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Noncompetitive, Ca2 ‐independent inhibition of pyruvate dehydrogenase phosphatase by fluphenazine
Author(s) -
Bak ChoongIl,
Huh JaeWook,
Hong Sungyoul,
Song ByoungJoon
Publication year - 1999
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549900202153
Subject(s) - fluphenazine , calmodulin , phosphatase , chemistry , pyruvate dehydrogenase complex , biochemistry , non competitive inhibition , trifluoperazine , enzyme , biology , endocrinology , dopamine , haloperidol
10.1080/15216549900202153.abs The effects of two different classes of calmodulin antagonists on the catalytic activities of purified pyruvate dehydrogenase (PDH) phosphatase and PDH complex (PDC) were studied. In general, PDH phosphatase was more strongly inhibited than PDC by the calmodulin antagonists with the following potency order: fluphenazine>chlorpromazine>thioridazine>trifiupromazine. Promazine and two sulfonamides (W‐5 and W‐7) did not suppress PDH phosphatase activity at 1 mM concentrations, while about 20% of PDC activity was inhibited by these antagonists. Fluphenazine‐mediated inhibition of PDH phosphatase was observed with the purified PDC as well as intact mitochondria. Although Ca2+ stimulates PDH phosphatase activity, the addition of exogenous Ca2+ did not overcome the inhibition by calmodulin antagonists. These results suggest that the suppression of PDH phosphatase activity is dependent upon the structure of the individual calmodulin antagonist and appears to be Ca2+‐independent. Kinetic analysis showed a noncompetitive inhibition of PDH phosphatase by fluphenazine, indicating that it binds to different site(s) from the catalytic site of the enzyme.