2-Keto-4-methylthiobutyrate, an intermediate in the methionine salvage pathway, is a good substrate for CtBP1

In the present work, we have studied the kinetic properties of the catalytic domain of CtBP1, a co-repressor belonging to the D-2-hydroxyacid dehydrogenase family and known to reduce pyruvate in the presence of NADH. CtBP1 acted on a variety of alpha-keto acids, for which it displayed biphasic curves with inhibition at elevated concentrations, as observed with other dehydrogenases of the same family. Based on catalytic efficiencies, the best substrate was 2-keto-4-methylthiobutyrate, an intermediate of the methionine salvage pathway. It was about 20-fold better than 2-ketoisocaproate and glyoxylate, and 80-fold better than pyruvate. From these data we conclude that 2-keto-4-methylthiobutyrate may be an important regulator of CtBP activity, possibly linking gene repression to the activity of the methionine salvage and spermine synthesis pathways. (c) 2006 Elsevier Inc. All rights reserved.