is an important molecule in metabolism, used in many biochemical reactions. Its main use is to convey the carbon atoms
within the acetyl
group to the citric acid cycle
to be oxidized
for energy production. In chemical structure, acetyl-CoA is the thioester
between coenzyme A
) and acetic acid
group carrier). Acetyl-CoA is produced during the second step of aerobic cellular respiration
, pyruvate decarboxylation
, which occurs in the matrix
of the mitochondria
. Acetyl-CoA then enters the citric acid cycle.
Acetyl-CoA is also an important component in the biogenic synthesis of the neurotransmitter acetylcholine. Choline, in combination with Acetyl-CoA, is catalyzed by the enzyme choline acetyltransferase to produce acetylcholine and a coenzyme a byproduct.
Pyruvate dehydrogenase and pyruvate formate lyase reactions
The oxidative conversion of pyruvate
into acetyl-CoA is referred to as the pyruvate dehydrogenase reaction
. It is catalyzed by the pyruvate dehydrogenase complex
. Other conversions between pyruvate and acetyl-CoA are possible. For example, pyruvate formate lyase
disproportionates pyruvate into acetyl-CoA and formic acid
. The pyruvate formate lyase reaction does not involve any net oxidation or reduction.
Fatty acid metabolism
In animals, acetyl-CoA is central to the balance between carbohydrate metabolism
metabolism (see fatty acid synthesis
). In normal circumstances, 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 the presence of very high levels of ketone bodies in the blood, a condition called ketosis. Benign dietary ketosis can safely occur in people following low-carbohydrate diets, which cause fats to be metabolised as a major source of energy. This is different from ketosis brought on as a result of starvation and ketoacidosis, a dangerous condition that can affect diabetics.
In plants, de novo fatty acid synthesis occurs in the plastids. Many seeds accumulate large reservoirs of seed oils to support germination and early growth of the seedling before it is a net photosynthetic organism. Fatty acids are incorporated into membrane lipids, the major component of most membranes.
- Two acetyl-CoA can be condensed to create acetoacetyl-CoA, the first step in the HMG-CoA/ mevalonic acid pathway leading to synthesis of isoprenoids. In animals HMG-CoA is a vital precursor to cholesterol and ketone synthesis.
- Acetyl-CoA is also the source of the acetyl group incorporated onto certain lysine residues of histone and non-histone proteins in the post-translational modification acetylation, a reaction catalyzed by acetyltransferases.
- In plants and animals, cytosolic acetyl-CoA is synthesized by ATP citrate lyase When glucose is abundant in the blood of animals, it is converted via glycolysis in the cytosol to pyruvate, and thence to acetyl-CoA in the mitochondrion. The excess of acetyl-CoA results in production of excess citrate, which is exported into the cytosol to give rise to cytosolic acetyl-CoA.
- Acetyl-CoA can be carboxylated in the cytosol by acetyl-CoA carboxylase, giving rise to malonyl-CoA, a substrate required for synthesis of flavonoids and related polyketides, for elongation of fatty acids to produce waxes, cuticle, and seed oils in members of the Brassica family, and for malonation of proteins and other phytochemicals
- In plants, these include sesquiterpenes, brassinosteroids (hormones), and membrane sterols.