Interaction of Long‐Chain Acyl‐CoA Analogs with Pig Kidney General Acyl‐CoA Dehydrogenase

Abstract

The interaction of two long‐chain acyl‐CoA analogs with pig kidney general acyl‐CoA dehydrogenase (EC 1.3.99.3) was examined. The effect of S‐heptadecyl‐CoA and heptadecan‐2‐onyl‐dethio‐CoA on the flavoprotein was observed spectrophotometrically using the flavin as an active‐site probe. The S‐heptadecyl thioether analog bound strongly to the enzyme (Kd= 17 nM) and was a powerful competitive inhibitor (Ki < 40 nM). In contrast to the thioether analog, the dethiocarba derivative, heptadecan‐2‐onyl‐dethio‐CoA, was a substrate in the standard assay system being dehydrogenated at about 60% of the rate shown by palmitoyl‐CoA. These results support the proposal that α‐carbanion formation is an early event in the dehydrogenation of acyl‐CoA substrates. Copyright © 1981, Wiley Blackwell. All rights reserved