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Reversible inhibition of sheep liver sorbitol dehydrogenase by the antidiabetogenic drug 2‐hydroxymethyl‐4‐(4‐ N , N ‐dimethylaminosulfonyl‐1‐piperazino) pyrimidine
Author(s) -
Lindstad Rune I.,
McKinley-McKee John S.
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00372-4
Subject(s) - sorbitol dehydrogenase , sorbitol , pyrimidine , chemistry , hydroxymethyl , enzyme , stereochemistry , deprotonation , ternary complex , protonation , dehydrogenase , fructose , biochemistry , organic chemistry , ion
The mechanism of the inhibition of sheep liver sorbitol dehydrogenase by the novel antidiabetogenic drug 2‐hydroxymethyl‐4‐(4‐ N , N ‐dimethylaminosulfonyl‐1‐piperazino)pyrimidine has been investigated by steady‐state kinetics over the range pH 5–10. The pyrimidine derivative exhibits mixed inhibition with respect to sorbitol, fructose and coenzyme, due to the formation of enzyme‐inhibitor and enzyme‐NAD(H)‐inhibitor complexes. The formation of each of the binary and ternary complexes is inhibited by protonation and deprotonation of groups which, in the enzyme‐inhibitor complex, have p K values of 6.6 and 8.0, respectively.