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Gene Review

CPT1A  -  carnitine palmitoyltransferase 1A (liver)

Homo sapiens

Synonyms: CPT I, CPT1, CPT1-L, CPTI-L, Carnitine O-palmitoyltransferase 1, liver isoform, ...
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Disease relevance of CPT1A

  • A significant association between obesity phenotypes (BMI, weight, and waist girth) and CPT1B c.282-18C > T and p.E531K variants was observed (p < 0.05) No other association was found with variants in CPT1A and CPT1B [1].
  • L-CPT1 deficiency (13 families reported) presents as recurrent attacks of fasting hypoketotic hypoglycemia [2].
  • We conclude that hyperglycemia with hyperinsulinemia increases malonyl-CoA, inhibits functional CPT-1 activity, and shunts LCFA away from oxidation and toward storage in human muscle [3].
  • We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by increased malonyl coenzyme A (malonyl-CoA) (a known potent inhibitor of CPT-1) in human muscle during hyperglycemia with hyperinsulinemia [3].
  • In the present study we have identified and characterized the mutations underlying L-CPT I deficiency in six patients: five with classic symptoms of L-CPT I deficiency and one with symptoms that have not previously been associated with this disorder (muscle cramps and pain) [4].

Psychiatry related information on CPT1A

  • Inhibition of CPT1A activity normalized the hypothalamic levels of LCFA-CoAs and markedly inhibited feeding behavior and hepatic glucose fluxes in overfed rats [5].

High impact information on CPT1A

  • Fatty acid oxidation and ketogenesis are stimulated simultaneously with a paradoxical stimulation of fatty acid synthesis, which may be linked by virtue of a blunted response of mitochondrial carnitine palmitoyltransferase I (CPT-I) to malonyl coenzyme A (CoA) [6].
  • To this end, we targeted the liver isoform of carnitine palmitoyltransferase-1 (encoded by the CPT1A gene) by infusing either a sequence-specific ribozyme against CPT1A or an isoform-selective inhibitor of CPT1A activity in the third cerebral ventricle or in the mediobasal hypothalamus (MBH) [5].
  • In addition, a missense SNP in the carnitine palmitoyltransferase 1A (CPT1A) gene was associated with a decreased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 0.3 and 0.6, respectively) [7].
  • RESULTS: Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls [8].
  • PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA).The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid [8].

Chemical compound and disease context of CPT1A

  • BACKGROUND: Genistein increases CPT1A, a rate-limiting enzyme in the beta-oxidation pathway, enzyme activity by increasing CPT1A transcription in HepG2 cells and, consequently, suppresses high fat induced obesity in C57BL/6J mice [9].
  • The objective was to verify whether variants in the gene encoding the carnitine palmitoyltransferase I (CPT1), a key enzyme in beta-oxidation of fatty acids, are associated with obesity phenotypes, alone or in interaction with fat intake [1].

Biological context of CPT1A


Anatomical context of CPT1A


Associations of CPT1A with chemical compounds

  • While a major role for PPARalpha in the liver is to produce ketone bodies as fuel through beta-oxidation for peripheral tissues during fast, its participation in the control of CPT1A, the rate-limiting step of the pathway, remains controversial [10].
  • Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia [16].
  • In contrast, HepG2 cells seemed to be resistant to PPARalpha activation by 13-HPODE because no remarkable induction of the PPARalpha target genes ACO, CPT1A, mitochondrial HMG-CoA synthase and delta9-desaturase was observed [17].
  • We also show that tBid decreases CPT-1 activity by a mechanism independent of both malonyl-CoA, the key inhibitory molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease [18].
  • Natural mutation of Pro(479), which is also located in the malonyl-CoA predicted site, to Leu in a patient with human L-CPT I hereditary deficiency, modified malonyl-CoA sensitivity [19].

Regulatory relationships of CPT1A

  • Both glucagon and 3,3',5-tri-iodothyronine (T(3)) enhanced the transcription of the gene encoding L-CPT I, whereas insulin had the opposite effect [20].

Other interactions of CPT1A


Analytical, diagnostic and therapeutic context of CPT1A

  • Similar results were obtained with the CPT1A p.A275T variant as BMI and waist girth were higher in A275/A275 on a high fat compared to A275/A275 subjects on a low-fat diet [1].
  • Because CPT1A is involved in lipid metabolism and CPT1A deficiency in human is associated with the hypoketotic hypoglycemia disorder, the reduced CPT1A expression in hESC-NPCs raises a potential concern for the suitability of these cells in cell transplantation [25].
  • Consistently, DCM patients had a significantly higher cardiac CPT-1 mRNA expression (147+/-51% vs. control, p<0.05) compared to the control group [26].
  • In vivo inhibition of angiogenesis was determined by the disc angiogenesis system (DAS), where surgical sponge discs were placed subcutaneously in the rat dorsum and the ability of systemic treatment with liposomal CPT (LCPT), TPT, TNP-470 or cisplatin to inhibit vascular growth into the discs was evaluated [27].
  • Molecular cloning techniques have demonstrated that two CPT-I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes [28].


  1. Variants within the muscle and liver isoforms of the carnitine palmitoyltransferase I (CPT1) gene interact with fat intake to modulate indices of obesity in French-Canadians. Robitaille, J., Houde, A., Lemieux, S., Pérusse, L., Gaudet, D., Vohl, M.C. J. Mol. Med. (2007) [Pubmed]
  2. Carnitine palmitoyltransferase deficiencies. Bonnefont, J.P., Demaugre, F., Prip-Buus, C., Saudubray, J.M., Brivet, M., Abadi, N., Thuillier, L. Mol. Genet. Metab. (1999) [Pubmed]
  3. Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle. Rasmussen, B.B., Holmbäck, U.C., Volpi, E., Morio-Liondore, B., Paddon-Jones, D., Wolfe, R.R. J. Clin. Invest. (2002) [Pubmed]
  4. Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme. Brown, N.F., Mullur, R.S., Subramanian, I., Esser, V., Bennett, M.J., Saudubray, J.M., Feigenbaum, A.S., Kobari, J.A., Macleod, P.M., McGarry, J.D., Cohen, J.C. J. Lipid Res. (2001) [Pubmed]
  5. Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats. Pocai, A., Lam, T.K., Obici, S., Gutierrez-Juarez, R., Muse, E.D., Arduini, A., Rossetti, L. J. Clin. Invest. (2006) [Pubmed]
  6. Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states. Heimberg, M., Olubadewo, J.O., Wilcox, H.G. Endocr. Rev. (1985) [Pubmed]
  7. Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C. Huang, H., Shiffman, M.L., Cheung, R.C., Layden, T.J., Friedman, S., Abar, O.T., Yee, L., Chokkalingam, A.P., Schrodi, S.J., Chan, J., Catanese, J.J., Leong, D.U., Ross, D., Hu, X., Monto, A., McAllister, L.B., Broder, S., White, T., Sninsky, J.J., Wright, T.L. Gastroenterology (2006) [Pubmed]
  8. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Dharancy, S., Malapel, M., Perlemuter, G., Roskams, T., Cheng, Y., Dubuquoy, L., Podevin, P., Conti, F., Canva, V., Philippe, D., Gambiez, L., Mathurin, P., Paris, J.C., Schoonjans, K., Calmus, Y., Pol, S., Auwerx, J., Desreumaux, P. Gastroenterology (2005) [Pubmed]
  9. Positive regulation of hepatic carnitine palmitoyl transferase 1A (CPT1A) activities by soy isoflavones and L-carnitine. Shin, E.S., Cho, S.Y., Lee, E.H., Lee, S.J., Chang, I.S., Lee, T.R. European journal of nutrition. (2006) [Pubmed]
  10. An intronic peroxisome proliferator-activated receptor-binding sequence mediates fatty acid induction of the human carnitine palmitoyltransferase 1A. Napal, L., Marrero, P.F., Haro, D. J. Mol. Biol. (2005) [Pubmed]
  11. Cloning and expression of the liver and muscle isoforms of ovine carnitine palmitoyltransferase 1: residues within the N-terminus of the muscle isoform influence the kinetic properties of the enzyme. Price, N.T., Jackson, V.N., van der Leij, F.R., Cameron, J.M., Travers, M.T., Bartelds, B., Huijkman, N.C., Zammit, V.A. Biochem. J. (2003) [Pubmed]
  12. Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B). Britton, C.H., Mackey, D.W., Esser, V., Foster, D.W., Burns, D.K., Yarnall, D.P., Froguel, P., McGarry, J.D. Genomics (1997) [Pubmed]
  13. Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community. Prip-Buus, C., Thuillier, L., Abadi, N., Prasad, C., Dilling, L., Klasing, J., Demaugre, F., Greenberg, C.R., Haworth, J.C., Droin, V., Kadhom, N., Gobin, S., Kamoun, P., Girard, J., Bonnefont, J.P. Mol. Genet. Metab. (2001) [Pubmed]
  14. Structure and function of carnitine acyltransferases. Jogl, G., Hsiao, Y.S., Tong, L. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  15. Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation. Inter-tissue and inter-species expression of CPT I and CPT II enzymes. Brown, N.F., Hill, J.K., Esser, V., Kirkland, J.L., Corkey, B.E., Foster, D.W., McGarry, J.D. Biochem. J. (1997) [Pubmed]
  16. Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia. Gobin, S., Bonnefont, J.P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W.L., Green, A., Gray, G., Girard, J., Thuillier, L. Hum. Genet. (2002) [Pubmed]
  17. Differential action of 13-HPODE on PPARalpha downstream genes in rat Fao and human HepG2 hepatoma cell lines. König, B., Eder, K. J. Nutr. Biochem. (2006) [Pubmed]
  18. tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1. Giordano, A., Calvani, M., Petillo, O., Grippo, P., Tuccillo, F., Melone, M.A., Bonelli, P., Calarco, A., Peluso, G. Cell Death Differ. (2005) [Pubmed]
  19. Structural model of a malonyl-CoA-binding site of carnitine octanoyltransferase and carnitine palmitoyltransferase I: mutational analysis of a malonyl-CoA affinity domain. Morillas, M., Gómez-Puertas, P., Rubí, B., Clotet, J., Ariño, J., Valencia, A., Hegardt, F.G., Serra, D., Asins, G. J. Biol. Chem. (2002) [Pubmed]
  20. Regulation of liver carnitine palmitoyltransferase I gene expression by hormones and fatty acids. Louet, J.F., Le May, C., Pégorier, J.P., Decaux, J.F., Girard, J. Biochem. Soc. Trans. (2001) [Pubmed]
  21. Genomics of the human carnitine acyltransferase genes. van der Leij, F.R., Huijkman, N.C., Boomsma, C., Kuipers, J.R., Bartelds, B. Mol. Genet. Metab. (2000) [Pubmed]
  22. Effects of doxorubicin-containing chemotherapy and a combination with L-carnitine on oxidative metabolism in patients with non-Hodgkin lymphoma. Waldner, R., Laschan, C., Lohninger, A., Gessner, M., Tüchler, H., Huemer, M., Spiegel, W., Karlic, H. J. Cancer Res. Clin. Oncol. (2006) [Pubmed]
  23. Differential effects of peroxisome proliferator-activated receptor activators on the mRNA levels of genes involved in lipid metabolism in primary human monocyte-derived macrophages. Cabrero, A., Cubero, M., Llaverías, G., Jové, M., Planavila, A., Alegret, M., Sánchez, R., Laguna, J.C., Carrera, M.V. Metab. Clin. Exp. (2003) [Pubmed]
  24. Genistein enhances expression of genes involved in fatty acid catabolism through activation of PPARalpha. Kim, S., Shin, H.J., Kim, S.Y., Kim, J.H., Lee, Y.S., Kim, D.H., Lee, M.O. Mol. Cell. Endocrinol. (2004) [Pubmed]
  25. Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells. Shen, Y., Chow, J., Wang, Z., Fan, G. Hum. Mol. Genet. (2006) [Pubmed]
  26. Cardiac PPARalpha expression in patients with dilated cardiomyopathy. Schupp, M., Kintscher, U., Fielitz, J., Thomas, J., Pregla, R., Hetzer, R., Unger, T., Regitz-Zagrosek, V. Eur. J. Heart Fail. (2006) [Pubmed]
  27. Antiangiogenic potential of camptothecin and topotecan. Clements, M.K., Jones, C.B., Cumming, M., Daoud, S.S. Cancer Chemother. Pharmacol. (1999) [Pubmed]
  28. Differential regulation in the heart of mitochondrial carnitine palmitoyltransferase-I muscle and liver isoforms. Park, E.A., Cook, G.A. Mol. Cell. Biochem. (1998) [Pubmed]
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