Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical
reactions.
It is referred to as the "Hub of Metabolism".
Its main function is to convey the carbon atoms within the acetyl group to the citric
acid cycle to be oxidized for energy production.
Structure of coenzyme A consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid
through an amide linkage.
The acetyl group of acetyl-CoA is linked by a "high energy" thioester to the sulfhydryl
portion of the β-mercaptoethylamine.It is this thioester bond that makes acetyl-CoA
one of the "high energy" compounds.
Hydrolysis of the thioester bond is highly exergonic.
Acetyl-CoA is produced during breakdown of carbohydrates through glycolysis as well as
fatty acid oxidation and 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.
Konrad Bloch and Feodor Lynen were awarded the 1964 Nobel Prize in Physiology and Medicine
for their discoveries linking acetyl-CoA and fatty acid metabolism.
Fritz Lipmann won the Nobel Prize in 1953 for his discovery of the cofactor Coenzyme
A.
Functions 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.
Direct synthesis The two components of acetyl-CoA—the acetyl,
supplied via acetate, and Coenzyme-A groups—can be linked directly, catalyzed by the enzyme
acetyl—CoA synthetase.
This process is involved in metabolism of carbon sugars.
As a starting point for the citric acid cycle, the acetyl—Co-A synthetase route is less
common than the pyruvate dehydrogenase route.
Fatty acid metabolism In animals, acetyl-CoA and other acyl-CoA
coenzymes are essential to the balance between carbohydrate metabolism and fat metabolism.
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, which is different from 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.
Other reactions Two acetyl-CoA molecules can be condensed
to create acetoacetyl-CoA, the first step in the HMG-CoA reductase/mevalonic acid pathway,
leading to synthesis of isoprenoids.
In animals, HMG-CoA is a vital precursor to cholesterol and ketone body synthesis.
Acetyl-CoA is also the source of the acetyl group incorporated onto certain lysine residues
of histone and nonhistone proteins in the posttranslational 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 then 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, and membrane sterols.
Interactive pathway map Click on genes, proteins and metabolites below
to visit Gene Wiki pages and related Wikipedia articles.
The pathway can be downloaded and edited at WikiPathways.
See also Malonyl-CoA decarboxylase
References
External links Acetyl Coenzyme A at the US National Library
of Medicine Medical Subject Headings