Carnitine precursor γ-butyrobetaine is a novel substrate of the Na+- and C1--dependent GABA transporter Gat2

Drug Metabolism and Pharmacokinetics

Volumn 26, Issue 6, 2011, Pages 632-636

  Nakanishi, Takeo ^a   Fukuyama, Yoko ^a   Fujita, Masaharu ^a   Shirasaka, Yoshiyuki ^a   Tamai, Ikumi ^a  

^a KANAZAWA UNIVERSITY   (Japan)

Author keywords

Carnitine; GABA; GAT2; Juvenile visceral steatosis(Jvs); OCTN2; Transporter; butyrobetaine

Indexed keywords

4 AMINOBUTYRIC ACID CARRIER 2; CARRIER PROTEIN; CHLORIDE ION; GAMMA BUTYROBETAINE; MESSENGER RNA; ORGANIC CATION TRANSPORTER 2; SODIUM ION; UNCLASSIFIED DRUG;

AMINO ACID TRANSPORT; ANIMAL CELL; ANIMAL TISSUE; BRAIN; CONTROLLED STUDY; KIDNEY; LIVER; MOUSE; NONHUMAN; NOTE; OOCYTE; PROTEIN EXPRESSION; TISSUE SPECIFICITY; TRANSPORT KINETICS; XENOPUS LAEVIS;

EID: 84855209786     PISSN: 13474367     EISSN: 18800920     Source Type: Journal    
DOI: 10.2133/dmpk.DMPK-11-NT-053     Document Type: Note

References (19)

1. McGarry, J. D. and Brown, N. F.: The mitochondrial carnitine palmitoyltransferase system: from concept to molecular analysis. Eur. J. Biochem., 244: 1-14 1997.
2. Ramsay, R. R., Gandour, R. D. and van der Leij, F. R.: Molecular enzymology of carnitine transfer and transport. Biochim. Biophys. Acta, 1546: 21-43 2001.
3. Tanphaichitr, V. and Broquist, H. P.: Role of lysine and {Thorn}-N-trimethyllysine in carnitine biosynthesis. II. Studies in the rat. J. Biol. Chem., 248: 2176-2181 1973.
4. Nezu, J.-i., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., Takada, G., Matsuishi, T., Yoshino, M., Kato, H., Ohura, T., Tsujimoto, G., Hayakawa, J.-i., Shimane, M. and Tsuji, A.: Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat. Genet., 21: 91-94 1999.
5. 0,+ from mouse colon expressed in HRPE cells and Xenopus oocytes. J. Physiol., 532: 297-304 (2001).
6. Enomoto, A., Wempe, M. F., Tsuchida, H., Shin, H. J., Cha, S. H., Anzai, N., Goto, A., Sakamoto, A., Niwa, T., Kanai, Y., Anders, M. W. and Endou, H.: Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition. J. Biol. Chem., 277: 36262-36271 (2002).
7. Vaz, F. M. and Wanders, R. J. A.: Carnitine biosynthesis in mammals. Biochem. J., 361: 417-429 (2002).
8. Tamai, I., Ohashi, R., Nezu, J.-i., Sai, Y., Kobayashi, D., Oku, A., Shimane, M. and Tsuji, A.: Molecular and functional characterization of organic cation/carnitine transporter family in mice. J. Biol. Chem., 275: 40064-40072 (2000).
9. Fujita, M., Nakanishi, T., Shibue, Y., Kobayashi, D., Moseley, R. H., Shirasaka, Y. and Tamai, I.: Hepatic uptake of È-butyrobetaine, a precursor of carnitine biosynthesis, in rats. Am. J. Physiol. Gastrointest. Liver Physiol., 297: G681-G686 (2009).
10. Nakanishi, T., Doyle, L. A., Hassel, B., Wei, Y., Bauer, K. S., Wu, S., Pumplin, D. W., Fang, H.-B. and Ross, D. D.: Functional characterization of human breast cancer resistance protein BCRP, ABCG2¥ expressed in the oocytes of Xenopus laevis. Mol. Pharmacol., 64: 1452-1462 (2003).
11. Nakanishi, T., Haruta, T., Shirasaka, Y. and Tamai, I.: Organic cation transporter-mediated renal secretion of ipratropium and tiotropium in rats and humans. Drug Metab. Dispos., 39: 117-122 (2011).
12. Livak, K. J. and Schmittgen, T. D.: Analysis of relative gene expression data using real-time quantitative PCR and the 2- adelta«adelta«CT method. Methods, 25: 402-408 (2001).
13. Higashi, Y., Yokogawa, K., Takeuchi, N., Tamai, I., Nomura, M., Hashimoto, N., Hayakawa, J. I., Miyamoto, K. I. and Tsuji, A.: Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice. J. Pharm. Pharmacol., 53: 527-533 (2001).
14. Borden, L. A., Smith, K. E., Hartig, P. R., Branchek, T. A. and Weinshank, R. L.: Molecular heterogeneity of the gamma-aminobutyric acid GABA¥ transport system. Cloning of two novel high affinity GABA transporters from rat brain. J. Biol. Chem., 267: 21098-21104 (1992).
15. Rebouche, C. J. and Engel, A. G.: Tissue distribution of carnitine biosynthetic enzymes in man. Biochim. Biophys. Acta, 630: 22-29 (1980).
16. van Vlies, N., Wanders, R. J. A. and Vaz, F.: Measurement of carnitine biosynthesis enzyme activities by tandem mass spectrometry: Differences between the mouse and the rat. Anal. Biochem., 354: 132-139 (2006).
17. Englard, S. and Carnicero, H. H.: G-butyrobetaine hydroxylation to carnitine in mammalian kidney. Arch. Biochem. Biophys., 190: 361-364 (1978).
18. Kalaria, R. and Harik, S.: Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimerös disease. Ann. Neurol., 32: 583-586 (1992).
19. Kuratsune, H., Yamaguti, K., Lindh, G., Evengård, B., Hagberg, G., Matsumura, K., Iwase, M., Onoe, H., Takahashi, M., Machii, T., Kanakura, Y., Kitani, T., Långström, B. and Watanabe, Y.: Brain regions involved in fatigue sensation: Reduced acetylcarnitine uptake into the brain. Neuroimage, 17: 1256-1265 (2002).