Unusually High Standard Redox Potential of Acrylyl-CoA/ Propionyl-CoA Couple among Enoyl-CoA/Acyl-CoA Couples: A Reason for the Distinct Metabolic Pathway of Propionyl-CoA from Longer Acyl-CoAs

The standard redox potential of acrylyl-CoA/propionyl-CoA couple (C3) was determined to be 69 mV (vs. standard hydrogen electrode) at pH 7 and 25°C. This value implies that the 2, 3-dehydrogenation of propionyl-CoA is thermodynamically much more unfavorable than that of longer acyl-CoAs because the standard redox potentials of crotonyl-CoA/butyryl-CoA (C4), octenoyl-CoA/octanoyl-CoA (C8), and hexadecenoyl-CoA/palmitoyl-CoA (C16) are all about – lOmV. The unusually high standard redox potential of the acrylyl-CoA/ propionyl-CoA couple is thought to be one of the reasons that in mammals propionyl-CoA is not metabolized by β-oxidation as in the case of longer acyl-CoAs, but by a methyl-malonyl-CoA pathway. The obvious structural difference between C3 and C4 (and longer) is whether an H or the C(4) atom is connected to -C(3)H=C(2)H-C(l)0-S-CoA. The molecular orbital calculations (MOPAC) for the enoyl and acyl forms of C3 and C4 revealed that this structural feature is the main cause for the higher standard redox potential of the C3 couple. That is, the C(4)-C(3) bond is stabilized by the dehydrogenation to a greater degree than the H-C(3) bond.