Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many
biochemical reaction
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
s in protein, carbohydrate and lipid
metabolism. Its main function is to deliver the
acetyl
In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...
group to the
citric acid cycle (Krebs cycle) to be
oxidized for energy production.
Coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
(CoASH or CoA) consists of a
β-mercaptoethylamine group linked to the vitamin
pantothenic acid (B5) through an
amide linkage
In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein chai ...
and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the
sulfhydryl
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
substituent of the β-mercaptoethylamine group. This
thioester linkage is a "high energy" bond, which is particularly reactive.
Hydrolysis of the thioester bond is
exergonic (−31.5 kJ/mol).
CoA is acetylated to acetyl-CoA by the breakdown of
carbohydrates
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or may ...
through
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
and by the breakdown of
fatty acids through
β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released is captured in the form of 11
ATP
ATP may refer to:
Companies and organizations
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* American Technical Publishers, employee-owned publishing company
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and one
GTP per acetyl group. GTP is the equivalent of ATP and they can be interconverted by
Nucleoside-diphosphate kinase
Nucleoside-diphosphate kinases (NDPKs, also NDP kinase, (poly)nucleotide kinases and nucleoside diphosphokinases) are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) ...
.
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
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
.
Direct synthesis
The acetylation of CoA is determined by the carbon sources.
Extramitochondrial
* At high
glucose levels,
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
takes place rapidly, thus increasing the amount of
citrate produced from the tricarboxylic acid cycle. This citrate is then exported to other
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
s outside the mitochondria to be broken into acetyl-CoA and
oxaloacetate by the
enzyme ATP citrate lyase (ACL). This principal reaction is coupled with the hydrolysis of ATP.
* At low glucose levels:
** CoA is acetylated using
acetate
An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...
by
acetyl-CoA synthetase (ACS), also coupled with
ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
hydrolysis.
**
Ethanol also serves as a carbon source for acetylation of CoA utilizing the enzyme
alcohol dehydrogenase.
** Degradation of branched-chain
ketogenic amino acids such as
valine,
leucine, and
isoleucine
Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...
occurs. These amino acids are converted to α-ketoacids by
transamination and eventually to isovaleryl-CoA through oxidative decarboxylation by an α-ketoacid dehydrogenase complex. Isovaleryl-CoA undergoes
dehydrogenation,
carboxylation and hydration to form another CoA-derivative intermediate before it is cleaved into acetyl-CoA and
acetoacetate
Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound with the formula CHCOCHCOOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite stab ...
.
Intramitochondrial

* At high glucose levels, acetyl-CoA is produced through
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
.
Pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic aci ...
undergoes oxidative decarboxylation in which it loses its
carboxyl group (as
carbon dioxide) to form acetyl-CoA, giving off 33.5 kJ/mol of energy. The oxidative conversion of pyruvate into acetyl-CoA is referred to as the pyruvate dehydrogenase reaction. It is catalyzed by the
pyruvate dehydrogenase complex
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and t ...
. Other conversions between pyruvate and acetyl-CoA are possible. For example,
pyruvate formate lyase
In enzymology, formate C-acetyltransferase (''pyruvate formate lyase'') () is an enzyme. Pyruvate formate lyase is found in ''Escherichia coli'' and other organisms. It helps regulate anaerobic glucose metabolism. Using radical non-redox chemistry ...
disproportionates pyruvate into acetyl-CoA and
formic acid
Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid, and has the chemical formula HCOOH and structure . It is an important intermediate in chemical synthesis and occurs naturally, most notably in some ants. Es ...
.

* At low glucose levels, the production of acetyl-CoA is linked to
β-oxidation of
fatty acids. Fatty acids are first converted to acyl-CoA. Acyl-CoA is then degraded in a four-step cycle of oxidation, hydration, oxidation and
thiolysis catalyzed by four respective enzymes, namely
acyl-CoA dehydrogenase,
enoyl-CoA hydratase
Enoyl-CoA hydratase (ECH) or crotonase is an enzyme that hydrates the double bond between the second and third carbons on 2-trans/cis-enoyl-CoA:
ECH is essential to metabolizing fatty acids in beta oxidation to produce both acetyl CoA and e ...
,
3-hydroxyacyl-CoA dehydrogenase
In enzymology, a 3-hydroxyacyl-CoA dehydrogenase () is an enzyme that catalyzes the chemical reaction
:(S)-3-hydroxyacyl-CoA + NAD+ \rightleftharpoons 3-oxoacyl-CoA + NADH + H+
Thus, the two substrates of this enzyme are (S)-3-hydroxyacyl-Co ...
, and
thiolase. The cycle produces a new fatty acid chain with two fewer carbons and acetyl-CoA as a byproduct.
Functions
Intermediates in various pathways
* In Cellular Respiration
*
Citric acid cycle:
** Through a series of chemical reactions, stored energy is released through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into
adenosine triphosphate (ATP) and
carbon dioxide.
*
Fatty acid metabolism
Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes ...
** Acetyl-CoA is produced by the breakdown of both
carbohydrates (by
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
) and
lipids (by
β-oxidation). It then enters the citric acid cycle in the mitochondrion by combining with
oxaloacetate to form
citrate.
** Two acetyl-CoA molecules condense to form
acetoacetyl-CoA, which gives rise to the formation of
acetoacetate
Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound with the formula CHCOCHCOOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite stab ...
and
β-hydroxybutyrate.
Acetoacetate, β-hydroxybutyrate, and their spontaneous breakdown product
acetone are frequently, but confusingly, known as
ketone bodies
Ketone bodies are water-soluble molecules that contain the ketone groups produced from fatty acids by the liver (ketogenesis). Ketone bodies are readily transported into tissues outside the liver, where they are converted into acetyl-CoA (acetyl- ...
(as they are not "bodies" at all, but water-soluble chemical substances). The ketone bodies are released by the
liver into the blood. All cells with mitochondria can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the
gluconeogenic pathway in the way that the liver does. Unlike free fatty acids, ketone bodies can cross the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
and are therefore available as fuel for the cells of the
central nervous system, acting as a substitute for glucose, on which these cells normally survive.
The occurrence of high levels of ketone bodies in the blood during
starvation
Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, dea ...
, a
low-carbohydrate diet, prolonged heavy exercise, and uncontrolled
type-1 diabetes mellitus is known as
ketosis
Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability, such as low-carbohydrate diets or fasting, that provides an additional ...
, and in its extreme form in out-of-control type-1 diabetes mellitus, as
ketoacidosis.
** On the other hand, when the
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
concentration in the blood is high, and that of
glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
is low (i.e. after meals), the acetyl-CoA produced by glycolysis condenses as normal with oxaloacetate to form citrate in the mitochondrion. However, instead of continuing through the citric acid cycle to be converted to carbon dioxide and water, the citrate is removed from the mitochondrion into the
cytoplasm.
There it is cleaved by
ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion).
This cytosolic acetyl-CoA can then be used to synthesize fatty acids through carboxylation by
acetyl-CoA carboxylase
Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme () that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is ...
into
malonyl CoA, the first committed step in the synthesis of fatty acids.
This conversion occurs primarily in the liver,
adipose tissue and lactating
mammary glands, where the fatty acids are combined with
glycerol to form
triglycerides, the major fuel reservoir of most animals. Fatty acids are also components of the
phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s that make up the bulk of the
lipid bilayers of all
cellular membranes.
** In plants, ''de novo'' fatty acid synthesis occurs in the
plastid
The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the Cell (biology), cells of plants, algae, and some other eukaryotic organisms. They are considered to be intracellular endosy ...
s. Many
seeds accumulate large reservoirs of seed oils to support
germination
Germination is the process by which an organism grows from a seed or spore. The term is applied to the sprouting of a seedling from a seed of an angiosperm or gymnosperm, the growth of a sporeling from a spore, such as the spores of fungi, fer ...
and early growth of the seedling before it is a net
photosynthetic
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored in c ...
organism.
** The
cytosolic acetyl-CoA can also condense with
acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (
HMG-CoA) which is the rate-limiting step controlling the
synthesis of cholesterol.
Cholesterol can be used as is, as a structural component of cellular membranes, or it can be used to synthesize
steroid hormones,
bile salts, and
vitamin D.
** Acetyl-CoA can be
carboxylated in the cytosol by
acetyl-CoA carboxylase
Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme () that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is ...
, giving rise to
malonyl-CoA
Malonyl-CoA is a coenzyme A derivative of malonic acid.
Functions
It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis.
Fatty acid biosynthesis
Malonyl-CoA provides 2-carbon units to fatty acids and commi ...
, a substrate required for synthesis of
flavonoid
Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.
Chemically, flavonoids ...
s and related
polyketides, for elongation of fatty acids to produce
waxes,
cuticle
A cuticle (), or cuticula, is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non- homologous, differing in their origin, structu ...
, 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
sterol
Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...
s.
*
Steroid synthesis
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
:
** Acetyl-CoA participates in the
mevalonate pathway by partaking in the synthesis of
hydroxymethyl glutaryl-CoA
The hydroxymethyl group is the name for a substituent with the structural formula −CH2−OH. It consists of a methylene bridge (−CH2− unit) bonded to a hydroxyl group (−OH). This makes the hydroxymethyl group an alcohol. It has the ide ...
.
*
Acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
synthesis:
** Acetyl-CoA is also an important component in the biogenic synthesis of the
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
.
Choline, in combination with acetyl-CoA, is catalyzed by the enzyme
choline acetyltransferase
Choline acetyltransferase (commonly abbreviated as ChAT, but sometimes CAT) is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme acetyl-Co ...
to produce acetylcholine and
coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
as a byproduct.
*
Melatonin
Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle.
In vertebrates ...
synthesis
* Acetylation
** Acetyl-CoA is also the source of the acetyl group incorporated onto certain
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
residues of
histone and nonhistone proteins in the
posttranslational modification acetylation
:
In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
. This acetylation is catalyzed by
acetyltransferases
Acetyltransferase (or transacetylase) is a type of transferase enzyme that transfers an acetyl group.
Examples include:
* Histone acetyltransferases including CBP histone acetyltransferase
* Choline acetyltransferase
* Chloramphenicol acetyltran ...
. This acetylation affects
cell growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
,
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
, and
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
.
*Allosteric regulator
** Acetyl-CoA serves as an
allosteric regulator of
pyruvate dehydrogenase kinase (PDK). It regulates through the ratio of acetyl-CoA versus CoA. Increased concentration of acetyl-CoA activates PDK.
** Acetyl-CoA is also an allosteric activator of
pyruvate carboxylase.
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 a
WikiPathways''
See also
*
Malonyl-CoA decarboxylase
References
External links
*
{{DEFAULTSORT:Acetyl-Coa
Cholinergics
Metabolism
Thioesters of coenzyme A
Glycolysis