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Dr.S.Chakravarty MBBS, MD

Metabolism of branched chain amino acids. Dr.S.Chakravarty MBBS, MD . Learning objectives. Discuss the steps in branched chain amino acid metabolism Classify organic a cidurias and differentiate their clinical features . Metabolism of branched chain aminoacids. Valine Leucine

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Dr.S.Chakravarty MBBS, MD

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  1. Metabolism of branched chain amino acids Dr.S.Chakravarty MBBS, MD

  2. Learning objectives • Discuss the steps in branched chain amino acid metabolism • Classify organic acidurias and differentiate their clinical features

  3. Metabolism of branched chain aminoacids • Valine • Leucine • Isoleucine • Metabolized in the muscle • Liver cannot metabolize branched chain aminoacids

  4. Tender – Thiamine Loving - Lipoamide Care -CoASH For – (FAD)Riboflavin Nancy- NAD (Niacin) 3 Enzymes:- 1)PDH, 2)α-KGDH(TCA cycle) 3)Branched keto acid dehydrogenase USMLE!! Leucine, Valine and Isoleucine Transaminase Corresponding Alpha ketoacids Alphaketoaciddecarboxylase(branched keto acid dehydrogenase) Many steps Leucine Valine Isovaleryl Co-A Isoleucine Succinyl Co-A Isovaleryl Co-A dehydrogenase Propionyl Co-A +Acetyl CoA Many steps Methylmalonyl Co-A mutase Propionyl Co-A carboxylase Acetoacetyl Co-A + Acetyl CoA Methylmalonyl Co-A

  5. Organic acidemias: • Maple syrup urine disease • Isovalericacidemia • Propionic-acidemia • Methylmalonic acidemia • Common features – • ketosis, acidosis – accumulation of organic acids • Hyperammonemia - accumulation of CoA derivatives of organic acids, which inhibit the formation of N -acetylglutamate, the activator of carbamoyl phosphate synthetase in liver.

  6. Maple syrup urine disease • Def of enzyme Alpha ketoaciddecarboxylase /dehydrogenase • Branched chain ketones in urine • Acidosis, mental retardation, convulsions, coma-->extensive brain damage • Death by end of 1 year • Urine smells of burnt sugar (maple syrup). • Diagnosis – Chromatography 2,4-DNPH test  yellow ppt.

  7. Isovalericacidemia • Def of enzyme – isovaleryl co-A dehydrogenase • Cheesy odour – isovaleric acid • Distinctive odour of ‘sweaty feet’ • Vomiting, acidosis, convulsions and coma

  8. Propionicacidemia • Def of enzyme Propionyl Co-A carboxylase • Increase in propionic acid levels. • Required for metabolism of isoleucineand odd chain fatty acids • Vomiting, acidosis, ketosis, hypotonia and coma • Accumulation of odd chain fatty acids in liver.

  9. Methylmalonicacidemia • Def of enzyme methyl malonyl Co-A mutase • Dependent on B12 • Two forms :- • Response to pharmacological doses of B12 • Response to Massive doses of B12 • Accumulation of methylmalonic acid  Neurotoxin. • Demyelination – due to abnormal fatty acid accumulation in myelin

  10. Thank you

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