Mitochondrial thiamin diphosphate level and the activities of thiamin-dependent enzymes

P. V. Blair, R. Kobayashi, Robert Harris, D. H. Baker, H. M. Edwards, N. F. Shay

Research output: Contribution to journalArticle

Abstract

This study was prompted by our incomplete understanding of the mechanism responsible for the clinical benefits of pharmacological doses of thiamin (T) in .-iomr patients with maple syrup urine, disease and the question of whether thiamin diphosphate (TDP), potent inhibitor of the activity of the protein kinase that phosphorylates and inactivates the branrhed-chain a-ketoacid dehydrogeriH.se (BCKDH) complex, affects the activity state of this complex. Feeding rats a chemically defined. T-deficient diet for ju.st 2 days caused loss of nearly half of the TDP from liver mitochondria. Three more days caused over 70% loss; 3 weeks ovf-r W°/<. Starvation for 1? days had no effect, suggesting a mechanism for conservation of TDP in this nutritional stale. Mitochondria! TDP was higher in rats fed pharmacological -4mounts of T than in rats fed adequate T for maximum growth. Varying dietary T had marked but opposite effects on the activities of a-ketoglutarate dehydrogena.se (KGDH) and BCKDH. T deficiency decreased KGDH activity, increased BCKDH total activity, and increased the proportion of BCKDH in the active, dephosphorylated state. Excess dietary T had ihe opposite effects. More TDP is associated with KGDH than BCKDH in T-deficient rats, suggesting retention of KGDH activity at the expense of BCKDH activity. Thus. T deficiency and excess cause large changes in mitochondrial TDP levels that have rn<ijor effects on the activities of the keto acid dehydrogenasr- complexes. [Supported by the Grace M. Showalter Trust and PUS DK 19-4't (rah p.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1998
Externally publishedYes

Fingerprint

Thiamine Pyrophosphate
Thiamine
thiamin
Rats
Enzymes
enzymes
Mitochondria
rats
Maple Syrup Urine Disease
Pharmacology
maple syrup urine disease
mitochondria
Keto Acids
Liver Mitochondrion
keto acids
Protein Kinase Inhibitors
Nutrition
Starvation
Liver
Protein Kinases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Blair, P. V., Kobayashi, R., Harris, R., Baker, D. H., Edwards, H. M., & Shay, N. F. (1998). Mitochondrial thiamin diphosphate level and the activities of thiamin-dependent enzymes. FASEB Journal, 12(8).

Mitochondrial thiamin diphosphate level and the activities of thiamin-dependent enzymes. / Blair, P. V.; Kobayashi, R.; Harris, Robert; Baker, D. H.; Edwards, H. M.; Shay, N. F.

In: FASEB Journal, Vol. 12, No. 8, 1998.

Research output: Contribution to journalArticle

Blair, PV, Kobayashi, R, Harris, R, Baker, DH, Edwards, HM & Shay, NF 1998, 'Mitochondrial thiamin diphosphate level and the activities of thiamin-dependent enzymes', FASEB Journal, vol. 12, no. 8.
Blair, P. V. ; Kobayashi, R. ; Harris, Robert ; Baker, D. H. ; Edwards, H. M. ; Shay, N. F. / Mitochondrial thiamin diphosphate level and the activities of thiamin-dependent enzymes. In: FASEB Journal. 1998 ; Vol. 12, No. 8.
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