Genomes and Genes
Gene Symbol: Cpt1a
Description: carnitine palmitoyltransferase 1A
Alias: CPT-Ia, carnitine O-palmitoyltransferase 1, liver isoform, CPT I, CPT1-L, CPTI-L, Carnitine palmitoyltransferase 1 alpha, liver isoform, carnitine O-palmitoyltransferase I, liver isoform, carnitine palmitoyltransferase 1, liver, carnitine palmitoyltransferase 1a, liver
- Warfel J, Vandanmagsar B, Dubuisson O, Hodgeson S, Elks C, Ravussin E, et al. Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research. Am J Physiol Regul Integr Comp Physiol. 2017;312:R816-R820 pubmed publisher..i>Cpt1a is the predominate isoform in adipose tissue from all three species...
- Calderon Dominguez M, Sebastian D, Fucho R, Weber M, Mir J, García Casarrubios E, et al. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes. PLoS ONE. 2016;11:e0159399 pubmed publisher..Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection...
- Kolodziej M, Zammit V. Mature carnitine palmitoyltransferase I retains the N-terminus of the nascent protein in rat liver. FEBS Lett. 1993;327:294-6 pubmed..Knowledge of the identity of the N-terminus of the mature protein allows a reappraisal of the role of the two main. N-terminal hydrophobic domains of the protein and of the possible topology of the protein within the membrane. ..
- Gómez L, Heath S, Hagen T. Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart. Mech Ageing Dev. 2012;133:99-106 pubmed publisher..Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics. ..
- Sol E, Sargsyan E, Akusjarvi G, Bergsten P. Glucolipotoxicity in INS-1E cells is counteracted by carnitine palmitoyltransferase 1 over-expression. Biochem Biophys Res Commun. 2008;375:517-21 pubmed publisher..Also, apoptosis was alleviated and ER-stress markers p-eIF2alpha and CHOP were decreased in cells over-expressing CPT1. We conclude that regulated over-expression of CPT1 is beneficial for glucolipotoxic beta-cells. ..
- Jenei Z, Warren G, Hasan M, Zammit V, Dixon A. Packing of transmembrane domain 2 of carnitine palmitoyltransferase-1A affects oligomerization and malonyl-CoA sensitivity of the mitochondrial outer membrane protein. FASEB J. 2011;25:4522-30 pubmed publisher..TM2-mediated oligomerization is likely to be involved in the modulation of malonyl-CoA inhibition of CPT1A in response to short- and long-term changes in protein-protein and protein-lipid interactions that occur in vivo.
- Park E, Steffen M, Song S, Park V, Cook G. Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene. Biochem J. 1998;330 ( Pt 1):217-24 pubmed..The cDNAs of two isoforms of CPT I, termed the hepatic and muscle isoforms, have been cloned...
- Jenei Z, Borthwick K, Zammit V, Dixon A. Self-association of transmembrane domain 2 (TM2), but not TM1, in carnitine palmitoyltransferase 1A: role of GXXXG(A) motifs. J Biol Chem. 2009;284:6988-97 pubmed publisher..We have investigated the in vivo oligomerization of full-length rat CPT1A (rCPT1A) along with those of the N-terminal truncation/deletion mutants Delta(1-82), Delta(1-18), and Delta(19-30) ..
- Sebastian D, Guitart M, Garcia Martinez C, Mauvezin C, Orellana Gavaldà J, Serra D, et al. Novel role of FATP1 in mitochondrial fatty acid oxidation in skeletal muscle cells. J Lipid Res. 2009;50:1789-99 pubmed publisher..However, etomoxir, an irreversible inhibitor of CPT1, blocked all these effects. These data reveal that FATP1, like FAT/CD36, is associated with mitochondria and has a role in mitochondrial oxidation of fatty acids. ..
- de Vries Y, Arvidson D, Waterham H, Cregg J, Woldegiorgis G. Functional characterization of mitochondrial carnitine palmitoyltransferases I and II expressed in the yeast Pichia pastoris. Biochemistry. 1997;36:5285-92 pubmed..CPTI is thus reversibly inactivated by detergents. ..
- Morillas M, Gomez Puertas P, Bentebibel A, Sellés E, Casals N, Valencia A, et al. Identification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibition. J Biol Chem. 2003;278:9058-63 pubmed..we found 5 conserved amino acids (Thr(314), Asn(464), Ala(478), Met(593), and Cys(608), rat liver CPT I coordinates) common to inhibitable malonyl-CoA acyltransferases (carnitine octanoyltransferase and CPT I), and ..
- Borthwick K, Jackson V, Price N, Zammit V. The mitochondrial intermembrane loop region of rat carnitine palmitoyltransferase 1A is a major determinant of its malonyl-CoA sensitivity. J Biol Chem. 2006;281:32946-52 pubmed..The data suggest that the sequence spanning the loop-TM2 boundary determines the disposition of this TM in the membrane so as to alter the conformation of the C-terminal segment and thus affect its interaction with malonyl-CoA. ..
- Morillas M, López Viñas E, Valencia A, Serra D, Gomez Puertas P, Hegardt F, et al. Structural model of carnitine palmitoyltransferase I based on the carnitine acetyltransferase crystal. Biochem J. 2004;379:777-84 pubmedb>CPT I (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria...
- Broadway N, Pease R, Birdsey G, Shayeghi M, Turner N, David Saggerson E. The liver isoform of carnitine palmitoyltransferase 1 is not targeted to the endoplasmic reticulum. Biochem J. 2003;370:223-31 pubmed..It is concluded that L-CPT1 is not targeted to the ER membrane and that malonyl-CoA CAT in microsomal fractions is L-CPT1 that is derived from mitochondria, possibly from membrane contact sites. ..
- Rao J, Warren G, Estolt Povedano S, Zammit V, Ulmer T. An environment-dependent structural switch underlies the regulation of carnitine palmitoyltransferase 1A. J Biol Chem. 2011;286:42545-54 pubmed publisher..Here, we show that the N-terminal regulatory domain (N) of CPT1A can adopt two complex amphiphilic structural states, termed N? and N?, that interchange in a switch-like manner in ..
- Li P, Shan S, Chen Y, Ning Z, Sun S, Liu Q, et al. The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats. Br J Pharmacol. 2006;148:610-8 pubmed
- Zhang X, Wang C, Song G, Gan K, Kong D, Nie Q, et al. Mitofusion-2-mediated alleviation of insulin resistance in rats through reduction in lipid intermediate accumulation in skeletal muscle. J Biomed Sci. 2013;20:45 pubmed publisher..These observations contribute to the investigations of new diabetes therapies. ..
- Forcheron F, Abdallah P, Basset A, Del Carmine P, Haffar G, Beylot M. Nonalcoholic hepatic steatosis in Zucker diabetic rats: spontaneous evolution and effects of metformin and fenofibrate. Obesity (Silver Spring). 2009;17:1381-9 pubmed publisher..To conclude, metformin had only moderate effects on liver steatosis. The effects of fenofibrate was more marked but remained mild...
- Pan Y, Cohen I, Guillerault F, Feve B, Girard J, Prip Buus C. The extreme C terminus of rat liver carnitine palmitoyltransferase I is not involved in malonyl-CoA sensitivity but in initial protein folding. J Biol Chem. 2002;277:47184-9 pubmed
- Prip Buus C, Thuillier L, Abadi N, Prasad C, Dilling L, Klasing J, et al. Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community. Mol Genet Metab. 2001;73:46-54 pubmedHepatic carnitine palmitoyltransferase 1 (CPT1A) deficiency is a rare disorder of mitochondrial fatty acid oxidation inherited as an autosomal recessive trait...
- Cohen I, Guillerault F, Girard J, Prip Buus C. The N-terminal domain of rat liver carnitine palmitoyltransferase 1 contains an internal mitochondrial import signal and residues essential for folding of its C-terminal catalytic domain. J Biol Chem. 2001;276:5403-11 pubmed..Functional analysis of the deleted CPT1 proteins indicates that this folded C-terminal core, which may belong to the catalytic domain of CPT1, requires TM2 for its correct folding achievement and is in close proximity to residues 1-47. ..
- Fraser F, Corstorphine C, Zammit V. Topology of carnitine palmitoyltransferase I in the mitochondrial outer membrane. Biochem J. 1997;323 ( Pt 3):711-8 pubmedThe topology of carnitine palmitoyltransferase I (CPT I) in the outer membrane of rat liver mitochondria was studied using several approaches. 1...
- Faye A, Esnous C, Price N, Onfray M, Girard J, Prip Buus C. Rat liver carnitine palmitoyltransferase 1 forms an oligomeric complex within the outer mitochondrial membrane. J Biol Chem. 2007;282:26908-16 pubmed..Located within the outer mitochondrial membrane, CPT1A activity is inhibited by malonyl-CoA, its allosteric inhibitor...
- Napal L, Dai J, Treber M, Haro D, Marrero P, Woldegiorgis G. A single amino acid change (substitution of the conserved Glu-590 with alanine) in the C-terminal domain of rat liver carnitine palmitoyltransferase I increases its malonyl-CoA sensitivity close to that observed with the muscle isoform of the enzyme. J Biol Chem. 2003;278:34084-9 pubmed
- Lee K, Kerner J, Hoppel C. Mitochondrial carnitine palmitoyltransferase 1a (CPT1a) is part of an outer membrane fatty acid transfer complex. J Biol Chem. 2011;286:25655-62 pubmed publisherb>CPT1a (carnitine palmitoyltransferase 1a) in the liver mitochondrial outer membrane (MOM) catalyzes the primary regulated step in overall mitochondrial fatty acid oxidation...
- Bonfleur M, Borck P, Ribeiro R, Caetano L, Soares G, Carneiro E, et al. Improvement in the expression of hepatic genes involved in fatty acid metabolism in obese rats supplemented with taurine. Life Sci. 2015;135:15-21 pubmed publisher..Tau supplementation prevented obesity and hepatic TG deposition by upregulating MTP mRNA, ameliorating hepatic lipid efflux, and consequently enhancing PPAR-Î± which increases lipid oxidation through ACO and CPT-1a gene expressions. ..
- Zhang Y, Ma K, Song S, Elam M, Cook G, Park E. Peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) enhances the thyroid hormone induction of carnitine palmitoyltransferase I (CPT-I alpha). J Biol Chem. 2004;279:53963-71 pubmed..Our data demonstrate that PGC-1 alpha participates in the stimulation of CPT-I alpha gene expression by thyroid hormone and suggest that PGC-1 alpha is a coactivator for thyroid hormone. ..
- Sadana P, Zhang Y, Song S, Cook G, Elam M, Park E. Regulation of carnitine palmitoyltransferase I (CPT-Ialpha) gene expression by the peroxisome proliferator activated receptor gamma coactivator (PGC-1) isoforms. Mol Cell Endocrinol. 2007;267:6-16 pubmed..Overall, our results demonstrate that PGC-1beta is a coactivator in the T3 induction of CPT-Ialpha and that PGC-1beta has similarities and differences with the PGC-1alpha isoform. ..
- Gao S, Serra D, Keung W, Hegardt F, Lopaschuk G. Important role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake. Am J Physiol Endocrinol Metab. 2013;305:E336-47 pubmed publisher..VMN-selective modulation of CPT-1a activity may therefore be a promising strategy in controlling food intake and maintaining normal body weight. ..
- Nakamura S, Takamura T, Matsuzawa Nagata N, Takayama H, Misu H, Noda H, et al. Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biol Chem. 2009;284:14809-18 pubmed publisher..Thus, mitochondria-derived ROS induced by palmitate may be major contributors to JNK activation and cellular insulin resistance. ..
- Morillas M, Gomez Puertas P, Roca R, Serra D, Asins G, Valencia A, et al. Structural model of the catalytic core of carnitine palmitoyltransferase I and carnitine octanoyltransferase (COT): mutation of CPT I histidine 473 and alanine 381 and COT alanine 238 impairs the catalytic activity. J Biol Chem. 2001;276:45001-8 pubmedCarnitine palmitoyltransferase I (CPT I) and carnitine octanoyltransferase (COT) catalyze the conversion of long- and medium-chain acyl-CoA to acylcarnitines in the presence of carnitine...
- Lionetti L, Cavaliere G, Bergamo P, Trinchese G, De Filippo C, Gifuni G, et al. Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats. Mol Nutr Food Res. 2012;56:1596-600 pubmed publisher
- Ijlst L, Mandel H, Oostheim W, Ruiter J, Gutman A, Wanders R. Molecular basis of hepatic carnitine palmitoyltransferase I deficiency. J Clin Invest. 1998;102:527-31 pubmed..The effect of the identified mutation was investigated by heterologous expression in yeast. The expressed mutant CPT IA displayed only 2% of the activity of the expressed wild-type CPT IA, indicating that the D454G mutation is the ..
- Obici S, Feng Z, Arduini A, Conti R, Rossetti L. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med. 2003;9:756-61 pubmed
- Lewandowski E, Fischer S, Fasano M, Banke N, Walker L, Huqi A, et al. Acute liver carnitine palmitoyltransferase I overexpression recapitulates reduced palmitate oxidation of cardiac hypertrophy. Circ Res. 2013;112:57-65 pubmed publisher..The implications are that L-CPT1 expression induces metabolic remodeling hypertrophic signaling and that regulatory factors beyond malonyl CoA in the heart regulate long chain fatty acid oxidation via L-CPT1. ..
- Louet J, Hayhurst G, Gonzalez F, Girard J, Decaux J. The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). J Biol Chem. 2002;277:37991-8000 pubmedLiver carnitine palmitoyltransferase I catalyzes the transfer of long-chain fatty acids into mitochondria. L-CPT I is considered the rate-controlling enzyme in fatty acid oxidation...
- Serviddio G, Giudetti A, Bellanti F, Priore P, Rollo T, Tamborra R, et al. Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet. PLoS ONE. 2011;6:e24084 pubmed publisher..A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed. ..
- Dharancy S, Malapel M, Perlemuter G, Roskams T, Cheng Y, Dubuquoy L, et al. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Gastroenterology. 2005;128:334-42 pubmed..activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA)...
- Kerner J, Distler A, Minkler P, Parland W, Peterman S, Hoppel C. Phosphorylation of rat liver mitochondrial carnitine palmitoyltransferase-I: effect on the kinetic properties of the enzyme. J Biol Chem. 2004;279:41104-13 pubmed..These observations identify a new mechanism for regulation of hepatic CPT-I by phosphorylation. ..
- Louet J, Chatelain F, Decaux J, Park E, Kohl C, Pineau T, et al. Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor alpha (PPARalpha)-independent pathway. Biochem J. 2001;354:189-97 pubmedLiver carnitine palmitoyltransferase I (L-CPT I) catalyses the transfer of long-chain fatty acid (LCFA) for translocation across the mitochondrial membrane...
- Britton C, Schultz R, Zhang B, Esser V, Foster D, McGarry J. Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene. Proc Natl Acad Sci U S A. 1995;92:1984-8 pubmedUsing the cDNA for rat liver mitochondrial carnitine palmitoyltransferase I (CPT I; EC 18.104.22.168) as a probe, we isolated its counterpart as three overlapping clones from a human liver cDNA library...
- Ohashi K, Munetsuna E, Yamada H, Ando Y, Yamazaki M, Taromaru N, et al. High fructose consumption induces DNA methylation at PPARÎ± and CPT1A promoter regions in the rat liver. Biochem Biophys Res Commun. 2015;468:185-9 pubmed publisher..mRNA levels for peroxisome proliferator-activated receptor alpha (PPARÎ±) and carnitine palmitoyltransferase 1A (CPT1A) was analyzed using Real-time PCR...
- Rufer A, Thoma R, Hennig M. Structural insight into function and regulation of carnitine palmitoyltransferase. Cell Mol Life Sci. 2009;66:2489-501 pubmed publisher..However, a number of unresolved questions regarding the biochemistry and pharmacology of CPT enzymes remain and are addressed in this review. ..
- Hostetler H, Lupas D, Tan Y, Dai J, Kelzer M, Martin G, et al. Acyl-CoA binding proteins interact with the acyl-CoA binding domain of mitochondrial carnitine palmitoyl transferase I. Mol Cell Biochem. 2011;355:135-48 pubmed publisher..These data suggest that both interactions with lipid binding proteins and the peptide itself are important for optimal enzyme activity. ..
- Le May C, Caüzac M, Diradourian C, Perdereau D, Girard J, Burnol A, et al. Fatty acids induce L-CPT I gene expression through a PPARalpha-independent mechanism in rat hepatoma cells. J Nutr. 2005;135:2313-9 pubmed..In rat hepatocytes, we showed previously that L-CPT I gene expression was induced by LCFAs as well as by fibrates...
- Stefanovic Racic M, Perdomo G, Mantell B, Sipula I, Brown N, O Doherty R. A moderate increase in carnitine palmitoyltransferase 1a activity is sufficient to substantially reduce hepatic triglyceride levels. Am J Physiol Endocrinol Metab. 2008;294:E969-77 pubmed publisher..Therefore, interventions that increase CPT-1a activity could have potential benefits in the treatment of NAFLD. ..
- Moral R, Solanas M, Manzanares E, Haro D, Escrich E. Influence of DMBA-induced mammary cancer on the liver CPT I, mit HMG-CoA synthase and PPARalpha mRNA expression in rats fed a low or high corn oil diet. Int J Mol Med. 2004;14:283-7 pubmedHepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) enzymes play a key role in regulation of fatty acid oxidation and in ketogenic ..