Reversible inhibition of sheep liver sorbitol dehydrogenase by the antidiabetogenic drug 2‐hydroxymethyl‐4‐(4‐N,N‐dimethylaminosulfonyl‐1‐piperazino) pyrimidine

FEBS Letters

McKinley-McKee, John S.¹  Lindstad, Rune I.¹ 

[1] Institute of Biochemistry, University of Oslo, P.O. Box 1041, Blindern, N-0316 Oslo, Norway

关键词: Sorbitol;    Diabetes;    SDI 158;    Zinc;    Sheep liver;   

DOI  :  10.1016/S0014-5793(97)00372-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 pK values of 6.6 and 8.0, respectively.

【 授权许可】

Unknown