Acyl‐CoA dehydrogenases

Acyl‐CoA dehydrogenases constitute a family of flavoproteins that catalyze the α,β‐dehydrogenation of fatty acid acyl‐CoA conjugates. While they differ widely in their specificity, they share the same basic chemical mechanism of α,β‐dehydrogenation. Medium chain acyl‐CoA dehydrogenase is probably the best‐studied member of the class and serves as a model for the study of catalytic mechanisms. Based on medium chain acyl‐CoA dehydrogenase we discuss the main factors that bring about catalysis, promote specificity and determine the selective transfer of electrons to electron transferring flavoprotein. The mechanism of α,β‐dehydrogenation is viewed as a process in which the substrate αC‐H and βC‐H bonds are ruptured concertedly, the first hydrogen being removed by the active center base Glu376‐COO– as an H+, the second being transferred as a hydride to the flavin N(5) position. Hereby the pKa of the substrate αC‐H is lowered from > 20 to ≈ 8 by the effect of specific hydrogen bonds. Concomitantly, the pKa of Glu376‐COO– is also raised to 8–9 due to the decrease in polarity brought about by substrate binding. The kinetic sequence of medium chain acyl‐CoA dehydrogenase is rather compl