Acyl-CoA:lysocardiolipin acyltransferase-1

Acyl-CoA:lysocardiolipin acyltransferase-1
Identifiers
Symbol	ALCAT1
Alt. symbols	LCLAT1, LYCAT
NCBI gene	253558
HGNC	26756
OMIM	614241
RefSeq	NM_182551.3
UniProt	Q6UWP7
Other data
Locus	Chr. 2 p23.1

Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1) is a polyglycerophospholipid acyltransferase of the endoplasmic reticulum which is primarily known for catalyzing the acylation of monolysocardiolipin back into cardiolipin, although it does catalyze the acylation of other polyglycerophospholipids.[1]

ALCAT1 is widely distributed throughout the body, with the highest concentrations being in the heart and liver.[2]

Function

ALCAT1 facilitates the transfer of acyl groups from linoleoyl-CoA and oleoyl-CoA onto monolysocardiolipin and dilysocardiolipin. The pathway is thought to be important in maintaining heart function, as the ALCAT1 gene is conserved among many species of vertebrates, but not in organisms lacking heart atria.[2]

Recent research has shown that ALCAT1 activity is involved with mitochondrial dysfunction in disease. ALCAT1 is upregulated by oxidative stress and diet-induced obesity, and produces a species of cardiolipin that is highly sensitive to oxidative damage. Deficiency of ALCAT1 prevented the onset of diet-induced obesity, improved mitochondria function, and prevented insulin resistance.[3]

Interactions

ALCAT1 was reported to be regulated by thyroid hormone, a universal regulator of metabolism. Its activity also appeared to be inhibited by the presence of ADP and ATP, but not its analogs or other nucleotides, such as UTP and GTP.[1]

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References

Cao J, Shen W, Chang Z, Shi Y (April 2009). "ALCAT1 is a polyglycerophospholipid acyltransferase potently regulated by adenine nucleotide and thyroid status". American Journal of Physiology. Endocrinology and Metabolism. 296 (4): E647-53. doi:10.1152/ajpendo.90761.2008. PMC 3734525. PMID 19106248.
Cao J, Liu Y, Lockwood J, Burn P, Shi Y (July 2004). "A novel cardiolipin-remodeling pathway revealed by a gene encoding an endoplasmic reticulum-associated acyl-CoA:lysocardiolipin acyltransferase (ALCAT1) in mouse". The Journal of Biological Chemistry. 279 (30): 31727–34. doi:10.1074/jbc.M402930200. PMID 15152008.
Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y (August 2010). "Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity". Cell Metabolism. 12 (2): 154–65. doi:10.1016/j.cmet.2010.07.003. PMC 2923392. PMID 20674860.

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[CaoShen2008-1] Cao J, Shen W, Chang Z, Shi Y (April 2009). "ALCAT1 is a polyglycerophospholipid acyltransferase potently regulated by adenine nucleotide and thyroid status". American Journal of Physiology. Endocrinology and Metabolism. 296 (4): E647-53. doi:10.1152/ajpendo.90761.2008. PMC 3734525. PMID 19106248.

[Cao2004-2] Cao J, Liu Y, Lockwood J, Burn P, Shi Y (July 2004). "A novel cardiolipin-remodeling pathway revealed by a gene encoding an endoplasmic reticulum-associated acyl-CoA:lysocardiolipin acyltransferase (ALCAT1) in mouse". The Journal of Biological Chemistry. 279 (30): 31727–34. doi:10.1074/jbc.M402930200. PMID 15152008.

[LiRomestaing2010-3] Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y (August 2010). "Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity". Cell Metabolism. 12 (2): 154–65. doi:10.1016/j.cmet.2010.07.003. PMC 2923392. PMID 20674860.

Transferases: acyltransferases (EC 2.3)
2.3.1: other than amino-acyl groups	acetyltransferases: Acetyl-Coenzyme A acetyltransferase N-Acetylglutamate synthase Choline acetyltransferase Dihydrolipoyl transacetylase Acetyl-CoA C-acyltransferase Beta-galactoside transacetylase Chloramphenicol acetyltransferase N-acetyltransferase Serotonin N-acetyl transferase HGSNAT ARD1A Histone acetyltransferase P300/CBP NAT2 palmitoyltransferases: Carnitine O-palmitoyltransferase CPT1 CPT2 Serine C-palmitoyltransferase SPTLC1 SPTLC2 other: Acyltransferase like 2 Aminolevulinic acid synthase Beta-ketoacyl-ACP synthase Glyceronephosphate O-acyltransferase Lecithin—cholesterol acyltransferase Glycerol-3-phosphate O-acyltransferase 1-acylglycerol-3-phosphate O-acyltransferase 2-acylglycerol-3-phosphate O-acyltransferase ABHD5
2.3.2: Aminoacyltransferases	Gamma-glutamyl transpeptidase Peptidyl transferase Transglutaminase Tissue transglutaminase Keratinocyte transglutaminase Factor XIII
2.3.3: converted into alkyl on transfer	Citrate synthase Decylcitrate synthase Citrate (Re)-synthase Decylhomocitrate synthase 2-methylcitrate synthase 2-ethylmalate synthase 3-ethylmalate synthase ATP citrate lyase Malate synthase HMG-CoA synthase HMGCS2 2-hydroxyglutarate synthase 3-propylmalate synthase 2-isopropylmalate synthase Homocitrate synthase Sulfoacetaldehyde acetyltransferase

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)