Medical Biochemistry II PDF

Medical Biochemistry II Synthesis of non-essential amino acids from glycolysis intermediates SMU - Internal Data Student Learning outcomes SMU - Internal Data SMU - Internal Data Overview Degradation of amino acids A. Gluconeogenic: converted to glucose via gluconeogenesis Blue are B. Ketogenic: con...

Medical Biochemistry II Synthesis of non-essential amino acids from glycolysis intermediates SMU - Internal Data Student Learning outcomes SMU - Internal Data SMU - Internal Data Overview Degradation of amino acids A. Gluconeogenic: converted to glucose via gluconeogenesis Blue are B. Ketogenic: converted to ketone bodies both Two of the essential amino acids (lysine and leucine) are strictly ketogenic. The amino acids synthesized from TCA cycle intermediates (aspartate, asparagine, glutamate, glutamine, proline, and arginine) are reconverted to these intermediates during degradation SMU - Internal Data Fig. 2 Amino Acids Derived From Intermediates of Glycolysis: 1. Serine 3-phosphoglycerate NAD+ NADH Phosphoglycerate DH 3-phosphohydroxy pyruvate glutamate B6 Phosphoserine amino transferase Alphaketoglutarate 3-phosphoserine Phosphoserine phosphotase Serine SMU - Internal Data Serine to glycine Serine catabolism Serine to cysteine Serine back to glycolysis -ORSerine SMU - Internal Data PLP (B6) Ethanolamine CO2 Amino Acids Derived From Intermediates of Glycolysis: 2. Glycine *One-carbon metabolism donates methyl group to THF *deletion 17p11.2: lack enzyme = Smith-Magenis Syndrome: 1. Behavioral problems 2. Growth delay 3. Speech delay 4. Psychomotor deficiency Serine (3) * * Serine THF hydroxymethyl N5N10 – transferase THF N5N10 – methylene THF methylene THF Glycine (2C) Glysine decarboxylase (cleavage complex) NH4+ + CO2 SMU - Internal Data THF M in o rr ou PLP te N5N10 – methylene THF Threonine Essential AA (2C) Glycine: Cleavage complex P subunit – glycine dehydrongenase (requires pyridoxal-P) H subunit – Lippoic acid T subunit – tetrahydrofolate requiring aminomethyl transferase L subunit – dihydrolipoamide DH Encoded by the DLD gene (7q31-q32) DLD is required also for: PDH complex Alpha ketoglutarate DH complex Branched-chain keto-acid DH complex SMU - Internal Data Glycine: catabolism The conversion of glycine to glyoxylate by the enzyme D-amino acid oxidase is a degradative pathway of glycine that is medically important Once glyoxylate is formed, it can be oxidized to oxalate, which is sparingly soluble and tends to precipitate in kidney tubules, leading to kidney stone formation Kidney stones B6 B6 SMU - Internal Data 3. Cysteine Sulfur is from the essential AA methionine Synthesis is clinically relevant Several vitamins are required: 1. Folate 2. B6 (PLP, pyridoxal P) 3. B12 SMU - Internal Data 3. Cysteine: synthesis + serine Beta synthase ** proteins cystathione Succinyl-CoA Cystathione lyase Glutathione SMU - Internal Data Cystine + alph-ketobuterate Propionyl-CoA 3. Cysteine: degradation Decarboxylase Hypotaurine Taurine Bile salts SMU - Internal Data Co-enzyme in sulfur transferase reactions Active sulfur 3. Cysteine: importance Proteins Glutathione production Taurine production (modifies bile salts: taurocholate and taurochenodeoxycholate) Sulfur is activated to form PAPS (3’-phosphoadenosine 5’phosphosulfate) used as a Sulfate donor in modifying carbs and proteins Sulfur is source for coenzyme-A synthesis SMU - Internal Data Homocysteinemia/Homocystinuria Defect in conversion of methionine to cysteine. Result: elevated levels of homocysteine and homocystine in blood Most common cause: defects in cystathionine Beta-synthase (CBS) gene defects Associated with mental retardation SMU - Internal Data Amino Acids Derived From Intermediates of Glycolysis: 4. Alanine Urea cycle NH4 SMU - Internal Data