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Acetyl-CoA

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Acetyl-CoA (acetyl coenzyme A) is a

molecule that participates in many
biochemical reactions in protein,
carbohydrate and lipid metabolism.[1] Its
main function is to deliver the acetyl group
to the citric acid cycle (Krebs cycle) to be
oxidized for energy production. Coenzyme
A (CoASH or CoA) consists of a β-
mercaptoethylamine group linked to the
vitamin pantothenic acid through an amide
linkage [2] 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 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).
 Acetyl-CoA

Names

IUPAC name
S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-
aminopurin-9-yl)-4-hydroxy-3-
phosphonooxyoxolan-2-yl]methoxy-
hydroxyphosphoryl]oxy-
hydroxyphosphoryl]oxy-2-hydroxy-3,3-
 dimethylbutanoyl]amino]propanoylamino]et
hyl] ethanethioate

Identifiers
CAS Number 72-89-9  

3D model (JSmol) Interactive image

Interactive image

ChEBI CHEBI:15351  

ChemSpider 392413  

ECHA InfoCard 100.000.719

IUPHAR/BPS 3038

KEGG C00024  

MeSH Acetyl+Coenzyme+A
PubChem CID 444493
InChI
InChI=1S/C23H38N7O17P3S/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17
(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,
32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38)/t13-,16-,17-,18+,22-/m1/s1 
Key: ZSLZBFCDCINBPY-ZSJPKINUSA-N 

InChI=1/C23H38N7O17P3S/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17
(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,
32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38)/t13-,16-,17-,18+,22-/m1/s1
Key: ZSLZBFCDCINBPY-ZSJPKINUBJ

SMILES
O=C(SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)[C@H](O)[C@@H]3O
P(=O)(O)O)C
CC(=O)SCCNC(=O)CCNC(=O)[C@@H](C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)n2cnc3c2ncnc3N)O)
OP(=O)(O)O)O

Properties
Chemical formula C23H38N7O17P3S

Molar mass 809.57 g·mol−1

Except where otherwise noted, data are given
for materials in their standard state (at 25 °C
[77 °F], 100 kPa).

 verify (what is   ?)

Infobox references
CoA is acetylated to acetyl-CoA by the
breakdown of carbohydrates through
glycolysis 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 and one
GTP per acetyl group.

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.

Direct synthesis
The acetylation of CoA is determined by
the carbon sources.[3][4]

Extramitochondrial …

At high glucose levels, glycolysis takes

place rapidly, thus increasing the
amount of citrate produced from the
tricarboxylic acid cycle. This citrate is
then exported to other organelles
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.[5][6]
At low glucose levels:
CoA is acetylated using acetate by
acetyl-CoA synthetase (ACS), also
coupled with ATP hydrolysis.[7]
Ethanol also serves as a carbon
source for acetylation of CoA
utilizing the enzyme alcohol
dehydrogenase.[8]
Degradation of branched-chain
ketogenic amino acids such as
valine, leucine, and isoleucine
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.[9]
Intramitochondrial …

Pyruvate dehydrogenase complex reaction

At high glucose levels, acetyl-CoA is

produced through glycolysis.[10]
Pyruvate 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. Other
conversions between pyruvate and
acetyl-CoA are possible. For example,
pyruvate formate lyase
disproportionates pyruvate into acetyl-
CoA and formic acid.

β-Oxidation of fatty acids

 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, 3-
hydroxyacyl-CoA dehydrogenase, and
thiolase. The cycle produces a new fatty
acid chain with two fewer carbons and
acetyl-CoA as a byproduct.[11]

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
Acetyl-CoA is produced by the
breakdown of both carbohydrates
(by glycolysis) and lipids (by β-
oxidation). It then enters the citric
acid cycle in the mitochondrion by
combining with oxaloacetate to
form citrate.[12][13]
Two acetyl-CoA molecules
condense to form acetoacetyl-CoA,
which gives rise to the formation of
acetoacetate and β-
hydroxybutyrate.[12] Acetoacetate,
β-hydroxybutyrate, and their
spontaneous breakdown product
acetone[14] are frequently, but
confusingly, known as ketone
bodies (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 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.[12] The occurrence
of high levels of ketone bodies in
the blood during starvation, a low-
carbohydrate diet, prolonged heavy
exercise, and uncontrolled type-1
diabetes mellitus is known as
ketosis, and in its extreme form in
out-of-control type-1 diabetes
mellitus, as ketoacidosis.
On the other hand, when the insulin
concentration in the blood is high,
and that of glucagon 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.[12] 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).[15] This cytosolic
acetyl-CoA can then be used to
synthesize fatty acids through
carboxylation by acetyl-CoA
carboxylase into malonyl CoA, the
first committed step in the
synthesis of fatty acids.[15][16] 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
phospholipids that make up the
bulk of the lipid bilayers of all
cellular membranes.[12]
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.
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.[12]
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.[12][16]
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.[17] In plants, these
include sesquiterpenes,
brassinosteroids (hormones), and
membrane sterols.
Steroid synthesis:
Acetyl-CoA participates in the
mevalonate pathway by partaking in
the synthesis of hydroxymethyl
glutaryl-CoA.
Acetylcholine synthesis:
 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 coenzyme A as
abyproduct.
Melatonin synthesis
Acetylation
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. This acetylation is
catalyzed by acetyltransferases.
This acetylation affects cell growth,
mitosis, and apoptosis.[18]
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.[19]
 Acetyl-CoA is also an allosteric
activator of pyruvate
carboxylase.[20]

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 .
 [File:

[
]]

TCA Cycle edit Statin Pathway edit

See also
Malonyl-CoA decarboxylase

References
1. "Acetyl CoA Crossroads" .
chemistry.elmhurst.edu. Retrieved
2016-11-08.
2. "Fatty Acids -- Structure of Acetyl
CoA" . library.med.utah.edu. Retrieved
2017-06-02.
3. Hynes, Michael J.; Murray, Sandra L.
(2010-07-01). "ATP-Citrate Lyase Is
Required for Production of Cytosolic
Acetyl Coenzyme A and Development
in Aspergillus nidulans" . Eukaryotic
Cell. 9 (7): 1039–1048.
doi:10.1128/EC.00080-10 . ISSN 1535-
 9778 . PMC 2901662 .
PMID 20495057 .
4. Wellen, Kathryn E.; Thompson, Craig B.
(2012-04-01). "A two-way street:
reciprocal regulation of metabolism
and signalling". Nature Reviews
Molecular Cell Biology. 13 (4): 270–
276. doi:10.1038/nrm3305 .
ISSN 1471-0072 . PMID 22395772 .
5. Storey, Kenneth B. (2005-02-25).
Functional Metabolism: Regulation
and Adaptation . John Wiley & Sons.
ISBN 9780471675570.
6. "ACLY ATP citrate lyase [Homo sapiens
(human)] - Gene - NCBI" .
www.ncbi.nlm.nih.gov. Retrieved
2016-11-06.
7. Ragsdale, S. W. (2004). "Life with
carbon monoxide". CRC Critical
Reviews in Biochemistry and
Molecular Biology. 39 (3): 165–195.
doi:10.1080/10409230490496577 .
PMID 15596550 .
8. Chatterjea (2004-01-01). Textbook of
Biochemistry for
Dental/Nursing/Pharmacy Students .
 Jaypee Brothers Publishers.
ISBN 9788180612046.
9. Berg, Jeremy M.; Tymoczko, John L.;
Stryer, Lubert (2002). Biochemistry
(5th ed.). W. H. Freeman. ISBN 978-
0716730514.
10. Blackstock, James C. (2014-06-28).
Guide to Biochemistry . Butterworth-
Heinemann. ISBN 9781483183671.
11. Houten, Sander Michel; Wanders,
Ronald J. A. (2010-03-02). "A general
introduction to the biochemistry of
mitochondrial fatty acid β-oxidation" .
Journal of Inherited Metabolic
 Disease. 33 (5): 469–477.
doi:10.1007/s10545-010-9061-2 .
ISSN 0141-8955 . PMC 2950079 .
PMID 20195903 .
12. Stryer, Lubert (1995). Biochemistry
(Fourth ed.). New York: W.H. Freeman
and Company. pp. 510–515, 559–565,
581–613, 614–623, 775–778.
ISBN 978-0-7167-2009-6.
13. "Oxidation of fatty acids" . 2013-10-11.
14. "Ketone body metabolism" . University
of Waterloo.
15. Ferre, P.; F. Foufelle (2007). "SREBP-1c
Transcription Factor and Lipid
 Homeostasis: Clinical Perspective".
Hormone Research. 68 (2): 72–82.
doi:10.1159/000100426 .
PMID 17344645 . "this process is
outlined graphically in page 73"
16. Voet, Donald; Judith G. Voet; Charlotte
W. Pratt (2006). Fundamentals of
Biochemistry, 2nd Edition . John Wiley
and Sons, Inc. pp. 547, 556 . ISBN 978-
0-471-21495-3.
17. Fatland, B. L. (2005). "Reverse Genetic
Characterization of Cytosolic Acetyl-
CoA Generation by ATP-Citrate Lyase
in Arabidopsis" . The Plant Cell Online.
 17 (1): 182–203.
doi:10.1105/tpc.104.026211 .
PMC 544498 . PMID 15608338 .
18. Yi, C. H.; Vakifahmetoglu-Norberg, H.;
Yuan, J. (2011-01-01). "Integration of
Apoptosis and Metabolism". Cold
Spring Harbor Symposia on
Quantitative Biology. 76: 375–387.
doi:10.1101/sqb.2011.76.010777 .
ISSN 0091-7451 . PMID 22089928 .
19. Pettit, Flora H.; Pelley, John W.; Reed,
Lester J. (1975-07-22). "Regulation of
pyruvate dehydrogenase kinase and
phosphatase by acetyl-CoA/CoA and
 NADH/NAD ratios". Biochemical and
Biophysical Research
Communications. 65 (2): 575–582.
doi:10.1016/S0006-291X(75)80185-9 .
PMID 167775 .
20. Jitrapakdee, Sarawut; Maurice, Martin
St.; Rayment, Ivan; Cleland, W. Wallace;
Wallace, John C.; Attwood, Paul V.
(2008-08-01). "Structure, Mechanism
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Carboxylase" . The Biochemical
Journal. 413 (3): 369–387.
doi:10.1042/BJ20080709 . ISSN 0264-
 6021 . PMC 2859305 .
PMID 18613815 .

External links
Acetyl+Coenzyme+A at the US National
Library of Medicine Medical Subject
Headings (MeSH)

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