The human liver-specific homolog of very long-chain acyl-CoA synthetase ischolate: CoA ligase

Unconjugated bile acids must be activated to their CoA thioesters before co njugation to taurine or glycine can occur. A human homolog of very long-cha in acyl-CoA synthetase, hVLCS-H2, has two requisite properties of a bile ac id:CoA ligase, liver specificity and an endoplasmic reticulum subcellular l ocalization. We investigated the ability of this enzyme to activate the pri mary bile acid, cholic acid, to its CoA derivative. When expressed in COS-1 cells, hVLCS-H2 exhibited cholate:CoA ligase (choloyl-CoA synthetase) acti vity with both nonisotopic and radioactive assays. Other long- and very lon g-chain acyl-CoA synthetases were incapable of activating cholate. Endogeno us choloyl-CoA synthetase activity was also detected in liver-derived HepG2 cells but not in kidney-derived COS-1 cells. Our results are consistent wi th a role for hVLCS-H2 in the re-activation and re-conjugation of bile acid s entering liver from the enterohepatic circulation rather than in de novo bile acid synthesis.