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Gene Review

CHPT1  -  choline phosphotransferase 1

Homo sapiens

Synonyms: AAPT1-like protein, CPT, CPT1, Cholinephosphotransferase 1, Diacylglycerol cholinephosphotransferase 1, ...
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Disease relevance of CHPT1

  • We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F) [1].
  • The dual action of the C75 class of compounds as fatty acid synthase inhibitors and CPT-1 agonists has therapeutic implications in the treatment of obesity and type II diabetes [2].
  • Irinotecan dosing: does the CPT in CPT-11 stand for "Can't Predict Toxicity" [3]?
  • CPT-11-resistant cells (PC-7/CPT) established from a human non-small cell lung cancer cell (PC-7) by stepwise, continuous treatment with CPT-11 exhibit about a 10-fold increase in resistance to the drug [4].
  • Competitive inhibition of choline phosphotransferase by geranylgeraniol and farnesol inhibits phosphatidylcholine synthesis and induces apoptosis in human lung adenocarcinoma A549 cells [5].

Psychiatry related information on CHPT1

  • CPT: a cure for fiscal agnosia [6].
  • Compared to placebo, active nicotine spray significantly decreased reaction time on the Conner's CPT and improved scores on a measure purported to reflect spatial working memory on a dot task [7].
  • Subjects were presented with a cued version of the continuous performance task (CPT; ABX) [8].
  • No significant differences were observed on any of the clinical neuropsychological tests, or in the number of false positive (FP) or non-responses to stimuli (NR) from the CPT [9].
  • Commentary. Health and behavior CPT codes: an opportunity to revolutionize reimbursement in pediatric psychology [10].

High impact information on CHPT1

  • One exception is carnitine palmitoyltransferase I (CPT I) deficiency, of which until now no mutations have been reported although the defect is enzymatically well characterized [11].
  • Furthermore, in patient's fibroblasts the CPT IA protein was markedly reduced on immunoblot, suggesting that the mutation renders the protein unstable [11].
  • Here we report the first delineation of the molecular basis of hepatic CPT I deficiency in a new case. cDNA analysis revealed that this patient was homozygous for a missense mutation (D454G) [11].
  • CONCLUSIONS: Kinetics of the reversal of drug-induced SSB in isolated nuclei suggest that dissociation of SN-38 from cleavable complexes is much slower than that of CPT [12].
  • IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11 [12].

Chemical compound and disease context of CHPT1


Biological context of CHPT1

  • The hCPT1 and human choline/ethanolaminephosphotransferase (hCEPT1) predicted amino acid sequences possessed 60% overall identity and had only one variation in the amino acid residues within the CDP-alcohol phosphotransferase catalytic motif [18].
  • Differences in DNA sequence selectivity and the stability of cleavable complexes induced by the drugs may also contribute to differences among CPT derivatives [12].
  • In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C1000), values were 0.037 microM for SN-38, 0.051 microM for CPT, 0.085 microM for 9-AC, 0.28 microM for TPT, and greater than 1 microM for CPT-11 [12].
  • The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPT caused an increase in mean arterial pressure and heart rate [19].
  • Etomoxir, an inhibitor of carnitine O-palmitoyltransferase-1 (CPT-1), reversed the increased energy expenditure in DIO mice by inhibiting fatty acid oxidation [2].

Anatomical context of CHPT1


Associations of CHPT1 with chemical compounds

  • In vitro assessment of hCPT1 and hCEPT1 derived cholinephosphotransferase activities also revealed differences in diradylglycerol specificities including their capacity to synthesize platelet-activating factor and platelet-activating factor precursor [18].
  • Cholinephosphotransferase (CPT), the terminal enzyme in the de novo synthesis of PC, has an important role in regulating the acyl group of PC in mammalian cells [21].
  • Of these, three are null mutations, but the third one shows an interesting serine to tyrosine substitution (at amino acid position 89 of our partial sequence which corresponds to position 323 of the CPT sequence reported as NM_020244 in GenBank) in 11-9-14 cells [21].
  • The potency ranking was the same as in whole cells, and the C1000 values were 0.0025 microM for SN-38, 0.012 microM for CPT, 0.021 microM for 9-AC, 0.44 microM for TPT, and greater than 0.1 microM for CPT-11 [12].
  • Studies in human cancer cells showed that C75 competed with malonyl-CoA, as measured by CPT-1 activity assays [2].

Other interactions of CHPT1


Analytical, diagnostic and therapeutic context of CHPT1

  • CPT and exercise caused slight constriction (-3.5 +/- 4.5% and -2.7 +/- 10.5%, respectively; both P < .001 versus control subjects) [24].
  • Additional experiments established that liver and fibroblasts express the same isoform of mitochondrial CPT I, legitimizing the use of fibroblast assays in the differential diagnosis of the "muscle" and "hepatic" forms of CPT deficiency [25].
  • TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling) assays demonstrate that gammaH2AX formation in late S and G2 cells following CPT treatment corresponds to DNA breaks [26].
  • Extensive sequence analysis was subsequently performed on 14 samples which either had a CPT2 mutation detected by ASO screening or the residual CPT activity was below that observed in ASO positive samples [27].
  • The regional cerebral metabolic rates of 19 male medication-withdrawn schizophrenic patients were determined by positron emission tomography (PET) while performing an auditory discrimination task (CPT) [28].


  1. Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist. Akech, J., Roy, S.S., Das, S.K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  2. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Thupari, J.N., Landree, L.E., Ronnett, G.V., Kuhajda, F.P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Irinotecan dosing: does the CPT in CPT-11 stand for "Can't Predict Toxicity"? Ratain, M.J. J. Clin. Oncol. (2002) [Pubmed]
  4. Establishment of a camptothecin analogue (CPT-11)-resistant cell line of human non-small cell lung cancer: characterization and mechanism of resistance. Kanzawa, F., Sugimoto, Y., Minato, K., Kasahara, K., Bungo, M., Nakagawa, K., Fujiwara, Y., Liu, L.F., Saijo, N. Cancer Res. (1990) [Pubmed]
  5. Competitive inhibition of choline phosphotransferase by geranylgeraniol and farnesol inhibits phosphatidylcholine synthesis and induces apoptosis in human lung adenocarcinoma A549 cells. Miquel, K., Pradines, A., Tercé, F., Selmi, S., Favre, G. J. Biol. Chem. (1998) [Pubmed]
  6. CPT: a cure for fiscal agnosia. Rosenbaum, H.E., Segerson, J. Neurology (1979) [Pubmed]
  7. Effects of nicotine nasal spray on cognitive function in schizophrenia. Smith, R.C., Warner-Cohen, J., Matute, M., Butler, E., Kelly, E., Vaidhyanathaswamy, S., Khan, A. Neuropsychopharmacology (2006) [Pubmed]
  8. Source analysis of the N2 in a cued Go/NoGo task. Bekker, E.M., Kenemans, J.L., Verbaten, M.N. Brain research. Cognitive brain research. (2005) [Pubmed]
  9. Slowed reaction time in asymptomatic HIV-positive patients. Karlsen, N.R., Reinvang, I., Frøland, S.S. Acta neurologica Scandinavica. (1992) [Pubmed]
  10. Commentary. Health and behavior CPT codes: an opportunity to revolutionize reimbursement in pediatric psychology. Noll, R.B., Fischer, S. Journal of pediatric psychology. (2004) [Pubmed]
  11. Molecular basis of hepatic carnitine palmitoyltransferase I deficiency. IJlst, L., Mandel, H., Oostheim, W., Ruiter, J.P., Gutman, A., Wanders, R.J. J. Clin. Invest. (1998) [Pubmed]
  12. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. Tanizawa, A., Fujimori, A., Fujimori, Y., Pommier, Y. J. Natl. Cancer Inst. (1994) [Pubmed]
  13. Role of malonyl-CoA in heart disease and the hypothalamic control of obesity. Folmes, C.D., Lopaschuk, G.D. Cardiovasc. Res. (2007) [Pubmed]
  14. Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent antiinflammatory compound in vivo. Sancho, R., Lucena, C., Macho, A., Calzado, M.A., Blanco-Molina, M., Minassi, A., Appendino, G., Muñoz, E. Eur. J. Immunol. (2002) [Pubmed]
  15. Guanfacine treatment of cognitive impairment in schizophrenia. Friedman, J.I., Adler, D.N., Temporini, H.D., Kemether, E., Harvey, P.D., White, L., Parrella, M., Davis, K.L. Neuropsychopharmacology (2001) [Pubmed]
  16. Coimmunoprecipitation of FAT/CD36 and CPT I in skeletal muscle increases proportionally with fat oxidation after endurance exercise training. Schenk, S., Horowitz, J.F. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  17. Lipid oxidation is reduced in obese human skeletal muscle. Kim, J.Y., Hickner, R.C., Cortright, R.L., Dohm, G.L., Houmard, J.A. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  18. Cloning, genomic organization, and characterization of a human cholinephosphotransferase. Henneberry, A.L., Wistow, G., McMaster, C.R. J. Biol. Chem. (2000) [Pubmed]
  19. ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Perondi, R., Saino, A., Tio, R.A., Pomidossi, G., Gregorini, L., Alessio, P., Morganti, A., Zanchetti, A., Mancia, G. Circulation (1992) [Pubmed]
  20. Selective accumulation of cytosol CDP-choline as an isolated erythrocyte defect in chronic hemolysis. Paglia, D.E., Valentine, W.N., Nakatani, M., Rauth, B.J. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  21. Differential expression of cholinephosphotransferase in normal and cancerous human mammary epithelial cells. Ghosh, A., Akech, J., Mukherjee, S., Das, S.K. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  22. Phospholipid-metabolizing enzymes in Alzheimer's disease: increased lysophospholipid acyltransferase activity and decreased phospholipase A2 activity. Ross, B.M., Moszczynska, A., Erlich, J., Kish, S.J. J. Neurochem. (1998) [Pubmed]
  23. Signal transduction in vascular smooth muscle: diacylglycerol second messengers and PKC action. Lee, M.W., Severson, D.L. Am. J. Physiol. (1994) [Pubmed]
  24. Sympathetic stimulation overrides flow-mediated endothelium-dependent epicardial coronary vasodilation in transplant patients. Aptecar, E., Dupouy, P., Benvenuti, C., Mazzucotelli, J.P., Teiger, E., Geschwind, H., Castaigne, A., Loisance, D., Dubois-Rande, J.L. Circulation (1996) [Pubmed]
  25. Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene. Britton, C.H., Schultz, R.A., Zhang, B., Esser, V., Foster, D.W., McGarry, J.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  26. p21CDKN1A allows the repair of replication-mediated DNA double-strand breaks induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor 7-hydroxystaurosporine. Furuta, T., Hayward, R.L., Meng, L.H., Takemura, H., Aune, G.J., Bonner, W.M., Aladjem, M.I., Kohn, K.W., Pommier, Y. Oncogene (2006) [Pubmed]
  27. Novel mutations associated with carnitine palmitoyltransferase II deficiency. Taggart, R.T., Smail, D., Apolito, C., Vladutiu, G.D. Hum. Mutat. (1999) [Pubmed]
  28. Abnormalities in the distributed network of sustained attention predict neuroleptic treatment response in schizophrenia. Cohen, R.M., Nordahl, T.E., Semple, W.E., Andreason, P., Pickar, D. Neuropsychopharmacology (1998) [Pubmed]
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