Inborn errors of amino acid metabolism

Inherited disorders of amino acid metabolism e.g. phenylketonuria, maple syrup urine disease, alkaptonuria, homocystinuria, Hartnup disease etc for medical, biochemistry and biology undergraduates

1. R. C. Gupta Professor and Head Department of Biochemistry National Institute of Medical Sciences Jaipur, India Inborn Errors of Amino Acid Metabolism

2. E M B - R C G Inborn errors of metabolism occur when some enzyme involved in metabolism is abnormal The abnormality occurs due to a mutation in gene encoding the enzyme The affected enzyme may be absent or deficient

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4. E M B - R C G Over 50 inborn errors of metabolism of amino acids have been discovered The clinical abnormalities may occur due to: Decreased synthesis of products Accumulation of intermediates Formation of alternate metabolites

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7. E M B - R C G Primary hyperoxaluria

8. E M B - R C G Glyoxylate is converted into oxalate when: Glycine transaminase is deficient This leads to hyperoxaluria and recurrent formation of oxalate stones in urinary tract Oxidation of glyoxylate is impaired

9. E M B - R C G Maple syrup urine disease (MSUD)

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11. The enzyme deficiency leads to accumu-lation and increased urinary excretion of: Branched chain amino acids Their a -keto acid derivatives This imparts a typical odour to urine similar to that of maple syrup or burnt sugar

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15. E M B - R C G Cystinuria

16. E M B - R C G Homocystinuria

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18. E M B - R C G The clinical features of homocystinuria are: Thrombotic phenomena Osteoporosis Dislocation of lenses in the eyes Mental retardation Ischaemic vascular disease

19. E M B - R C G Accumulation of homocysteine causes: Abnormal cross-linking of collagen Abnormalities in the ground substance of walls of blood vessels Increased platelet adhesiveness

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21. E M B - R C G Increased platelet adhesiveness and abnormal vessel walls cause: Ischaemic heart disease Cerebral thrombosis Peripheral vascular disease

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25. E M B - R C G Phenylketonuria (PKU)

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27. E M B - R C G One third of the cases are due to a defect in : Dihydropteridine reductase or Conversion of GTP into tetrahydrobiopterin

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29. E M B - R C G The alternate metabolites include: Phenylpyruvate Phenyl-lactate Phenylacetate Phenylacetylglutamine

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35. E M B - R C G Hence, tyrosine becomes an essential amino acid for patients with PKU Their diet needs tyrosine supplements Tyrosine cannot be synthesized endo- genously in PKU

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37. E M B - R C G Tetrahydrobiopterin is also required for hydroxylation of tyrosine and tryptophan Deficiency of tetrahydrobiopterin results in decreased synthesis of: Dopamine, norepinephrine and epinephrine from tyrosine Serotonin and melatonin from tryptophan

38. E M B - R C G The clinical abnormalities in phenyl-ketonuria , types II and III: Are more severe Appear early Do not improve despite diet manipulation

39. E M B - R C G Alkaptonuria is an inborn error of tyrosine metabolism It is due to absence of homogentisate oxidase Homogentisate , an intermediate in cata-bolism of tyrosine, cannot be metabolised further Alkaptonuria

40. E M B - R C G Homogentisate is excreted in urine Freshly voided urine is normal in colour Urine becomes dark on exposure to air due to oxidation of homogentisate by oxygen

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44. E M B - R C G Tyrosinaemia

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47. E M B - R C G Albinism

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50. E M B - R C G Histidinaemia

51. E M B - R C G Histidine is converted into some alternate metabolites: Imidazole pyruvate Imidazole lactate Imidazole acetate The alternate metabolites are excreted in urine

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54. E M B - R C G Hartnup disease

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57. E M B - R C G Decreased availability of tryptophan decreases endogenous synthesis of niacin This may produce a pellagra-like picture The treatment consists of a high-protein diet and niacin supplements

58. Thank you