Acetyl-CoA 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 Krebs Cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester between coenzyme A (a thiol) and acetic acid (an acyl 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 Krebs 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 very central to the balance between carbohydrate metabolism and fat metabolism (see fatty acid synthesis). In normal circumstances, acetyl-CoA from fatty acid metabolism feeds into Krebs 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 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 resevoirs 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.
- Acetyl-CoA is the precursor to HMG-CoA, which, in animals, 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.
- 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 flavonones 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 .
- 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 plants, these include sesquiterpenes, brassinosteroids (hormones), and membrane sterols.
- Krebs Cycle
- HMG-CoA reductase pathway
- Fatty acid metabolism
- Acyl CoA
- Acetyl Co-A synthetase
- Malonyl-CoA decarboxylase