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PMID: 4462577 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in developing rat and human brain.

The Biochemical journal ·Vol. 144 ·No. 1 ·1974-10-00 ·Pages 91-7

Patel MS

Abstract

1. The effect of the branched-chain amino acids, namely leucine, isoleucine and valine and their corresponding 2-oxo acids on the metabolism of 2-oxoglutarate by developing rat and human brain preparations was investigated. 2. The decarboxylation of 2-oxo[1-(14)C]glutarate to (14)CO(2) by mitochondria from adult rat brain was inhibited by the branched-chain 2-oxo acids whereas the branched-chain amino acids had no inhibitory effect on this process. 3. The activity of 2-oxoglutarate dehydrogenase complex was about 0.2unit/g of brain from 2-day-old rats and increased by about fourfold reaching an adult value by the end of the third postnatal week. 4. The K(m) value for 2-oxoglutarate of the 2-oxoglutarate dehydrogenase complex in rat and human brain was 100 and 83mum respectively. 5. The branched-chain 2-oxo acids competitively inhibited this enzyme from suckling and adult rats brains as well as from foetal and adult human brains, whereas the branched-chain amino acids had no effect on this enzyme. 6. Approximate K(i) values for the branched-chain 2-oxo acids found for this enzyme were in the range found for these 2-oxo acids in plasma from patients with maple-syrup-urine disease. 7. The possible significance of the inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in brains of untreated patients with maple-syrup-urine disease is discussed in relation to the energy metabolism and the biosynthesis of lipids from ketone bodies.

MeSH Terms
Age Factors Animals Brain/enzymology,growth & development Carbon Dioxide/biosynthesis Decarboxylation Humans Isoleucine/pharmacology Keto Acids/pharmacology Ketoglutarate Dehydrogenase Complex/antagonists & inhibitors,metabolism Ketone Oxidoreductases/antagonists & inhibitors Kinetics Leucine/pharmacology Maple Syrup Urine Disease/enzymology Mitochondria/metabolism Molecular Conformation Rats Valine/pharmacology
Chemicals
Keto Acids Isoleucine Carbon Dioxide Ketone Oxidoreductases Ketoglutarate Dehydrogenase Complex Leucine Valine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Patel M S
References (31)
31 references, click to expand
  1. Serotonin depletion by dietary leucine.
    Nature. 1965 Oct 2;208(5005):83-4 PMID: 5886691
  2. Maple syrup urine disease; an inborn error of the metabolism of valine, leucine, and isoleucine associated with gross mental deficiency.
    Br Med J. 1959 Jan 10;1(5114):90-1 PMID: 13608087
  3. Maple syrup disease. Effects of dietary therapy on cerebral lipids.
    Arch Neurol. 1967 May;16(5):486-91 PMID: 6022529
  4. Further observations on the biochemical lesion in maple syrup urine disease.
    Nature. 1967 Apr 15;214(5085):276 PMID: 6034241
  5. The inhibition of malate, tricarboxylate and oxoglutarate entry into mitochondria by 2-n-butylmalonate.
    Biochem Biophys Res Commun. 1967 Jul 21;28(2):249-55 PMID: 4382426
  6. Inhibition of brain protein synthesis: an approach to the biochemical basis of neurological dysfunction in the amino-acidurias.
    Trans N Y Acad Sci. 1966 Nov;29(1):63-70 PMID: 5232222
  7. Development of myelin in inherited disorders of amino acid metabolism.
    Arch Neurol. 1968 Dec;19(6):552-8 PMID: 5726767
  8. Mammalian alpha-keto acid dehydrogenase complexes. IV. Substrate specificities and kinetic properties of the pig heart pyruvate and 2-oxyoglutarate dehydrogenase complexes.
    J Biol Chem. 1969 Mar 10;244(5):1183-7 PMID: 5812959
  9. Free amino acids of fetal brain. Influence of the branched chain amino acids.
    J Neurochem. 1969 Jan;16(1):113-6 PMID: 5776606
  10. Maple syrup urine disease metabolites studies in cerebellum cultures.
    J Neurochem. 1969 Jul;16(7):1141-6 PMID: 5816072
  11. The metabolism of rat brain mitochondria. Preparation and characterization.
    J Biol Chem. 1970 Sep 25;245(18):4724-31 PMID: 4393961
  12. Branched-chain aminotransferase in brain tissue.
    Acta Biochim Pol. 1970;17(2):121-30 PMID: 5486453
  13. Maple syrup urine disease.
    Br Med J. 1959 Jan 10;1(5114):91-3 PMID: 13608088
  14. Maple syrup disease; isolation and identification of organic acids in the urine.
    Pediatrics. 1959 Feb;23(2):348-53 PMID: 13633350
  15. Studies in maple syrup urine disease.
    Arch Dis Child. 1961 Jun;36:259-68 PMID: 13721928
  16. Maple syrup urine disease.
    Arch Dis Child. 1961 Jun;36:269-72 PMID: 13733337
  17. Influence of alpha-ketoacids on the respiration of brain in vitro.
    Proc Soc Exp Biol Med. 1963 Jul;113:660-3 PMID: 13955165
  18. Kinetic studies of rat liver glutamicalanine transaminase.
    J Biol Chem. 1962 Oct;237:3189-95 PMID: 13961700
  19. MAPLE SYRUP URINE DISEASE, WITH PARTICULAR REFERENCE TO DIETOTHERAPY.
    Pediatrics. 1964 Oct;34:454-72 PMID: 14212461
  20. CEREBRAL LIPIDS IN MAPLE SYRUP DISEASE.
    J Pediatr. 1965 Mar;66:584-94 PMID: 14264315
  21. FAMILY SCREENING STUDIES IN MAPLE SYRUP URINE DISEASE (BRANCHED-CHAIN KETOACIDURIA).
    J Pediatr. 1965 Jun;66:1042-8 PMID: 14288457
  22. The inhibition of pyruvate decarboxylation in rat brain by -ketoisocaproic acid.
    Biochem Med. 1971 Apr;5(2):101-8 PMID: 5167175
  23. Studies on the mutual influences of substrates on bovine -keto acid metabolism.
    Biochemistry. 1972 Jun 20;11(13):2416-21 PMID: 5040646
  24. The effect of phenylpyruvate on pyruvate metabolism in rat brain.
    Biochem J. 1972 Jul;128(3):677-84 PMID: 4634834
  25. Effect of the branched-chain alpha-keto acids on pyruvate metabolism by homogenates of human brain.
    J Neurochem. 1973 Jun;20(6):1793-6 PMID: 4719322
  26. Kinetic properties of the partially purified pyruvate dehydrogenase complex of ox brain.
    Biochem J. 1973 Jan;131(1):31-7 PMID: 4352865
  27. Ketone bodies as precursors of sterols and fatty acids in the developing rat.
    J Biol Chem. 1974 Jan 10;249(1):72-80 PMID: 4809632
  28. Development of mitochondrial pyruvate metabolism in rat brain.
    J Neurochem. 1974 May;22(5):709-15 PMID: 4407094
  29. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  30. A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance.
    Pediatrics. 1954 Nov;14(5):462-7 PMID: 13214961
  31. Brain lipids, proteolipids, and free amino acids in maple syrup urine disease.
    J Neurochem. 1966 Sep;13(9):863-74 PMID: 5928229
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj1440091
Published
1974-10-00
Pages
91-7
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1168468
Subset
IM
External Links
PubMed source DOI: 10.1042/bj1440091 PMC Full Text View journal details
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