Inhibition of rat brain pyruvate dehydrogenase by thiamine analogs

Charles T. Kandiko, Daniel Smith, Bryan K. Yamamoto

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Abstract

The effects of thiamine thiazolone (TT) and thiamine thiazolone pyrophosphate (TTPP) on the in vitro and in vivo inhibition of pyruvate dehydrogenase complex (PDHC) from rat cortex and hippocampus were characterized. TTPP decreased PDHC activity in vitro but had no effect in vivo following its direct chronic administration via osmotic mini-pumps into the brains of behaving rats. In contrast, TT had no direct effect in vitro following a differential centrifugation purification of the mitochondrial PDHC fraction, but decreased PDHC activity in vivo. Additional experiments demon- strated that the cytosolic fraction converted TT to TTPP which, in turn, inhibited PDHC in vitro. A mechanism is proposed to explain these effects that is consistent with a non-competitive inhibition of brain PDHC by TTPP.

Original languageEnglish (US)
Pages (from-to)4375-4380
Number of pages6
JournalBiochemical Pharmacology
Volume37
Issue number22
DOIs
StatePublished - Nov 15 1988

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ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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