Abstract
Carnitine is indispensable for energy metabolism, since it enables activated fatty acids to enter the mitochondria, where they are broken down via beta-oxidation. Carnitine is probably present in all animal species, and in numerous micro-organisms and plants. In mammals, carnitine homoeostasis is maintained by endogenous synthesis, absorption from dietary sources and efficient tubular reabsorption by the kidney. This review aims to cover the current knowledge of the enzymological, molecular, metabolic and regulatory aspects of mammalian carnitine biosynthesis, with an emphasis on the human and rat.
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- Abe T., Takada K., Ohkawa K., Matsuda M. Purification and characterization of a rat brain aldehyde dehydrogenase able to metabolize gamma-aminobutyraldehyde to gamma-aminobutyric acid. Biochem J. 1990 Jul 1;269(1):25–29. doi: 10.1042/bj2690025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bahl J., Navin T., Manian A. A., Bressler R. Carnitine transport in isolated adult rat heart myocytes and the effect of 7,8-diOH chlorpromazine. Circ Res. 1981 Mar;48(3):378–385. doi: 10.1161/01.res.48.3.378. [DOI] [PubMed] [Google Scholar]
- Barth P. G., Scholte H. R., Berden J. A., Van der Klei-Van Moorsel J. M., Luyt-Houwen I. E., Van 't Veer-Korthof E. T., Van der Harten J. J., Sobotka-Plojhar M. A. An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci. 1983 Dec;62(1-3):327–355. doi: 10.1016/0022-510x(83)90209-5. [DOI] [PubMed] [Google Scholar]
- Berardi S., Stieger B., Wachter S., O'Neill B., Krahenbühl S. Characterization of a sodium-dependent transport system for butyrobetaine into rat liver plasma membrane vesicles. Hepatology. 1998 Aug;28(2):521–525. doi: 10.1002/hep.510280232. [DOI] [PubMed] [Google Scholar]
- Bieber L. L. Carnitine. Annu Rev Biochem. 1988;57:261–283. doi: 10.1146/annurev.bi.57.070188.001401. [DOI] [PubMed] [Google Scholar]
- Bohmer T. Conversion of butyrobetaine to carnitine in the rat in vivo. Biochim Biophys Acta. 1974 May 24;343(3):551–557. [PubMed] [Google Scholar]
- Bohmer T., Hansson V. Androgen-dependent accumulation of carnitine by rat epididymis after injection of [3H]butyrobetaine in vivo. Mol Cell Endocrinol. 1975 Aug;3(2):103–115. doi: 10.1016/0303-7207(75)90057-x. [DOI] [PubMed] [Google Scholar]
- Borum P. R. Variation in tissue carnitine concentrations with age and sex in the rat. Biochem J. 1978 Dec 15;176(3):677–681. doi: 10.1042/bj1760677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bremer J. Carnitine--metabolism and functions. Physiol Rev. 1983 Oct;63(4):1420–1480. doi: 10.1152/physrev.1983.63.4.1420. [DOI] [PubMed] [Google Scholar]
- Buchta R., Nyhan W. L., Broock R., Schragg P. Carnitine in adolescents. J Adolesc Health. 1993 Sep;14(6):440–441. doi: 10.1016/1054-139x(93)90114-5. [DOI] [PubMed] [Google Scholar]
- Burckhardt G., Wolff N. A. Structure of renal organic anion and cation transporters. Am J Physiol Renal Physiol. 2000 Jun;278(6):F853–F866. doi: 10.1152/ajprenal.2000.278.6.F853. [DOI] [PubMed] [Google Scholar]
- Burwinkel B., Kreuder J., Schweitzer S., Vorgerd M., Gempel K., Gerbitz K. D., Kilimann M. W. Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality. Biochem Biophys Res Commun. 1999 Aug 2;261(2):484–487. doi: 10.1006/bbrc.1999.1060. [DOI] [PubMed] [Google Scholar]
- Böhmer T., Eiklid K., Jonsen J. Carnitine uptake into human heart cells in culture. Biochim Biophys Acta. 1977 Mar 17;465(3):627–633. doi: 10.1016/0005-2736(77)90278-4. [DOI] [PubMed] [Google Scholar]
- Carter A. L., Abney T. O., Braver H., Chuang A. H. Localization of gamma-butyrobetaine hydroxylase in the rat testis. Biol Reprod. 1987 Aug;37(1):68–72. doi: 10.1095/biolreprod37.1.68. [DOI] [PubMed] [Google Scholar]
- Carter A. L., Abney T. O., Lapp D. F. Biosynthesis and metabolism of carnitine. J Child Neurol. 1995 Nov;10 (Suppl 2):S3–S7. [PubMed] [Google Scholar]
- Carter A. L., Frenkel R. The role of the kidney in the biosynthesis of carnitine in the rat. J Biol Chem. 1979 Nov 10;254(21):10670–10674. [PubMed] [Google Scholar]
- Casillas E. R., Erickson B. J. Studies on carnitine synthesis in the rat epididymis. J Reprod Fertil. 1975 Aug;44(2):287–291. doi: 10.1530/jrf.0.0440287. [DOI] [PubMed] [Google Scholar]
- Cederblad G., Holm J., Lindstedt G., Lindstedt S., Nordin I., Scherstén T. gamma-Butyrobetaine hydroxylase activity in human and ovine liver and skeletal muscle tissue. FEBS Lett. 1979 Feb 1;98(1):57–60. doi: 10.1016/0014-5793(79)80151-9. [DOI] [PubMed] [Google Scholar]
- Cederblad G. Plasma carnitine and body composition. Clin Chim Acta. 1976 Mar 1;67(2):207–212. doi: 10.1016/0009-8981(76)90261-8. [DOI] [PubMed] [Google Scholar]
- Chern M. K., Pietruszko R. Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase. Biochem Biophys Res Commun. 1995 Aug 15;213(2):561–568. doi: 10.1006/bbrc.1995.2168. [DOI] [PubMed] [Google Scholar]
- Cho Y. O., Leklem J. E. In vivo evidence for a vitamin B-6 requirement in carnitine synthesis. J Nutr. 1990 Mar;120(3):258–265. doi: 10.1093/jn/120.3.258. [DOI] [PubMed] [Google Scholar]
- Christiansen R. Z., Bremer J. Active transport of butyrobetaine and carnitine into isolated liver cells. Biochim Biophys Acta. 1976 Nov 2;448(4):562–577. doi: 10.1016/0005-2736(76)90110-3. [DOI] [PubMed] [Google Scholar]
- Claros M. G., Vincens P. Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem. 1996 Nov 1;241(3):779–786. doi: 10.1111/j.1432-1033.1996.00779.x. [DOI] [PubMed] [Google Scholar]
- Cox R. A., Hoppel C. L. Carnitine and trimethylaminobutyrate synthesis in rat tissues. Biochem J. 1974 Sep;142(3):699–701. doi: 10.1042/bj1420699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis A. T., Hoppel C. L. Effect of starvation on the disposition of free and peptide-linked trimethyllysine in the rat. J Nutr. 1986 May;116(5):760–767. doi: 10.1093/jn/116.5.760. [DOI] [PubMed] [Google Scholar]
- Davis A. T., Ingalls S. T., Hoppel C. L. Determination of free trimethyllysine in plasma and tissue specimens by high-performance liquid chromatography. J Chromatogr. 1984 Mar 9;306:79–87. doi: 10.1016/s0378-4347(00)80871-3. [DOI] [PubMed] [Google Scholar]
- Dunn W. A., Aronson N. N., Jr, Englard S. The effects of 1-amino-D-proline on the production of carnitine from exogenous protein-bound trimethyllysine by the perfused rat liver. J Biol Chem. 1982 Jul 25;257(14):7948–7951. [PubMed] [Google Scholar]
- Dunn W. A., Rettura G., Seifter E., Englard S. Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase. J Biol Chem. 1984 Sep 10;259(17):10764–10770. [PubMed] [Google Scholar]
- Duran M., Loof N. E., Ketting D., Dorland L. Secondary carnitine deficiency. J Clin Chem Clin Biochem. 1990 May;28(5):359–363. [PubMed] [Google Scholar]
- Englard S., Blanchard J. S., Midelfort C. F. Gamma-butyrobetaine hydroxylase: stereochemical course of the hydroxylation reaction. Biochemistry. 1985 Feb 26;24(5):1110–1116. doi: 10.1021/bi00326a007. [DOI] [PubMed] [Google Scholar]
- Englard S., Carnicero H. H. gamma-Butyrobetaine hydroxylation to carnitine in mammalian kidney. Arch Biochem Biophys. 1978 Sep;190(1):361–364. doi: 10.1016/0003-9861(78)90287-4. [DOI] [PubMed] [Google Scholar]
- Englard S., Horwitz L. J., Mills J. T. A simplified method for the measurement of gamma-butyrobetaine hydroxylase activity. J Lipid Res. 1978 Nov;19(8):1057–1063. [PubMed] [Google Scholar]
- Englard S. Hydroxylation of gamma-butyrobetaine to carnitine in human and monkey tissues. FEBS Lett. 1979 Jun 15;102(2):297–300. doi: 10.1016/0014-5793(79)80022-8. [DOI] [PubMed] [Google Scholar]
- Erfle J. D. Hydroxylation of gamma-butyrobetaine by rat and ovine tissues. Biochem Biophys Res Commun. 1975 May 19;64(2):553–557. doi: 10.1016/0006-291x(75)90357-5. [DOI] [PubMed] [Google Scholar]
- Eriksson B. O., Lindstedt S., Nordin I. Hereditary defect in carnitine membrane transport is expressed in skin fibroblasts. Eur J Pediatr. 1988 Aug;147(6):662–663. doi: 10.1007/BF00442488. [DOI] [PubMed] [Google Scholar]
- Fernández Ortega M. F. Effect of dietary lysine level and protein restriction on the lipids and carnitine levels in the liver of pregnant rats. Ann Nutr Metab. 1989;33(3):162–169. doi: 10.1159/000177533. [DOI] [PubMed] [Google Scholar]
- Galland S., Le Borgne F., Bouchard F., Georges B., Clouet P., Grand-Jean F., Demarquoy J. Molecular cloning and characterization of the cDNA encoding the rat liver gamma-butyrobetaine hydroxylase. Biochim Biophys Acta. 1999 Oct 18;1441(1):85–92. doi: 10.1016/s1388-1981(99)00135-3. [DOI] [PubMed] [Google Scholar]
- Galland S., Le Borgne F., Guyonnet D., Clouet P., Demarquoy J. Purification and characterization of the rat liver gamma-butyrobetaine hydroxylase. Mol Cell Biochem. 1998 Jan;178(1-2):163–168. doi: 10.1023/a:1006849713407. [DOI] [PubMed] [Google Scholar]
- Garrow T. A., Brenner A. A., Whitehead V. M., Chen X. N., Duncan R. G., Korenberg J. R., Shane B. Cloning of human cDNAs encoding mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal localization. J Biol Chem. 1993 Jun 5;268(16):11910–11916. [PubMed] [Google Scholar]
- Georges B., Le Borgne F., Galland S., Isoir M., Ecosse D., Grand-Jean F., Demarquoy J. Carnitine transport into muscular cells. Inhibition of transport and cell growth by mildronate. Biochem Pharmacol. 2000 Jun 1;59(11):1357–1363. doi: 10.1016/s0006-2952(00)00265-3. [DOI] [PubMed] [Google Scholar]
- Giannacopoulou C., Evangeliou A., Matalliotakis I., Relakis K., Sbirakis N., Hatzidaki E., Koumandakis E. Effects of gestation age and of birth weight in the concentration of carnitine in the umbilical plasma. Clin Exp Obstet Gynecol. 1998;25(1-2):42–45. [PubMed] [Google Scholar]
- Girgis S., Nasrallah I. M., Suh J. R., Oppenheim E., Zanetti K. A., Mastri M. G., Stover P. J. Molecular cloning, characterization and alternative splicing of the human cytoplasmic serine hydroxymethyltransferase gene. Gene. 1998 Apr 14;210(2):315–324. doi: 10.1016/s0378-1119(98)00085-7. [DOI] [PubMed] [Google Scholar]
- Güneral F. Serum and urine total, free and acylcarnitine levels related to age: assessment of renal handling of carnitine. Turk J Pediatr. 1995 Jul-Sep;37(3):217–222. [PubMed] [Google Scholar]
- Hahn P. The development of carnitine synthesis from gamma-butyrobetaine in the rat. Life Sci. 1981 Mar 2;28(9):1057–1060. doi: 10.1016/0024-3205(81)90753-0. [DOI] [PubMed] [Google Scholar]
- Haigler H. T., Broquist H. P. Carnitine synthesis in rat tissue slices. Biochem Biophys Res Commun. 1974 Feb 4;56(3):676–681. doi: 10.1016/0006-291x(74)90658-5. [DOI] [PubMed] [Google Scholar]
- Hayashi Y., Muranaka Y., Kirimoto T., Asaka N., Miyake H., Matsuura N. Effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on tissue carnitine and lipid levels in rats. Biol Pharm Bull. 2000 Jun;23(6):770–773. doi: 10.1248/bpb.23.770. [DOI] [PubMed] [Google Scholar]
- Hayashi Y., Tajima K., Kirimoto T., Miyake H., Matsuura N. Cardioprotective effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on cardiac dysfunction induced by ischemia/reperfusion in isolated rat hearts. Pharmacology. 2000 Nov;61(4):238–243. doi: 10.1159/000028407. [DOI] [PubMed] [Google Scholar]
- Henderson G. D., Xue G. P., Snoswell A. M. Carnitine and creatine content of tissues of normal and alloxan-diabetic sheep and rats. Comp Biochem Physiol B. 1983;76(2):295–298. doi: 10.1016/0305-0491(83)90073-1. [DOI] [PubMed] [Google Scholar]
- Henderson L. M., Nelson P. J., Henderson L. Mammalian enzymes of trimethyllysine conversion to trimethylaminobutyrate. Fed Proc. 1982 Oct;41(12):2843–2847. [PubMed] [Google Scholar]
- Higashi Y., Yokogawa K., Takeuchi N., Tamai I., Nomura M., Hashimoto N., Hayakawa J. I., Miyamoto K. I., Tsuji A. Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice. J Pharm Pharmacol. 2001 Apr;53(4):527–533. doi: 10.1211/0022357011775631. [DOI] [PubMed] [Google Scholar]
- Hoppel C. L., Weir D. E., Gibbons A. P., Ingalls S. T., Brittain A. T., Brown F. M. Determination of 6-N-trimethyllysine in urine by high-performance liquid chromatography. J Chromatogr. 1983 Jan 14;272(1):43–50. doi: 10.1016/s0378-4347(00)86101-0. [DOI] [PubMed] [Google Scholar]
- Horiuchi M., Kobayashi K., Asaka N., Saheki T. Secondary abnormality of carnitine biosynthesis results from carnitine reabsorptional system defect in juvenile visceral steatosis mice. Biochim Biophys Acta. 1997 Dec 31;1362(2-3):263–268. doi: 10.1016/s0925-4439(97)00089-6. [DOI] [PubMed] [Google Scholar]
- Horiuchi M., Kobayashi K., Yamaguchi S., Shimizu N., Koizumi T., Nikaido H., Hayakawa J., Kuwajima M., Saheki T. Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system. Biochim Biophys Acta. 1994 Apr 12;1226(1):25–30. doi: 10.1016/0925-4439(94)90054-x. [DOI] [PubMed] [Google Scholar]
- Horne D. W., Broquist H. P. Role of lysine and -N-trimethyllysine in carnitine biosynthesis. I. Studies in Neurospora crassa. J Biol Chem. 1973 Mar 25;248(6):2170–2175. [PubMed] [Google Scholar]
- Hulse J. D., Ellis S. R., Henderson L. M. Carnitine biosynthesis. beta-Hydroxylation of trimethyllysine by an alpha-ketoglutarate-dependent mitochondrial dioxygenase. J Biol Chem. 1978 Mar 10;253(5):1654–1659. [PubMed] [Google Scholar]
- Hulse J. D., Henderson L. M. Carnitine biosynthesis. Purification of 4-N'-trimethylaminobutyraldehyde dehydrogenase from beef liver. J Biol Chem. 1980 Feb 10;255(3):1146–1151. [PubMed] [Google Scholar]
- Huszar G. Tissue-specific biosynthesis of epsilon-N-monomethyllysine and epsilon-N-trimethyllysine in skeletal and cardiac muscle myosin: a model for the cell-free study of post-translational amino acid modifications in proteins. J Mol Biol. 1975 May 25;94(3):311–326. doi: 10.1016/0022-2836(75)90205-3. [DOI] [PubMed] [Google Scholar]
- Inoue F., Terada N., Nakajima H., Okochi M., Kodo N., Kizaki Z., Kinugasa A., Sawada T. Effect of sports activity on carnitine metabolism. Measurement of free carnitine, gamma-butyrobetaine and acylcarnitines by tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999 Aug 6;731(1):83–88. doi: 10.1016/s0378-4347(99)00137-1. [DOI] [PubMed] [Google Scholar]
- Izaguirre G., Kikonyogo A., Pietruszko R. Tissue distribution of human aldehyde dehydrogenase E3 (ALDH9): comparison of enzyme activity with E3 protein and mRNA distribution. Comp Biochem Physiol B Biochem Mol Biol. 1997 Sep;118(1):59–64. doi: 10.1016/s0305-0491(97)00022-9. [DOI] [PubMed] [Google Scholar]
- Jakobs B. S., Wanders R. J. Fatty acid beta-oxidation in peroxisomes and mitochondria: the first, unequivocal evidence for the involvement of carnitine in shuttling propionyl-CoA from peroxisomes to mitochondria. Biochem Biophys Res Commun. 1995 Aug 24;213(3):1035–1041. doi: 10.1006/bbrc.1995.2232. [DOI] [PubMed] [Google Scholar]
- Kakimoto Y., Akazawa S. Isolation and identification of N-G,N-G- and N-G,N'-G-dimethyl-arginine, N-epsilon-mono-, di-, and trimethyllysine, and glucosylgalactosyl- and galactosyl-delta-hydroxylysine from human urine. J Biol Chem. 1970 Nov 10;245(21):5751–5758. [PubMed] [Google Scholar]
- Karpati G., Carpenter S., Engel A. G., Watters G., Allen J., Rothman S., Klassen G., Mamer O. A. The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical, and pathophysiologic features. Neurology. 1975 Jan;25(1):16–24. doi: 10.1212/wnl.25.1.16. [DOI] [PubMed] [Google Scholar]
- Kersten S., Seydoux J., Peters J. M., Gonzalez F. J., Desvergne B., Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest. 1999 Jun;103(11):1489–1498. doi: 10.1172/JCI6223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kikonyogo A., Pietruszko R. Aldehyde dehydrogenase from adult human brain that dehydrogenates gamma-aminobutyraldehyde: purification, characterization, cloning and distribution. Biochem J. 1996 May 15;316(Pt 1):317–324. doi: 10.1042/bj3160317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kleber H. P. Bacterial carnitine metabolism. FEMS Microbiol Lett. 1997 Feb 1;147(1):1–9. doi: 10.1111/j.1574-6968.1997.tb10212.x. [DOI] [PubMed] [Google Scholar]
- Kohse K. P., Graser T. A., Fürst P., Franz H. E. Plasma levels of carnitine precursor 6-N-trimethyllysine and maintenance hemodialysis. Kidney Int Suppl. 1987 Oct;22:S128–S131. [PubMed] [Google Scholar]
- Kondo A., Blanchard J. S., Englard S. Purification and properties of calf liver gamma-butyrobetaine hydroxylase. Arch Biochem Biophys. 1981 Dec;212(2):338–346. doi: 10.1016/0003-9861(81)90374-x. [DOI] [PubMed] [Google Scholar]
- Krahenbuhl S., Minkler P. E., Hoppel C. L. Derivatization of isolated endogenous butyrobetaine with 4'-bromophenacyl trifluoromethanesulfonate followed by high-performance liquid chromatography. J Chromatogr. 1992 Jan 3;573(1):3–10. doi: 10.1016/0378-4347(92)80466-4. [DOI] [PubMed] [Google Scholar]
- Krajcovicová-Kudlácková M., Simoncic R., Béderová A., Babinská K., Béder I. Correlation of carnitine levels to methionine and lysine intake. Physiol Res. 2000;49(3):399–402. [PubMed] [Google Scholar]
- Krähenbühl S., Reichen J. Carnitine metabolism in patients with chronic liver disease. Hepatology. 1997 Jan;25(1):148–153. doi: 10.1053/jhep.1997.v25.pm0008985281. [DOI] [PubMed] [Google Scholar]
- Kurys G., Shah P. C., Kikonygo A., Reed D., Ambroziak W., Pietruszko R. Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde. Eur J Biochem. 1993 Dec 1;218(2):311–320. doi: 10.1111/j.1432-1033.1993.tb18379.x. [DOI] [PubMed] [Google Scholar]
- Kuwajima M., Harashima H., Hayashi M., Ise S., Sei M., Lu K. m., Kiwada H., Sugiyama Y., Shima K. Pharmacokinetic analysis of the cardioprotective effect of 3-(2,2, 2-trimethylhydrazinium) propionate in mice: inhibition of carnitine transport in kidney. J Pharmacol Exp Ther. 1999 Apr;289(1):93–102. [PubMed] [Google Scholar]
- Kuwajima M., Lu K., Harashima H., Ono A., Sato I., Mizuno A., Murakami T., Nakajima H., Miyagawa J., Namba M. Carnitine transport defect in fibroblasts of juvenile visceral steatosis (JVS) mouse. Biochem Biophys Res Commun. 1996 Jun 14;223(2):283–287. doi: 10.1006/bbrc.1996.0885. [DOI] [PubMed] [Google Scholar]
- LaBadie J., Dunn W. A., Aronson N. N., Jr Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin. Biochem J. 1976 Oct 15;160(1):85–95. doi: 10.1042/bj1600085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lange H. W., Löwer R., Hempel K. Quantitative determination of N epsilon-methylated lysines in human plasma and urine. Hoppe Seylers Z Physiol Chem. 1973 Feb;354(2):117–120. doi: 10.1515/bchm2.1973.354.1.117. [DOI] [PubMed] [Google Scholar]
- Lange H. W., Löwer R., Hempel K. Verbesserte säulenchromatographische Bestimmung N -methylierter Lysine in physiologischen Flüssigkeiten. J Chromatogr. 1973 Feb 7;76(1):252–254. doi: 10.1016/s0021-9673(01)97803-3. [DOI] [PubMed] [Google Scholar]
- Lehman L. J., Olson A. L., Rebouche C. J. Measurement of epsilon-N-trimethyllysine in human blood plasma and urine. Anal Biochem. 1987 Apr;162(1):137–142. doi: 10.1016/0003-2697(87)90018-2. [DOI] [PubMed] [Google Scholar]
- Lin S. W., Chen J. C., Hsu L. C., Hsieh C. L., Yoshida A. Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence, genomic organization, polymorphism, chromosomal localization, and tissue expression. Genomics. 1996 Jun 15;34(3):376–380. doi: 10.1006/geno.1996.0300. [DOI] [PubMed] [Google Scholar]
- Lindstedt G. Hydroxylation of gamma-butyrobetaine to carnitine in rat liver. Biochemistry. 1967 May;6(5):1271–1282. doi: 10.1021/bi00857a007. [DOI] [PubMed] [Google Scholar]
- Lindstedt G., Lindstedt S. Cofactor requirements of gamma-butyrobetaine hydroxylase from rat liver. J Biol Chem. 1970 Aug 25;245(16):4178–4186. [PubMed] [Google Scholar]
- Lindstedt G., Lindstedt S., Nordin I. Gamma-butyrobetaine hydroxylase in human kidney. Scand J Clin Lab Invest. 1982 Oct;42(6):477–485. [PubMed] [Google Scholar]
- Lindstedt G., Lindstedt S., Nordin I. Purification and properties of gamma-butyrobetaine hydroxylase from Pseudomonas sp AK 1. Biochemistry. 1977 May 17;16(10):2181–2188. doi: 10.1021/bi00629a022. [DOI] [PubMed] [Google Scholar]
- Lindstedt G., Lindstedt S., Olander B., Tofft M. Alpha-ketoglutarate and hydroxylation of gamma-butyrobetaine. Biochim Biophys Acta. 1968 Jun 24;158(3):503–505. doi: 10.1016/0304-4165(68)90317-6. [DOI] [PubMed] [Google Scholar]
- Lindstedt S., Nordin I. Multiple forms of gamma-butyrobetaine hydroxylase (EC 1.14.11.1). Biochem J. 1984 Oct 1;223(1):119–127. doi: 10.1042/bj2230119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lombard K. A., Olson A. L., Nelson S. E., Rebouche C. J. Carnitine status of lactoovovegetarians and strict vegetarian adults and children. Am J Clin Nutr. 1989 Aug;50(2):301–306. doi: 10.1093/ajcn/50.2.301. [DOI] [PubMed] [Google Scholar]
- Lu K. m., Nishimori H., Nakamura Y., Shima K., Kuwajima M. A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse. Biochem Biophys Res Commun. 1998 Nov 27;252(3):590–594. doi: 10.1006/bbrc.1998.9708. [DOI] [PubMed] [Google Scholar]
- Löwer R., Lange H. W., Hempel K. N epsilon-Methylierte Lysine: Abbau und Ausscheidung. Hoppe Seylers Z Physiol Chem. 1972 Oct;353(10):1545–1546. [PubMed] [Google Scholar]
- Marzo A., Curti S. L-Carnitine moiety assay: an up-to-date reappraisal covering the commonest methods for various applications. J Chromatogr B Biomed Sci Appl. 1997 Nov 21;702(1-2):1–20. doi: 10.1016/s0378-4347(97)00376-9. [DOI] [PubMed] [Google Scholar]
- McGarry J. D., Brown N. F. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem. 1997 Feb 15;244(1):1–14. doi: 10.1111/j.1432-1033.1997.00001.x. [DOI] [PubMed] [Google Scholar]
- McGarry J. D., Robles-Valdes C., Foster D. W. Role of carnitine in hepatic ketogenesis. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4385–4388. doi: 10.1073/pnas.72.11.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melegh B., Hermann R., Bock I. Generation of hydroxytrimethyllysine from trimethyllysine limits the carnitine biosynthesis in premature infants. Acta Paediatr. 1996 Mar;85(3):345–350. doi: 10.1111/j.1651-2227.1996.tb14030.x. [DOI] [PubMed] [Google Scholar]
- Melegh B., Tóth G., Adamovich K., Szekely G., Gage D. A., Bieber L. L. Labeled trimethyllysine load depletes unlabeled carnitine in premature infants without evidence of incorporation. Biol Neonate. 1999 Jul;76(1):19–25. doi: 10.1159/000014127. [DOI] [PubMed] [Google Scholar]
- Millington D. S., Kodo N., Norwood D. L., Roe C. R. Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J Inherit Metab Dis. 1990;13(3):321–324. doi: 10.1007/BF01799385. [DOI] [PubMed] [Google Scholar]
- Minkler P. E., Erdos E. A., Ingalls S. T., Griffin R. L., Hoppel C. L. Improved high-performance liquid chromatographic method for the determination of 6-N,N,N-trimethyllysine in plasma and urine: biomedical application of chromatographic figures of merit and amine mobile phase modifiers. J Chromatogr. 1986 Aug 2;380(2):285–299. doi: 10.1016/s0378-4347(00)83657-9. [DOI] [PubMed] [Google Scholar]
- Minkler P. E., Ingalls S. T., Kormos L. S., Weir D. E., Hoppel C. L. Determination of carnitine, butyrobetaine, and betaine as 4'-bromophenacyl ester derivatives by high-performance liquid chromatography. J Chromatogr. 1984 Dec 12;336(2):271–283. doi: 10.1016/s0378-4347(00)85150-6. [DOI] [PubMed] [Google Scholar]
- Morse R. K., Vergnes J. P., Malloy J., McManus I. R. Sites of biological methylation of proteins in cultured chick muscle cells. Biochemistry. 1975 Sep 23;14(19):4316–4325. doi: 10.1021/bi00690a028. [DOI] [PubMed] [Google Scholar]
- Nakanishi T., Hatanaka T., Huang W., Prasad P. D., Leibach F. H., Ganapathy M. E., Ganapathy V. Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. J Physiol. 2001 Apr 15;532(Pt 2):297–304. doi: 10.1111/j.1469-7793.2001.0297f.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nezu J., Tamai I., Oku A., Ohashi R., Yabuuchi H., Hashimoto N., Nikaido H., Sai Y., Koizumi A., Shoji Y. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet. 1999 Jan;21(1):91–94. doi: 10.1038/5030. [DOI] [PubMed] [Google Scholar]
- Noël H., Parvin R., Pande S. V. gamma-butyrobetaine in tissues and serum of fed and starved rats determined by an enzymic radioisotopic procedure. Biochem J. 1984 Jun 15;220(3):701–706. doi: 10.1042/bj2200701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ogawa H., Fujioka M. Purification and characterization of cytosolic and mitochondrial serine hydroxymethyltransferases from rat liver. J Biochem. 1981 Aug;90(2):381–390. doi: 10.1093/oxfordjournals.jbchem.a133484. [DOI] [PubMed] [Google Scholar]
- Olson A. L., Rebouche C. J. gamma-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant. J Nutr. 1987 Jun;117(6):1024–1031. doi: 10.1093/jn/117.6.1024. [DOI] [PubMed] [Google Scholar]
- Paik W. K., Kim S. Protein methylation. Science. 1971 Oct 8;174(4005):114–119. doi: 10.1126/science.174.4005.114. [DOI] [PubMed] [Google Scholar]
- Pande S. V., Parvin R. Clofibrate enhancement of mitochondrial carnitine transport system of rat liver and augmentation of liver carnitine and gamma-butyrobetaine hydroxylase activity by thyroxine. Biochim Biophys Acta. 1980 Mar 21;617(3):363–370. doi: 10.1016/0005-2760(80)90002-8. [DOI] [PubMed] [Google Scholar]
- Panter R. A., Mudd J. B. Carnitine levels in some higher plants. FEBS Lett. 1969 Oct 21;5(2):169–170. doi: 10.1016/0014-5793(69)80322-4. [DOI] [PubMed] [Google Scholar]
- Park K. S., Lee H. W., Hong S. Y., Shin S., Kim S., Paik W. K. Determination of methylated amino acids in human serum by high-performance liquid chromatography. J Chromatogr. 1988 May 25;440:225–230. doi: 10.1016/s0021-9673(00)94526-6. [DOI] [PubMed] [Google Scholar]
- Parvin R., Gianoulakis C., Pande S. V., Chrétien M. Effect of pituitary tumor MtT-F4 on carnitine levels in the serum, liver and heart of rats. Life Sci. 1981 Sep 7;29(10):1047–1049. doi: 10.1016/0024-3205(81)90465-3. [DOI] [PubMed] [Google Scholar]
- Paul H. S., Adibi S. A. Leucine oxidation and protein turnover in clofibrate-induced muscle protein degradation in rats. J Clin Invest. 1980 Jun;65(6):1285–1293. doi: 10.1172/JCI109791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paul H. S., Gleditsch C. E., Adibi S. A. Mechanism of increased hepatic concentration of carnitine by clofibrate. Am J Physiol. 1986 Sep;251(3 Pt 1):E311–E315. doi: 10.1152/ajpendo.1986.251.3.E311. [DOI] [PubMed] [Google Scholar]
- Paul H. S., Sekas G., Adibi S. A. Carnitine biosynthesis in hepatic peroxisomes. Demonstration of gamma-butyrobetaine hydroxylase activity. Eur J Biochem. 1992 Feb 1;203(3):599–605. doi: 10.1111/j.1432-1033.1992.tb16589.x. [DOI] [PubMed] [Google Scholar]
- Prasad P. D., Huang W., Ramamoorthy S., Carter A. L., Leibach F. H., Ganapathy V. Sodium-dependent carnitine transport in human placental choriocarcinoma cells. Biochim Biophys Acta. 1996 Oct 2;1284(1):109–117. doi: 10.1016/0005-2736(96)00126-5. [DOI] [PubMed] [Google Scholar]
- Prescott A. G., Lloyd M. D. The iron(II) and 2-oxoacid-dependent dioxygenases and their role in metabolism. Nat Prod Rep. 2000 Aug;17(4):367–383. doi: 10.1039/a902197c. [DOI] [PubMed] [Google Scholar]
- Ramsay R. R., Gandour R. D., van der Leij F. R. Molecular enzymology of carnitine transfer and transport. Biochim Biophys Acta. 2001 Mar 9;1546(1):21–43. doi: 10.1016/s0167-4838(01)00147-9. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J., Bosch E. P., Chenard C. A., Schabold K. J., Nelson S. E. Utilization of dietary precursors for carnitine synthesis in human adults. J Nutr. 1989 Dec;119(12):1907–1913. doi: 10.1093/jn/119.12.1907. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J. Carnitine function and requirements during the life cycle. FASEB J. 1992 Dec;6(15):3379–3386. [PubMed] [Google Scholar]
- Rebouche C. J. Carnitine movement across muscle cell membranes. Studies in isolated rat muscle. Biochim Biophys Acta. 1977 Nov 15;471(1):145–155. doi: 10.1016/0005-2736(77)90402-3. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J. Effect of dietary carnitine isomers and gamma-butyrobetaine on L-carnitine biosynthesis and metabolism in the rat. J Nutr. 1983 Oct;113(10):1906–1913. doi: 10.1093/jn/113.10.1906. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J., Engel A. G. Carnitine transport in cultured muscle cells and skin fibroblasts from patients with primary systemic carnitine deficiency. In Vitro. 1982 May;18(5):495–500. doi: 10.1007/BF02796479. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J., Engel A. G. Significance of renal gamma-butyrobetaine hydroxylase for carnitine biosynthesis in man. J Biol Chem. 1980 Sep 25;255(18):8700–8705. [PubMed] [Google Scholar]
- Rebouche C. J., Engel A. G. Tissue distribution of carnitine biosynthetic enzymes in man. Biochim Biophys Acta. 1980 Jun 5;630(1):22–29. doi: 10.1016/0304-4165(80)90133-6. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J., Lehman L. J., Olson L. epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat. J Nutr. 1986 May;116(5):751–759. doi: 10.1093/jn/116.5.751. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J., Lombard K. A., Chenard C. A. Renal adaptation to dietary carnitine in humans. Am J Clin Nutr. 1993 Nov;58(5):660–665. doi: 10.1093/ajcn/58.5.660. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J., Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr. 1998;18:39–61. doi: 10.1146/annurev.nutr.18.1.39. [DOI] [PubMed] [Google Scholar]
- Rebouche C. J. Sites and regulation of carnitine biosynthesis in mammals. Fed Proc. 1982 Oct;41(12):2848–2852. [PubMed] [Google Scholar]
- Robles-Valdes C., McGarry J. D., Foster D. W. Maternal-fetal carnitine relationship and neonatal ketosis in the rat. J Biol Chem. 1976 Oct 10;251(19):6007–6012. [PubMed] [Google Scholar]
- Rüetschi U., Nordin I., Odelhög B., Jörnvall H., Lindstedt S. gamma-Butyrobetaine hydroxylase. Structural characterization of the Pseudomonas enzyme. Eur J Biochem. 1993 May 1;213(3):1075–1080. doi: 10.1111/j.1432-1033.1993.tb17855.x. [DOI] [PubMed] [Google Scholar]
- Sachan D. S., Broquist H. P. Synthesis of carnitine from epsilon-N-trimethyllysine in post mitochondrial fractions of Neurospora crassa. Biochem Biophys Res Commun. 1980 Sep 30;96(2):870–875. doi: 10.1016/0006-291x(80)91436-9. [DOI] [PubMed] [Google Scholar]
- Sachan D. S., Hoppel C. L. Carnitine biosynthesis. Hydroxylation of N6-trimethyl-lysine to 3-hydroxy-N6-trimethyl-lysine. Biochem J. 1980 May 15;188(2):529–534. doi: 10.1042/bj1880529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sandor A., Cseko J., Kispal G., Alkonyi I. Surplus acylcarnitines in the plasma of starved rats derive from the liver. J Biol Chem. 1990 Dec 25;265(36):22313–22316. [PubMed] [Google Scholar]
- Sandor A., Hoppel C. L. Butyrobetaine availability in liver is a regulatory factor for carnitine biosynthesis in rat. Flux through butyrobetaine hydroxylase in fasting state. Eur J Biochem. 1989 Nov 20;185(3):671–675. doi: 10.1111/j.1432-1033.1989.tb15164.x. [DOI] [PubMed] [Google Scholar]
- Sandor A., Minkler P. E., Ingalls S. T., Hoppel C. L. An enzymatic method for the determination of butyrobetaine via conversion to carnitine after isolation by high performance liquid chromatography. Clin Chim Acta. 1988 Aug 15;176(1):17–27. doi: 10.1016/0009-8981(88)90170-2. [DOI] [PubMed] [Google Scholar]
- Schmidt-Sommerfeld E., Werner D., Penn D. Carnitine plasma concentrations in 353 metabolically healthy children. Eur J Pediatr. 1988 May;147(4):356–360. doi: 10.1007/BF00496410. [DOI] [PubMed] [Google Scholar]
- Scholte H. R., Rodrigues Pereira R., de Jonge P. C., Luyt-Houwen I. E., Hedwig M., Verduin M., Ross J. D. Primary carnitine deficiency. J Clin Chem Clin Biochem. 1990 May;28(5):351–357. [PubMed] [Google Scholar]
- Shoji Y., Koizumi A., Kayo T., Ohata T., Takahashi T., Harada K., Takada G. Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q. Am J Hum Genet. 1998 Jul;63(1):101–108. doi: 10.1086/301911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simkhovich B. Z., Shutenko Z. V., Meirena D. V., Khagi K. B., Mezapuķe R. J., Molodchina T. N., Kalviņs I. J., Lukevics E. 3-(2,2,2-Trimethylhydrazinium)propionate (THP)--a novel gamma-butyrobetaine hydroxylase inhibitor with cardioprotective properties. Biochem Pharmacol. 1988 Jan 15;37(2):195–202. doi: 10.1016/0006-2952(88)90717-4. [DOI] [PubMed] [Google Scholar]
- Spaniol M., Brooks H., Auer L., Zimmermann A., Solioz M., Stieger B., Krähenbühl S. Development and characterization of an animal model of carnitine deficiency. Eur J Biochem. 2001 Mar;268(6):1876–1887. [PubMed] [Google Scholar]
- Stanley C. A., DeLeeuw S., Coates P. M., Vianey-Liaud C., Divry P., Bonnefont J. P., Saudubray J. M., Haymond M., Trefz F. K., Breningstall G. N. Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann Neurol. 1991 Nov;30(5):709–716. doi: 10.1002/ana.410300512. [DOI] [PubMed] [Google Scholar]
- Stanley C. A. New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. Adv Pediatr. 1987;34:59–88. [PubMed] [Google Scholar]
- Stein R., Englard S. Properties of rat 6-N-trimethyl-L-lysine hydroxylases: similarities among the kidney, liver, heart, and skeletal muscle activities. Arch Biochem Biophys. 1982 Aug;217(1):324–331. doi: 10.1016/0003-9861(82)90508-2. [DOI] [PubMed] [Google Scholar]
- Stein R., Englard S. The use of a tritium release assay to measure 6-N-trimethyl-L-lysine hydroxylase activity: synthesis of 6-N-[3-3H]trimethyl-DL-lysine. Anal Biochem. 1981 Sep 1;116(1):230–236. doi: 10.1016/0003-2697(81)90349-3. [DOI] [PubMed] [Google Scholar]
- Takiyama N., Matsumoto K. Age-and sex-related differences of serum carnitine in a Japanese population. J Am Coll Nutr. 1998 Feb;17(1):71–74. doi: 10.1080/07315724.1998.10720458. [DOI] [PubMed] [Google Scholar]
- Tamai I., China K., Sai Y., Kobayashi D., Nezu J., Kawahara E., Tsuji A. Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney. Biochim Biophys Acta. 2001 Jun 6;1512(2):273–284. doi: 10.1016/s0005-2736(01)00328-5. [DOI] [PubMed] [Google Scholar]
- Tamai I., Ohashi R., Nezu J., Yabuuchi H., Oku A., Shimane M., Sai Y., Tsuji A. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem. 1998 Aug 7;273(32):20378–20382. doi: 10.1074/jbc.273.32.20378. [DOI] [PubMed] [Google Scholar]
- Tang N. L., Ganapathy V., Wu X., Hui J., Seth P., Yuen P. M., Wanders R. J., Fok T. F., Hjelm N. M. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet. 1999 Apr;8(4):655–660. doi: 10.1093/hmg/8.4.655. [DOI] [PubMed] [Google Scholar]
- Tanphaichitr V., Broquist H. P. Role of lysine and -N-trimethyllysine in carnitine biosynthesis. II. Studies in the rat. J Biol Chem. 1973 Mar 25;248(6):2176–2181. [PubMed] [Google Scholar]
- Tanphaichitr V., Broquist H. P. Site of carnitine biosynthesis in the rat. J Nutr. 1974 Dec;104(12):1669–1673. doi: 10.1093/jn/104.12.1669. [DOI] [PubMed] [Google Scholar]
- Tanphaichitr V., Horne D. W., Broquist H. P. Lysine, a precursor of carnitine in the rat. J Biol Chem. 1971 Oct 25;246(20):6364–6366. [PubMed] [Google Scholar]
- Tein I., Bukovac S. W., Xie Z. W. Characterization of the human plasmalemmal carnitine transporter in cultured skin fibroblasts. Arch Biochem Biophys. 1996 May 15;329(2):145–155. doi: 10.1006/abbi.1996.0203. [DOI] [PubMed] [Google Scholar]
- Tein I., De Vivo D. C., Bierman F., Pulver P., De Meirleir L. J., Cvitanovic-Sojat L., Pagon R. A., Bertini E., Dionisi-Vici C., Servidei S. Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. Pediatr Res. 1990 Sep;28(3):247–255. doi: 10.1203/00006450-199009000-00020. [DOI] [PubMed] [Google Scholar]
- Terada N., Inoue F., Okochi M., Nakajima H., Kizaki Z., Kinugasa A., Sawada T. Measurement of carnitine precursors, epsilon-trimethyllysine and gamma-butyrobetaine in human serum by tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999 Aug 6;731(1):89–95. doi: 10.1016/s0378-4347(99)00112-7. [DOI] [PubMed] [Google Scholar]
- Treem W. R., Stanley C. A., Finegold D. N., Hale D. E., Coates P. M. Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts. N Engl J Med. 1988 Nov 17;319(20):1331–1336. doi: 10.1056/NEJM198811173192006. [DOI] [PubMed] [Google Scholar]
- Vaz F. M., Fouchier S. W., Ofman R., Sommer M., Wanders R. J. Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. J Biol Chem. 2000 Mar 10;275(10):7390–7394. doi: 10.1074/jbc.275.10.7390. [DOI] [PubMed] [Google Scholar]
- Vaz F. M., Ofman R., Westinga K., Back J. W., Wanders R. J. Molecular and Biochemical Characterization of Rat epsilon -N-Trimethyllysine Hydroxylase, the First Enzyme of Carnitine Biosynthesis. J Biol Chem. 2001 Jun 28;276(36):33512–33517. doi: 10.1074/jbc.M105929200. [DOI] [PubMed] [Google Scholar]
- Vaz F. M., Scholte H. R., Ruiter J., Hussaarts-Odijk L. M., Pereira R. R., Schweitzer S., de Klerk J. B., Waterham H. R., Wanders R. J. Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency. Hum Genet. 1999 Jul-Aug;105(1-2):157–161. doi: 10.1007/s004399900105. [DOI] [PubMed] [Google Scholar]
- Vaz F. M., van Gool S., Ofman R., IJlst L., Wanders R. J. Carnitine biosynthesis. Purification of gamma-butyrobetaine hydroxylase from rat liver. Adv Exp Med Biol. 1999;466:117–124. [PubMed] [Google Scholar]
- Vaz F. M., van Gool S., Ofman R., Ijlst L., Wanders R. J. Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase. Biochem Biophys Res Commun. 1998 Sep 18;250(2):506–510. doi: 10.1006/bbrc.1998.9343. [DOI] [PubMed] [Google Scholar]
- Verhoeven N. M., Roe D. S., Kok R. M., Wanders R. J., Jakobs C., Roe C. R. Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondrial reactions in cultured fibroblasts. J Lipid Res. 1998 Jan;39(1):66–74. [PubMed] [Google Scholar]
- Vijayasarathy C., Khan-Siddiqui L., Murthy S. N., Bamji M. S. Rise in plasma trimethyllysine levels in humans after oral lysine load. Am J Clin Nutr. 1987 Nov;46(5):772–777. doi: 10.1093/ajcn/46.5.772. [DOI] [PubMed] [Google Scholar]
- Vreken P., van Lint A. E., Bootsma A. H., Overmars H., Wanders R. J., van Gennip A. H. Rapid diagnosis of organic acidemias and fatty-acid oxidation defects by quantitative electrospray tandem-MS acyl-carnitine analysis in plasma. Adv Exp Med Biol. 1999;466:327–337. doi: 10.1007/0-306-46818-2_38. [DOI] [PubMed] [Google Scholar]
- Wang Y., Ye J., Ganapathy V., Longo N. Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2356–2360. doi: 10.1073/pnas.96.5.2356. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willner J. H., Ginsburg S., Dimauro S. Active transport of carnitine into skeletal muscle. Neurology. 1978 Jul;28(7):721–724. doi: 10.1212/wnl.28.7.721. [DOI] [PubMed] [Google Scholar]
- Wu X., George R. L., Huang W., Wang H., Conway S. J., Leibach F. H., Ganapathy V. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315–327. doi: 10.1016/s0005-2736(00)00189-9. [DOI] [PubMed] [Google Scholar]
- Wu X., Huang W., Prasad P. D., Seth P., Rajan D. P., Leibach F. H., Chen J., Conway S. J., Ganapathy V. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482–1492. [PubMed] [Google Scholar]
- Wu X., Prasad P. D., Leibach F. H., Ganapathy V. cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589–595. doi: 10.1006/bbrc.1998.8669. [DOI] [PubMed] [Google Scholar]
- Yabuuchi H., Tamai I., Nezu J., Sakamoto K., Oku A., Shimane M., Sai Y., Tsuji A. Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768–773. [PubMed] [Google Scholar]
- Zaspel B. J., Sheridan K. J., Henderson L. M. Transport and metabolism of carnitine precursors in various organs of the rat. Biochim Biophys Acta. 1980 Aug 1;631(1):192–202. doi: 10.1016/0304-4165(80)90067-7. [DOI] [PubMed] [Google Scholar]