Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidization of fatty acids, and the oxidation of pyruvate in the citric acid cycle. It is adapted from β-mercaptoethylamine, panthothenate and adenosine triphosphate.
The main function of coenzyme A is to carry acyl groups (such as the acetyl group) or thioesters. A molecule of coenzyme A carrying an acetyl group is also referred to as acetyl-CoA. It is sometimes referred to as 'CoASH' or 'HSCoA' because when it is not attached to a molecule such as an acetyl group, it is attached to a thiol group, -SH.
Acetyl-CoA is an important molecule itself. It is the precursor to HMG CoA, which is a vital component in cholesterol and ketone synthesis. Furthermore, it contributes an acetyl group to choline to produce acetylcholine, in a reaction catalysed by choline acetyltransferase. Its main task is conveying the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production.
Pyruvate Dehydrogenase Reaction
The conversion of pyruvate into acetyl-CoA is referred to as the Pyruvate Dehydrogenase Reaction. It is catalyzed by an enzyme-complex called pyruvate dehydrogenase. The enzyme consists of 60 subunits: 24 pyruvate dehydrogenase, 24 dihydrolipoyl transacetylase, and 12 dihydrolipoyl dehydrogenase (commonly denoted E1, E2, and E3). 24 pyruvate dehydrogenase has the coenzyme TPP (thiamin pyrophosphate) incorporated into it, 24 dihydrolipoyl transacetylase has lipoate and coenzyme A, and 12 dihydrolipoyl dehydrogenase has the coenzymes FAD and NAD+. Through a complex reaction, pyruvate is decarboxylated and turned into acetaldehyde, then attached to coenzyme A while NAD+ is subsequently reduced to NADH and H+.
Coenzyme A is very central to the balance between carbohydrate metabolism and fat metabolism. Normally, acetyl-CoA from fatty acid metabolism feeds into the citric acid cycle, contributing to the cell's energy supply. In the liver, when levels of circulating fatty acids are high, the production of acetyl-CoA from fat breakdown exceeds the cellular energy requirements. To make use of the energy available from the excess acetyl-CoA, ketone bodies are produced which can then circulate in the blood.
In some circumstances this can lead to an excess of ketone bodies in the blood, a condition known as ketosis. This can occur in diabetes, starvation or in people following low-carbohydrate diets, all of which can cause fats to be metabolised as a major source of energy.