The human liver-specific homolog of very long-chain acyl-CoA synthetase is cholate:CoA ligase.
Unconjugated bile acids must be activated to their CoA thioesters before conjugation to taurine or glycine can occur. A human homolog of very long-chain acyl-CoA synthetase, hVLCS-H2, has two requisite properties of a bile acid:CoA ligase, liver specificity and an endoplasmic reticulum subcellular localization. We investigated the ability of this enzyme to activate the primary bile acid, cholic acid, to its CoA derivative. When expressed in COS-1 cells, hVLCS-H2 exhibited cholate:CoA ligase (choloyl-CoA synthetase) activity with both non-isotopic and radioactive assays. Other long- and very long-chain acyl-CoA synthetases were incapable of activating cholate. Endogenous choloyl-CoA synthetase activity was also detected in liver-derived HepG2 cells but not in kidney-derived COS-1 cells. Our results are consistent with a role for hVLCS-H2 in the re-activation and re-conjugation of bile acids entering liver from the enterohepatic circulation rather than in de novo bile acid synthesis.
Steinberg
S J
SJ
Kennedy Krieger Institute and the Departments of Neurology and Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mihalik
S J
SJ
Kim
D G
DG
Cuebas
D A
DA
Watkins
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019826:Cholic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003066:Coenzyme A Ligases / Q000737:chemistry* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013379:Substrate Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D005227:Fatty Acids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; C019890:choloyl-CoA synthetase; D019826:Cholic Acid