Coenzyme A (A for acyl) participates in activation of acyl groups in general, including the acetyl group derived from pyruvate. The coenzyme is derived metabolically from ATP, the vitamin pantothenic acid, and -mercaptoethylamine (Figure 18.26). A free thiol on the last moiety is the functionally significant part of the coenzyme molecule; the rest of the molecule provides enzyme binding sites. In acylated derivatives, such as acetyl-coenzyme A, the acyl group is linked to the thiol group to form an energy-rich thioester. The acylated forms of coenzyme A will be designated here as acyl-CoA, and the unacylated form as CoA-SH.

The energy-rich nature of thioesters, as compared with ordinary esters, is related primarily to resonance stabilization (Figure 14.9). Most esters can resonate between two forms (Figure 14.9). Stabilization involves Pi-electron overlap, giving partial double-bond character to the C-O link. In thioesters, the larger atomic size of S (as compared with O) reduces the Pi-electron overlap between C and S, so that the C-S structure does not contribute significantly to resonance stabilization. Thus, the thioester is destabilized relative to an ester, so that its G of hydrolysis is increased.

The lack of double-bond character in the C-S bond of acyl-CoAs makes this bond weaker than the corresponding C-O bond in ordinary esters, in turn making the thioalkoxide ion (R-S-) a good leaving group in nucleophilic displacement reactions. Thus, the acyl group is readily transferred to other metabolites, as occurs, in fact, in the first reaction of the citric acid cycle.

Common metabolic reactions involving Coenzyme A are shown below.

1. Acetate + CoASH + ATP <=> Acetyl-CoA + AMP + PPi (catalyzed by Acetate Thiokinase).

2. Pyruvate + NAD⁺ + CoASH <=> Acetyl-CoA + NADH + CO2 (catalyzed by Pyruvate Dehydrogenase).

3. 3-Ketoacyl-CoA + CoASH <=> Acyl-CoA (less 2 carbons) + Acetyl-CoA (catalyzed by Thiolase).

4. Malonyl-CoA + ACP <=> Malonyl-ACP + CoASH (catalyzed by Malonyl-CoA-ACP Transacylase)

5. Acetyl-CoA + ACP <=> Acetyl-ACP + CoASH (catalyzed by Acetyl-CoA-ACP Transacylase)

6. Acyl-CoA + Carnitine <=> Acyl-Carnitine + CoASH (catalyzed by Carnitine Acyltransferase I)

7. Acyl-Carnitine + CoASH <=> Acyl-CoA + Carnitine (catalyzed by Carnitine Acyltransferase II)