non-essential  Glucogenic  Glutamic Acid (Synthesis)  Non-essential From α-KG Transamination reactions: (ALT & AST)...

By Rania Elsayed Hussein Professor of Medical Biochemistry & Molecular Biology  Glutamic Acid  Non-essential  Glucogenic  Glutamic Acid (Synthesis)  Non-essential From α-KG Transamination reactions: (ALT & AST) 2  Glucogenic 1 Reversal of oxidative deamination by GDH  Glutamic Acid (Synthesis)  Non-essential 3 Catabolism of Arginine Arginine & Proline Proline Histidine 4 Cleavage of N-formimino glutamate from catabolism of Histidine  Decarboxylation G Protein GABA L Deamination & synthesis of AA - Blood clotting Carboxylation U - Osteocalcin T Synthesis of NAG A Glutathione Synthesis of Glutamine, M Arginine, Proline A NH3 Acidosis & Hyperammonemia T Glucose E Glutaminase Gtn synthetase ATP NH3 G Protein L Amide group U T Purines & Pyrimidines Metabolic A Derivatives & M Asparagine function of I Amino sugars N Glutamate E NAD+ & NADP+  Metabolic Derivatives of Glutamate PLP  Glutamine is split by glutaminase in renal tubules to excrete NH3 (NH4+) in urine(60%) particularly in acidosis and hyperammonemia.  Metabolic Derivatives & function of Glutamate α-KG Glucose NAG GABA Glutathione Arginine Glutamine  Glycine Tryptophan BCAAs Tyrosine Glutamic acid Phenylalanine Cysteine Methionine Metabolism of Sulfur containing AAs  Non-essential  Glucogenic  Cysteine  Non-essential Trans-sulfuration reaction CH2 – OH CH2 – SH CH-NH2 CH-NH2 COOH COOH Serine cysteine Cystathionine CH2 – S – CH2 + synthase CH-NH2 CH2 Cystathionase H2O/ PLP CooH CH-NH2 H2O/ PLP COOH CH2 – SH Cystathionine CH2 – OH CH2 CH2 CH-NH2 CH-NH2 COOH COOH Homocysteine homoserine  Cysteine  Glucogenic H2O NH3 CH2 – SH CH3 CH3 CH-NH2 PLP C = NH C=O COOH H2S COOH COOH Cysteine α – iminopropionate Pyruvate  Cysteine Synthesis of Conjugation SH 2T with AAs 1) Active site of 1) Thioethanolamine 1) + Cysteine= many enzyme Cystine 2) Taurine 2) +(GLU + Glycine) 2) Sulphate donor (PAPS) = GSH  Cysteine SH Function &Metabolic derivatives 1) Active site of many enzyme 2-Active sulfate (PAPS) Sulfate donor for: - Synthesis of sulfate containing compounds e.g. GAGs & sulfolipids - Detoxification  Cysteine Thioethanolamine Function &Metabolic derivatives Synthesis of Cysteine is decarboxylated to Thioethanolamine 2T Component of: 1) Thioethanolamine Coenzyme A Fatty acid synthase complex 2) Taurine  Cysteine Taurine Function &Metabolic derivatives Synthesis of 2T 1) Thioethanolamine 2) Taurine Taurine (mainly in liver)  Cysteine Synthesis of Conjugation SH 2T with AAs 1) Active site of 1) Thioethanolamine 1) + Cysteine= many enzyme Cystine 2) Taurine 2) +(GLU + Glycine) 2) Sulphate donor (PAPS) = GSH  Cysteine Function &Metabolic derivatives Cysteine Cysteine Cystine  Cysteine Function &Metabolic derivatives Glutamic Cysteine Glycine Glutathione acid  Cysteine Function &Metabolic derivatives Forms of Glutathione  Cysteine Function &Metabolic derivatives Functions of Glutathione A P C D 3 2 1 Cofactor for 4 Powerful AA transport many Detoxication antioxidant enzymes Functions of Glutathione A 1 AA transport Functions of Glutathione P 2 Powerful antioxidant Functions of Glutathione C *Aconitase (TCA cycle) *Glutathione insulin transhydrogenase 3 *Maleylacetoacetate isomerase (Tyrosine metabolism) Cofactor for many * Prostaglandin synthase enzymes Functions of Glutathione D Aromatic compounds e.g.bromobenzene 4 Detoxication  Cysteine Function &Metabolic derivatives Functions of Glutathione A P C D 3 2 1 Cofactor for 4 Powerful AA transport many Detoxication antioxidant enzymes  Cysteine Synthesis of Conjugation SH 2T with AAs 1) Active site of 1) Thioethanolamine 1) + Cysteine= many enzyme Cystine 2) Taurine 2) +(GLU + Glycine) 2) Sulphate donor (PAPS) = GSH  Cysteine Cystinuria (Cystine-lysinuria) Cystinosis Cause The most common genetic error of AA transporter Defect in the Transporter of Dibasic amino acids (cystine, ornithine , arginine & lysine) [COAL] Biochemical basis Failure of transport of these amino acids across the renal proximal tubules and are excreted in urine Manifestations Cystine precipitates in renal tubules, crystallizes and form cystine stones. Treatment Plenty fluids & Alkalinization of urine Cause Genetic lysosomal storage disease caused by a defect in an lysosomal storage disease integral protein called cystinosin which is responsible for transport of cystine across the cell membrane. Biochemical basis Cystine within lysosomes of cells ystine Accumulation of the Manifestations Crystals that can build up and damage the cells particularly the reticuloendothelial cells, kidney and eyes. Accompanied by Generalized aminoaciduria Infants usually die at early age from Renal Failure. 1-Non-essential: - Carbon skeleton from (serine) - Thiol group from (homocysteine) from methionine 2-Glucogenic: by desulfhydrase pyruvate 3-Function: 2 SH 2 by decarboxylase 2 by conjugation with other aa 4-Disorders : Cystinuria Cystinosis Metabolism of Sulfur containing AAs  Methionine Essential Glucogenic  Methionine Glucogenic Oxidative decarboxylation  Methionine Function &Metabolic derivatives Protein Succinyl-CoA Polyamines Glucose Methionine Transsulfuration reaction Methyl Cysteine donor  Formation of polyamins (polycationic) +charges=DNA & RNA (polyanionic) stabilization Growth factor in cell culture Gene expression Methionine Adenosyl transferase Methyl acceptor SAM Methyl product Ethanolamine choline Norepinephrine epinephrine Guanidoacetic acid creatine N-acetylserotonin melatonin Carnosine anserine Nicotinamide N-methylnicotinamide SAH  synthase Methionine Remethylation reaction Remethylation pathway Transsulfuration pathway Methionine Caused by defect in Trans- Homocysteine sulfuration pathway Re-methylation pathway Homocysteine Deficiency of: Methionine Folic acid or/and Vitamin B12 Cysteine Deficiency of : Cystathionine synthase Vitamin B6 (PLP)   High levels of homocysteine and methionine accumulate in tissues& blood (Homocysteinemia) High levels of homocystine cause Modifications of LDL & collagen leading to: Atherogenesis, thrombo-embolic manifestations Osteoporosis Dislocation or complete detachment of the eye lens Mental retardation High plasma and urinary levels of homocystine Homocystinuria 1-Diet in case of trans-sulfuration defect -Low in methionine -High in cysteine 2-Vitamins supplementation (B6, B12 and folate)