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Information on EC 2.3.1.85 - fatty-acid synthase system and Organism(s) Mus musculus and UniProt Accession P19096

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EC Tree
     2 Transferases
         2.3 Acyltransferases
             2.3.1 Transferring groups other than aminoacyl groups
                2.3.1.85 fatty-acid synthase system
IUBMB Comments
The animal enzyme is a multi-functional protein catalysing the reactions of EC 2.3.1.38 [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase, EC 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I, EC 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase, EC 4.2.1.59 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 3.1.2.14 oleoyl-[acyl-carrier-protein] hydrolase. cf. EC 2.3.1.86, fatty-acyl-CoA synthase system.
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This record set is specific for:
Mus musculus
UNIPROT: P19096
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Word Map
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
hide
acetyl-CoA
+
7
malonyl-CoA
+
14
NADPH
+
14
H+
=
hexadecanoate
+
8
CoA
+
7
CO2
+
14
NADP+
+
6
H2O
+
7
+
14
+
14
=
+
8
+
7
+
14
+
6
Synonyms
fasii, fatty-acid synthase, fas-ii, type ii fatty acid synthase, yeast fatty acid synthase, fatty acid synthase ii, fatty acid synthase i, type 2 fatty acid synthase, fatty acid synthase type 2, f09e10.3 protein, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
fatty acid synthase
-
-
fatty-acid synthase
-
-
-
-
yeast fatty acid synthase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
-
redox reaction
-
-
-
-
Acyl group transfer
-
-
-
-
thioester hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester-hydrolysing)
The animal enzyme is a multi-functional protein catalysing the reactions of EC 2.3.1.38 [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase, EC 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I, EC 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase, EC 4.2.1.59 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 3.1.2.14 oleoyl-[acyl-carrier-protein] hydrolase. cf. EC 2.3.1.86, fatty-acyl-CoA synthase system.
CAS REGISTRY NUMBER
COMMENTARY hide
9045-77-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-hydroxybutanoyl-CoA + an [acyl-carrier protein]
CoA + 3-hydroxybutanoyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
3-methylbutanoyl-CoA + an [acyl-carrier protein]
CoA + 3-methylbutanoyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
acetoacetyl-CoA + an [acyl-carrier protein]
CoA + acetoacetyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
acetoacetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
show the reaction diagram
-
-
-
?
acetyl-CoA + an [acyl-carrier protein]
CoA + acetyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
show the reaction diagram
-
-
-
?
butanoyl-CoA + an [acyl-carrier protein]
CoA + butanoyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
butanoyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
show the reaction diagram
-
-
-
?
crotonyl-CoA + an [acyl-carrier protein]
CoA + crotonyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
malonyl-CoA + an [acyl-carrier protein]
CoA + a malonyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
methylmalonyl-CoA + an [acyl-carrier protein]
CoA + a methylmalonyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
octanoyl-CoA + an [acyl-carrier protein]
CoA + octanoyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
octanoyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
show the reaction diagram
-
-
-
?
palmitoyl-CoA + an [acyl-carrier protein]
CoA + palmitoyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
phenylacetyl-CoA + an [acyl-carrier protein]
CoA + phenylacetyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
succinyl-CoA + an [acyl-carrier protein]
CoA + succinyl-[acyl-carrier protein]
show the reaction diagram
-
-
-
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
show the reaction diagram
-
multifunctional enzyme, involved in animal fat synthesis
-
-
?
additional information
?
-
-
enzyme generated signals are needed to support preadipocyte differentiation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4'-phosphopantetheine
-
requirement, 1 mol associated with 1 mol subunit
NADPH
-
requirement, high specificity
additional information
-
no requirement for FMN
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-Dibromo-2-propanone
-
-
C75
-
0.05 mM, 90% reduction of enzyme activity, dramatic reduction of visible lipid droplet accumulation, reduction of enzyme mRNA
cerulenin
-
0.01 mM, 75% reduction of enzyme activity, dramatic reduction of visible lipid droplet accumulation, reduction of enzyme mRNA
diisopropylfluorophosphate
-
-
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
PMSF
-
-
pyridoxal 5'-phosphate
-
enoyl reductase activity, NADPH protects
triclosan
-
0.05 mM, 70% reduction of enzyme activity, dramatic reduction of visible lipid droplet accumulation, reduction of enzyme mRNA
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00172
3-hydroxybutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00206
3-methylbutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00086
acetoacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00163 - 0.003
acetyl-CoA
0.00164
butanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00136
crotonyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00128 - 0.018
malonyl-CoA
0.00062
methylmalonyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00073
octanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.0048
palmitoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00096
phenylacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.0021
succinyl-CoA
didomain construct, pH not specified in the publication, 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6.1
3-hydroxybutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
7.2
3-methylbutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
7.3
acetoacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
13 - 13.7
acetyl-CoA
10.8
butanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
6
crotonyl-CoA
didomain construct, pH not specified in the publication, 25°C
5 - 15.6
malonyl-CoA
4
methylmalonyl-CoA
didomain construct, pH not specified in the publication, 25°C
4.1
octanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
2.5
palmitoyl-CoA
didomain construct, pH not specified in the publication, 25°C
6
phenylacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
13.4
succinyl-CoA
didomain construct, pH not specified in the publication, 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8500
acetoacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
4000 - 8400
acetyl-CoA
6600
butanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
4400
crotonyl-CoA
didomain construct, pH not specified in the publication, 25°C
300 - 12200
malonyl-CoA
6500
methylmalonyl-CoA
didomain construct, pH not specified in the publication, 25°C
5600
octanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
500
palmitoyl-CoA
didomain construct, pH not specified in the publication, 25°C
6200
phenylacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
6400
succinyl-CoA
didomain construct, pH not specified in the publication, 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
transgenic adenocarcinoma of mouse prostate model, TRAMP
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
mice with fatty acid synthase knockout in the myocardium, FASKard, develop normally, manifest normal resting heart function, and have normal cardiac PPARalpha signaling as well as fatty acid oxidation. Mutant mice decompensate with stress. Most die within 1 h of transverse aortic constriction, probably due to arrhythmia. Voltage clamp measurements of FASKard cardiomyocytes show hyperactivation of L-type calcium channel current that can not be reversed with palmitate supplementation.Ca2+/calmodulin-dependent protein kinase II but not protein kinase A signaling is activated in FASKard hearts, and knockdown of fatty acid synthase in cultured cells activates Ca2+/calmodulin-dependent protein kinase II. In addition to being intolerant of the stress of acute pressure, FASKard hearts are also intolerant of the stress of aging, reflected as persistent CaMKII hyperactivation, progression to dilatation, and premature death by 1 year of age. Ca2+/calmodulin-dependent protein kinase II signaling appears to be pathogenic in FASKard hearts
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
FAS_MOUSE
2504
0
272428
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R606A
active site mutant of didomain construct. The specificity constant for malonyl-CoA is 40fold smaller than the wild-type constant
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dissociation of native enzyme leads to loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0°C, inactivation after 12 h, reactivation after 2 h at 25°C in the presence of NADPH, not acetyl-CoA or NADH
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
FAS expression is reduced by 25% in Ki-ras-induced actin-interacting protein-deficient liver
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
TRAMP mouse prostate adenocarcinoma cells show high enzyme expression and activity compared to nontransgenic littermates. Inhibition of enzyme expression and activity results in dose-dependent reduction in cell survival
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wakil, S.J.; Stoops, J.K.; Joshi, V.C.
Fatty acid synthesis and its regulation
Annu. Rev. Biochem.
52
537-579
1983
Anser sp., Bos taurus, Canis lupus familiaris, Gallus gallus, Columba sp., Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Yu, X.X.; Lewin, D.A.; Forrest, W.; Adams, S.H.
Cold elicits the simultaneous induction of fatty acid synthesis and beta-oxidation in murine brown adipose tissue: prediction from differential gene expression and confirmation in vivo
FASEB J.
16
155-168
2002
Mus musculus, Mus musculus FVB-N
Manually annotated by BRENDA team
Schmid, B.; Rippmann, J.F.; Tadayyon, M.; Hamilton, B.S.
Inhibition of fatty acid synthase prevents preadipocyte differentiation
Biochem. Biophys. Res. Commun.
328
1073-1082
2005
Mus musculus
Manually annotated by BRENDA team
Chirala, S.S.; Chang, H.; Matzuk, M.; Abu-Elheiga, L.; Mao, J.; Mahon, K.; Finegold, M.; Wakil, S.J.
Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero
Proc. Natl. Acad. Sci. USA
100
6358-6363
2003
Mus musculus
Manually annotated by BRENDA team
Pflug, B.R.; Pecher, S.M.; Brink, A.W.; Nelson, J.B.; Foster, B.A.
Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model
Prostate
57
245-254
2003
Mus musculus
Manually annotated by BRENDA team
Najjar, S.M.; Yang, Y.; Fernstroem, M.A.; Lee, S.J.; Deangelis, A.M.; Rjaily, G.A.; Al-Share, Q.Y.; Dai, T.; Miller, T.A.; Ratnam, S.; Ruch, R.J.; Smith, S.; Lin, S.H.; Beauchemin, N.; Oyarce, A.M.
Insulin acutely decreases hepatic fatty acid synthase activity
Cell Metab.
2
43-53
2005
Mus musculus
Manually annotated by BRENDA team
Matsukuma, K.E.; Bennett, M.K.; Huang, J.; Wang, L.; Gil, G.; Osborne, T.F.
Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase
J. Lipid Res.
47
2754-2761
2006
Mus musculus
Manually annotated by BRENDA team
Choi, J.S.; Kim, H.; Jung, M.H.; Hong, S.; Song, J.
Consumption of barley beta-glucan ameliorates fatty liver and insulin resistance in mice fed a high-fat diet
Mol. Nutr. Food Res.
54
1004-1013
2010
Mus musculus
Manually annotated by BRENDA team
Fujimoto, T.; Miyasaka, K.; Koyanagi, M.; Tsunoda, T.; Baba, I.; Doi, K.; Ohta, M.; Kato, N.; Sasazuki, T.; Shirasawa, S.
Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice
PLoS One
4
e4240
2009
Mus musculus
Manually annotated by BRENDA team
Razani, B.; Zhang, H.; Schulze, P.C.; Schilling, J.D.; Verbsky, J.; Lodhi, I.J.; Topkara, V.K.; Feng, C.; Coleman, T.; Kovacs, A.; Kelly, D.P.; Saffitz, J.E.; Dorn, G.W.; Nichols, C.G.; Semenkovich, C.F.
Fatty acid synthase modulates homeostatic responses to myocardial stress
J. Biol. Chem.
286
30949-30961
2011
Mus musculus
Manually annotated by BRENDA team
Rittner, A.; Paithankar, K.S.; Huu, K.V.; Grininger, M.
Characterization of the polyspecific transferase of murine type I fatty acid synthase (FAS) and implications for polyketide synthase (PKS) engineering
ACS Chem. Biol.
13
723-732
2018
Mus musculus (P19096)
Manually annotated by BRENDA team
Rittner, A.; Paithankar, K.S.; Drexler, D.J.; Himmler, A.; Grininger, M.
Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I
Protein Sci.
28
414-428
2019
Mus musculus (P19096)
Manually annotated by BRENDA team