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

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.