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E.P.B. was a Burroughs Wellcome Scholar in Clinical Pharmacology"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,6]]},"abstract":"<jats:sec><jats:title\/><jats:p>Carnitine biosynthesis was investigated in rats with secondary biliary cirrhosis induced by bile duct ligation (BDL) for 4 weeks (n = 5) and in pair-fed, sham-operated control rats (n = 4). Control rats were pair-fed to BDL rats, and all rats were fed an artificial diet with negligible contents of carnitine, butyrobetaine, or trimethyllysine. Biosynthesis of carnitine and its precursors was determined by measuring their excretion in urine and accumulation in the body of the animals. Four weeks after BDL, total carnitine content was increased by 33% in livers from BDL rats when compared with control rats, but was unchanged in skeletal muscle and whole carcass. The plasma total carnitine concentration averaged 29.0 \u00b1 4.1 vs. 46.4 \u00b1 7.3 \u03bcmol\/L in BDL rats and control rats, respectively. Urinary total carnitine excretion was reduced by 56% in BDL rats as compared with control rats. Carnitine biosynthesis was significantly decreased in BDL rats (0.45 \u00b1 0.19 vs. 0.93 \u00b1 0.08 \u03bcmol\/100 g body weight\/d in BDL and control rats, respectively). The tissue content of free and protein-linked trimethyllysine, a carnitine precursor, and trimethyllysine plasma concentrations were not different between BDL and control rats. However, urinary trimethyllysine excretion was increased 5-fold in BDL rats and approximated glomerular filtration. In contrast, urinary excretion of butyrobetaine, the direct carnitine precursor, was decreased by 40% in BDL rats as compared with control rats. Trimethyllysine biosynthesis was not different, but butyrobetaine biosynthesis was decreased by 51% in BDL as compared with control rats. In conclusion, carnitine biosynthesis is decreased in BDL rats as a result of a defect in the conversion of trimethyllysine to butyrobetaine.<\/jats:p><\/jats:sec>","DOI":"10.1053\/jhep.2000.8105","type":"journal-article","created":{"date-parts":[[2004,3,19]],"date-time":"2004-03-19T18:37:43Z","timestamp":1079721463000},"page":"1217-1223","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Decreased carnitine biosynthesis in rats with secondary biliary cirrhosis"],"prefix":"10.1097","volume":"31","author":[{"given":"Stephan","family":"Kr\u00e4henb\u00fchl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric P.","family":"Brass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles L.","family":"Hoppel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2000.8105-BIB1|cit1","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1152\/physrev.1983.63.4.1420","article-title":"Carnitine-metabolism and functions","volume":"63","author":"Bremer","year":"1983","journal-title":"Physiol Rev"},{"key":"10.1053\/jhep.2000.8105-BIB2|cit2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1748-1716.1955.tb01256.x","article-title":"The effects of muscle extracts on the oxidation of palmitic acid by liver slices and homogenates","volume":"34","author":"Fritz","year":"1955","journal-title":"Acta Physiol Scand"},{"key":"10.1053\/jhep.2000.8105-BIB3|cit3","first-page":"2858","article-title":"Possible functions of short-chain and medium-chain carnitine acyltransferases","volume":"41","author":"Bieber","year":"1982","journal-title":"Fed Proc"},{"key":"10.1053\/jhep.2000.8105-BIB4|cit4","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1042\/bj1900495","article-title":"Relationship between acid-soluble carnitine and coenzyme A pools in vivo","volume":"190","author":"Brass","year":"1980","journal-title":"Biochem J"},{"key":"10.1053\/jhep.2000.8105-BIB5|cit5","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/jn\/118.5.541","article-title":"Role of carnitine in human nutrition","volume":"118","author":"Feller","year":"1988","journal-title":"J Nutr"},{"key":"10.1053\/jhep.2000.8105-BIB6|cit6","first-page":"227","article-title":"Protein methylation: chemical, enzymological, and biological significance","volume":"42","author":"Paik","year":"1975","journal-title":"Adv Enzymol Relat Areas Mol Biol"},{"key":"10.1053\/jhep.2000.8105-BIB7|cit7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1042\/bst0140673","article-title":"Inter-tissue relationships in the synthesis and distribution of carnitine","volume":"14","author":"Hoppel","year":"1986","journal-title":"Biochem Soc Trans"},{"key":"10.1053\/jhep.2000.8105-BIB8|cit8","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/jn\/116.5.751","article-title":"e-N-Trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat","volume":"116","author":"Rebouche","year":"1986","journal-title":"J Nutr"},{"key":"10.1053\/jhep.2000.8105-BIB9|cit9","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/jn\/119.12.1907","article-title":"Utilization of dietary precursors for carnitine synthesis in human adults","volume":"119","author":"Rebouche","year":"1989","journal-title":"J Nutr"},{"key":"10.1053\/jhep.2000.8105-BIB10|cit10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1093\/jn\/113.5.979","article-title":"Effect of starvation in the rat on trimethyllysine in peptide linkage","volume":"113","author":"Davis","year":"1983","journal-title":"J Nutr"},{"key":"10.1053\/jhep.2000.8105-BIB11|cit11","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/jn\/116.5.760","article-title":"Effect of starvation on the disposition of free and peptide-linked trimethyllysine in the rat","volume":"116","author":"Davis","year":"1986","journal-title":"J Nutr"},{"key":"10.1053\/jhep.2000.8105-BIB12|cit12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1042\/bj1880521","article-title":"N6-Trimethyl-lysine metabolism. 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