Enzymes involved in l-carnitine biosynthesis are expressed by small intestinal enterocytes in mice: Implications for gut health

Journal of Crohn's and Colitis

Volumn 7, Issue 6, 2013, Pages

  Shekhawat, Prem S ^a   Sonne, Srinivas ^a   Carter, A Lee ^a   Matern, Dietrich ^b   Ganapathy, Vadivel ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b Mayo Clinic College of Medicine   (United States)

Author keywords

Butyrobetaine hydroxylase; Carnitine; Crohn's disease; Gut inflammation; Ulcerative colitis

Indexed keywords

4 TRIMETHYLAMINOBUTYRALDEHYDE DEHYDROGENASE; 6 N TRIMETHYLLYSINE DIOXEGENASE; CARNITINE; ENZYME; GAMMA BUTYROBETAINE DIOXYGENASE; GLYCINE HYDROXYMETHYLTRANSFERASE; GLYCINE HYDROXYMETHYLTRANSFERASE 1; GLYCINE HYDROXYMETHYLTRANSFERASE 2; RNA POLYMERASE; UNCLASSIFIED DRUG;

AMINO ACID SYNTHESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COLON MUCOSA; CONTROLLED STUDY; CROHN DISEASE; ENZYME ACTIVITY; ENZYME LOCALIZATION; EX VIVO STUDY; FATTY ACID OXIDATION; GENE EXPRESSION; IN SITU HYBRIDIZATION; IN VITRO STUDY; INTESTINE EPITHELIUM CELL; MOUSE; NONHUMAN; NUCLEIC ACID ANALYSIS; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; TISSUE SECTION;

ALDEHYDE OXIDOREDUCTASES; ANIMALS; CARNITINE; ENTEROCYTES; GAMMA-BUTYROBETAINE DIOXYGENASE; GENE EXPRESSION; GLYCINE HYDROXYMETHYLTRANSFERASE; IN SITU HYBRIDIZATION; INTESTINAL MUCOSA; INTESTINE, SMALL; MICE; MICE, INBRED C3H; MIXED FUNCTION OXYGENASES; REAL-TIME POLYMERASE CHAIN REACTION;

EID: 84877028600     PISSN: 18739946     EISSN: 18764479     Source Type: Journal    
DOI: 10.1016/j.crohns.2012.08.011     Document Type: Article

References (47)

1. 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, 96:2356-2360.
2. Rebouche C.J. Kinetics, pharmacokinetics, and regulation of l-carnitine and acetyl-l-carnitine metabolism. Ann N Y Acad Sci 2004, 1033:30-41.
3. Nezu J., Tamai I., Oku A., Ohashi R., Yabuuchi H., Hashimoto N., et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999, 21:91-94.
4. Wang Y., Kelly M.A., Cowan T.M., Longo N. A missense mutation in the OCTN2 gene associated with residual carnitine transport activity. Hum Mutat 2000, 15:238-245.
5. Spiekerkoetter U., Huener G., Baykal T., Demirkol M., Duran M., Wanders R., et al. Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2. J Inherit Metab Dis 2003, 26:613-615.
6. Cederbaum S.D., Koo-McCoy S., Tein I., Hsu B.Y., Ganguly A., Vilain E., et al. Carnitine membrane transporter deficiency: a long-term follow up and OCTN2 mutation in the first documented case of primary carnitine deficiency. Mol Genet Metab 2002, 77:195-201.
7. Rinaldo P., Matern D., Bennett M.J. Fatty acid oxidation disorders. Annu Rev Physiol 2002, 64:477-502.
8. Rinaldo P., Raymond K., Al-Odaib A., Bennett M.J. Clinical and biochemical features of fatty acid oxidation disorders. Curr Opin Pediatr 1998, 10:615-621.
9. Rebouche C.J. Carnitine function and requirements during the life cycle. FASEB J 1992, 6:3379-3386.
10. 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, 250:506-510.
11. Vaz F.M., Wanders R.J. Carnitine biosynthesis in mammals. Biochem J 2002, 361:417-429.
12. Johnson J.A. l-Carnitine for treatment of distal ulcerative colitis. Gastroenterology 1992, 103:1709-1710.
13. Giancaterini A., Mingrone G., De Gaetano A., Capristo E., Calvani M., Caso V., et al. Effects of propyonil-l-carnitine topical irrigation in distal ulcerative colitis: a preliminary report. Am J Gastroenterol 2001, 96:2275-2276.
14. Demirkol M., Sewell A.C., Bohles H. The variation of carnitine content in human blood cells during disease-a study in bacterial infection and inflammatory bowel disease. Eur J Pediatr 1994, 153:565-568.
15. Roediger W.E., Nance S. Selective reduction of fatty acid oxidation in colonocytes: correlation with ulcerative colitis. Lipids 1990, 25:646-652.
16. Johnson J.A. l-Carnitine for treatment of nonspecific proctosigmoiditis. Dis Colon Rectum 1993, 36:518.
17. Peltekova V.D., Wintle R.F., Rubin L.A., Amos C.I., Huang Q., Gu X., et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 2004, 36:471-475.
18. Newman B., Gu X., Wintle R., Cescon D., Yazdanpanah M., Liu X., et al. A risk haplotype in the solute carrier family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease. Gastroenterology 2005, 128:260-269.
19. Babusukumar U., Wang T., McGuire E., Broeckel U., Kugathasan S. Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn's disease. Am J Gastroenterol 2006, 101:1354-1361.
20. Bene J., Magyari L., Talian G., Komlosi K., Gasztonyi B., Tari B., et al. Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn's disease. World J Gastroenterol 2006, 12:5550-5553.
21. Ferraris A., Torres B., Knafelz D., Barabino A., Lionetti P., de Angelis G.L., et al. Relationship between CARD15, SLC22A4/5, and DLG5 polymorphisms and early-onset inflammatory bowel diseases: an Italian multicentric study. Inflamm Bowel Dis 2006, 12:355-361.
22. Gazouli M., Mantzaris G., Archimandritis A.J., Nasioulas G., Anagnou N.P. Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease. World J Gastroenterol 2005, 11:7525-7530.
23. Fisher S.A., Hampe J., Onnie C.M., Daly M.J., Curley C., Purcell S., et al. Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn disease. Hum Mutat 2006, 27:778-785.
24. Shekhawat P.S., Srinivas S.R., Matern D., Bennett M.J., Boriack R., George V., et al. Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice. Mol Genet Metab 2007, 92:315-324.
25. Talian G., Lakner L., Bene J., Komlosi K., Horvath K., Gasztonyi B., et al. Plasma carnitine ester profiles in Crohn's disease and ulcerative colitis patients with different IGR2230a_1 genotypes. Int J Immunogenet 2009, 36:329-335.
26. Bene J., Komlosi K., Magyari L., Talian G., Horvath K., Gasztonyi B., et al. Plasma carnitine ester profiles in Crohn's disease patients characterized for SLC22A4 C1672T and SLC22A5 G-207C genotypes. Br J Nutr 2007, 98:345-350.
27. Fortin G., Yurchenko K., Collette C., Rubio M., Villani A.C., Bitton A., et al. l-Carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation. Clin Exp Immunol 2009, 156:161-171.
28. Derin N., Agac A., Bayram Z., Asar M., Izgut-Uysal V.N. Effects of l-carnitine on neutrophil-mediated ischemia-reperfusion injury in rat stomach. Cell Biochem Funct 2006, 24:437-442.
29. Mikhailova T.L., Sishkova E., Poniewierka E., Zhidkov K.P., Bakulin I.G., Kupcinskas L. Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment. Aliment Pharmacol Ther 2011, 34:1088-1097.
30. Henderson L.M., Nelson P.J., Henderson L. Mammalian enzymes of trimethyllysine conversion to trimethylaminobutyrate. Fed Proc 1982, 41:2843-2847.
31. Strijbis K., Vaz F.M., Distel B. Enzymology of the carnitine biosynthesis pathway. IUBMB Life 2010, 62:357-362.
32. Baisden B., Sonne S., Joshi R.M., Ganapathy V., Shekhawat P.S. Antenatal dexamethasone treatment leads to changes in gene expression in a murine late placenta. Placenta 2007, 28:1082-1090.
33. Carter A.L., Stratman F.W. A rapid and sensitive assay of gamma-butyrobetaine hydroxylase. FEBS Lett 1980, 111:112-114.
34. Stevens R.D., Hillman S.L., Worthy S., Sanders D., Millington D.S. Assay for free and total carnitine in human plasma using tandem mass spectrometry. Clin Chem 2000, 46:727-729.
35. Smith E.H., Matern D. Acylcarnitine analysis by tandem mass spectrometry. Curr Protoc Hum Genet 2010, 18:11-20. Chapter 17:Unit 17.
36. Oey N.A., van Vlies N., Wijburg F.A., Wanders R.J., Attie-Bitach T., Vaz F.M. l-Carnitine is synthesized in the human fetal-placental unit: potential roles in placental and fetal metabolism. Placenta 2006, 27:841-846.
37. Fitch M.D., Fleming S.E. Metabolism of short-chain fatty acids by rat colonic mucosa in vivo. Am J Physiol 1999, 277:G31-G40.
38. Jorgensen J., Mortensen P.B. Utilization of short-chain fatty acids by colonic mucosal tissue strips. A new method of assessing colonic mucosal metabolism. Scand J Gastroenterol 2000, 35:659-666.
39. Hijova E., Chmelarova A. Short chain fatty acids and colonic health. Bratisl Lek Listy 2007, 108:354-358.
40. Duran J.M., Peral M.J., Calonge M.L., Ilundain A.A. Functional characterization of intestinal l-carnitine transport. J Membr Biol 2002, 185:65-74.
41. Kato Y., Sugiura M., Sugiura T., Wakayama T., Kubo Y., Kobayashi D., et al. Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Mol Pharmacol 2006, 70:829-837.
42. Fujiya M., Inaba Y., Musch M.W., Hu S., Kohgo Y., Chang E.B. Cytokine regulation of OCTN2 expression and activity in small and large intestine. Inflamm Bowel Dis 2011, 17:907-916.
43. D'Argenio G., Calvani M., Casamassimi A., Petillo O., Margarucci S., Rienzo M., et al. Experimental colitis: decreased Octn2 and Atb0+ expression in rat colonocytes induces carnitine depletion that is reversible by carnitine-loaded liposomes. FASEB J 2006, 20:2544-2546.
44. Hirai T., Fukui Y., Motojima K. PPARalpha agonists positively and negatively regulate the expression of several nutrient/drug transporters in mouse small intestine. Biol Pharm Bull 2007, 30:2185-2190.
45. Radtke F., Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science 2005, 307:1904-1909.
46. Lamhonwah A.M., Olpin S.E., Pollitt R.J., Vianey-Saban C., Divry P., Guffon N., et al. Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. Am J Med Genet 2002, 111:271-284.
47. Girardin M., Dionne S., Goyette P., Rioux J., Bitton A., Elimrani I., et al. Expression and functional analysis of intestinal organic cation/L-carnitine transporter (OCTN) in Crohn's disease. J Crohns Colitis 2012, 6:189-197.