AminoAmino AcidsAcids MetabolismMetabolism Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١ http://osp.mans.edu.eg/medbiochem_mi •• CysteineCysteine Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٢ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine SH NH2 CH CH COOH StructureStructure 2 •It is α-amino, β-thiol propionic NutrionalNutrional ValueValue •It is nonnon--essentialessential amino acid MetabolicMetabolic FateFate •It is glucogenicglucogenic amino acid Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٣ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine BiosynthesisBiosynthesis ofof CysteineCysteine Cystathionine NH2 NH2 CH2 CH COOH CH2 CH COOH OH Serine Cystathionine Synthetase S NH2 + PLP CH CH CH COOH SH NH2 2 2 H O CH CH CH COOH 2 2 2 H O Homocysteine 2 PLP Cystathionase Methionine OH NH2 SH NH2 CH2 CH2 CH COOH CH CH COOH + 2 Homoserine Cysteine Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٤ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine MetabolicMetabolic FateFate 1. Incorporated in protein structure • Hormones • Enzymes 2. Biosynthesis of cystine 3. Synthesis of thioethanolamine 4. Biosynthesis of glutathione 5. It gives pyruvic acid 6. Synthesis of glucose 7. Biosynthesis of taurine 8. Bile acids and salts 9. Detoxication Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٥ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 22-- SynthesisSynthesis ofof cystinecystine NH NH2 2 CH2 CH COOH CH2 CH COOH Cysteine reductase SH S SH NH + 2 S NH2 NAD+ NADH.H+ CH2 CH COOH CH2 CH COOH 2 Cysteine Cystine Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٦ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 33-- FormationFormation ofof thioethanolaminethioethanolamine Decarboxylatione SH NH2 SH NH2 CH2 CH COOH CH CH CO2 2 2 Cysteine Thioethanolamine CoA.SH Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٧ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 44-- BiosynthesisBiosynthesis ofof glutathioneglutathione O COOH NH2 CH COOH C NH CH COOH CH2 CH H O + 2 γ Glutamyl cysteine 2 CH2 CH2 NH2 CH2 SH synthetase CH SH 2 CH HC NH γ Glutamyl cysteine 2 2 Cysteine HC NH2 COOH COOH COOH ATP ADP+Pi e Glutamic acid tas Glycine e th yn s ATP e n O O io th C NH CH C NH ta lu CH2 CH2 G ADP+Pi CH2 CH2 SH COOH HC NH2 H2O COOH Glutathione (γ Glutamyl cysteinyl glycine) Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٨ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 55-- FormationFormation ofof pyruvicpyruvic acidacid Desulfhydrase Desulfhydrase SH NH2 NH O CH2 CH COOH CH3 C COOH PLP CH3 C COOH H2S Cysteine H O NH α imino propionic 2 3 Pyruvic acid Transamination Sulpher transferase SH NH2 SH O O CH CH COOH PLP CH C COOH 2 CH2 C COOH 3 α KG Glu 2H H2S Cysteine Thiolpyruvic Pyruvic acid Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٩ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 66-- GlucoseGlucose biosynthesisbiosynthesis Desulfhydrase Cysteine Pyruvic acid Transamination Cysteine Thiolpyruvic Sulfinyl pyruvic Gluconeogenesis Gluconeogenesis Oxidation Cysteine Cysteine sulfinic Glucose Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٠ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 77-- BiosynthesisBiosynthesis ofof taurinetaurine SH NH2 SO2H NH2 Dioxygenase CH2 CH COOH CH2 CH COOH O Cysteine sulfinic Cysteine 2 O NH2 CH2 CH2 SO3H SO H NH 3 2 Decarboxylase SO3H NH2 CH CH 2 2 CH2 CH COOH Taurine CO2 Cysteic acid Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١١ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 88 –– ConjugationConjugation withwith bilebile acidsacids NH CH CH SO H OH + 2 2 2 3 OH C S.CoA C NH CH2CH2 SO3H O O CoA.SH OH HO OH HO H H Taurocoholic Acid Cholyl CoA Na K Na taurocoholate K taurocoholate OH OH SO Na C NH CH2CH2 3 C NH CH2CH2SO3K O O HO OH OH H HO H Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٢ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine Bromophenyl 99-- DetoxicationDetoxication ofof bromophenolbromophenol cysteine S CH2 CH COOH NH2 NH2 HS CH2 CH COOH Acetyl CoA + Br Br Bromophenol CoA.SH S CH2 CH COOH O Bromophenyl HN CCH3 mercapturic Br Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٣ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine Naphthyl 99-- DetoxicationDetoxication ofof naphthalenenaphthalene cysteine NH2 S CH2 CH COOH HS CH2 CH COOH NH2 + Acetyl CoA Naphthalene CoA.SH S CH2 CH COOH O Naphthyl HN CCH mercapturic 3 Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٤ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine CatabolicCatabolic FateFate 1.1. NonoxidativeNonoxidative deaminationdeamination to pyruvic acid 2.2. TransaminationTransamination to Thiolpyruvic acid 3.3. DirectDirect oxidationoxidation to Cysteine sulfinic acid Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٥ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 11--NonoxidativeNonoxidative deaminationdeamination to pyruvic acid Desulfhydrase Desulfhydrase SH NH2 NH O CH2 CH COOH CH3 C COOH PLP CH3 C COOH H2S Cysteine H O NH α imino propionic 2 3 Pyruvic acid Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٦ http://osp.mans.edu.eg/medbiochem_mi 22--TransaminationTransamination to thiolpyruvic acid SH NH2 Cysteine CH2 CH COOH Transaminase SH NADH.H+ O CH2 C COOH Thiolpyruvic 3 mercaptopyruvic Lactate dehydrogenase Sulpher transferase 2H NAD+ O H2S SH OH CH3 C COOH Na Pyruvic acid CH2 CH COOH 3 mercaptolactic Sulphite oxidase Sodium sulphate Na2SO4 Na2SO3 Sodium sulphite Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٧ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine 33-- DirectDirect oxidationoxidation to cysteine sulfinic acid SO2H NH2 Dioxgenase CH2 CH COOH SH NH2 Cysteine sulfinic CH2 CH COOH O2 Cysteine α KG Transaminase Taurine Cysteic acid Glu O Desulfinase SO2H O CH3 C COOH CH2 C COOH Pyruvic acid -- SO3 Sulfinyl pyruvic Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٨ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine Inborn errors of cysteine metabolism •• 11-- CystinuriaCystinuria • Marked increase in urinary cystine, lysine, arginine and ornithine. • Defective renal tubular reabsorption of these amino acids. Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ١٩ http://osp.mans.edu.eg/medbiochem_mi CysteineCysteine Inborn errors of cysteine metabolism •• 22-- CystinosisCystinosis • Cystine accumulates in lysosomes • No transport to cytoplasm • Deposition of cystine crystals in tissues • Impaired renal functions • Generalized amino aciduria • Renal failure Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٢٠ http://osp.mans.edu.eg/medbiochem_mi SelenocysteineSelenocysteine OH NH2 SeH NH2 CH CH COOH 2 CH2 CH COOH • Selenocysteine occurs at the active site of many enzymes: – Glutathione peroxidase – Deiodinase – Thioredoxin reductase • Selenocysteine-tRNA is first charged with serine • Subsequent replacement of the serine oxygen by selenium Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry ٢١ http://osp.mans.edu.eg/medbiochem_mi.