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Text
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URL Address
<a href="http://doi.org/10.1016/0006-2952(88)90620-x" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/0006-2952(88)90620-x</a>
Pages
4375–4380
Issue
22
Volume
37
Dublin Core
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Title
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Inhibition of rat brain pyruvate dehydrogenase by thiamine analogs.
Publisher
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Biochemical pharmacology
Date
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1988
1988-11
Subject
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Male; Animals; Rats; Kinetics; Brain/*enzymology; Cerebral Cortex/drug effects/enzymology; Hippocampus/drug effects/enzymology; Pyruvate Dehydrogenase Complex/*antagonists & inhibitors; Thiamine Pyrophosphate/analogs & derivatives/pharmacology; Thiamine/*analogs & derivatives/pharmacology; Inbred Strains
Creator
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Kandiko C T; Smith D; Yamamoto B K
Description
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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 demonstrated 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.
Identifier
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<a href="http://doi.org/10.1016/0006-2952(88)90620-x" target="_blank" rel="noreferrer noopener">10.1016/0006-2952(88)90620-x</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
1988
Animals
Biochemical pharmacology
Brain/*enzymology
Cerebral Cortex/drug effects/enzymology
Hippocampus/drug effects/enzymology
Inbred Strains
Kandiko C T
Kinetics
Male
Pyruvate Dehydrogenase Complex/*antagonists & inhibitors
Rats
Smith D
Thiamine Pyrophosphate/analogs & derivatives/pharmacology
Thiamine/*analogs & derivatives/pharmacology
Yamamoto B K