The Human Liver-specific Homolog of Very Long-chain Acyl-CoA Synthetase Is Cholate:CoA Ligase

Steinberg, Steven J.; Mihalik, Stephanie J.; Kim, Do G.; Cuebas, Dean; Watkins, Paul A.

doi:10.1074/jbc.c000015200

Cited by 64 publications

(48 citation statements)

References 26 publications

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“…Acids-We previously showed that when expressed in COS-1 cells, hBACS (formerly called hVLCS-H2, a member of the VLCS/fatty acid transport protein family of acyl-CoA synthetases) catalyzes the activation of cholic acid to its CoA derivative (7). This observation was consistent with the tissue (liver) and subcellular (endoplasmic reticulum) distribution of this protein (17,18).…”

Section: Hbacs Catalyzes Activation Of Primary and Secondary Bilementioning

confidence: 55%

“…In the experiments shown in Figs. 1C and 3B, the gradient program for elution of bile acyl-CoA derivatives from the reverse-phase HPLC column (25-65% solvent B over 30 min), which deviated from the previously described method (25-50% solvent B over 25 min) (7). The unlabeled THCA used in these experiments also contained ⌬24-THCA (8%, w/w).…”

Section: Methodsmentioning

confidence: 85%

“…We recently demonstrated that human very long-chain acylCoA synthetase homolog 2 (hVLCS-H2), a liver-specific member of the protein family that includes very long-chain acyl-CoA synthetases (VLCSs) and fatty acid transport proteins, is a choloyl-CoA synthetase (7). We hypothesized that a major function of this protein is to activate recycled bile acids prior to their re-conjugation.…”

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confidence: 99%

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Participation of Two Members of the Very Long-chain Acyl-CoA Synthetase Family in Bile Acid Synthesis and Recycling

Mihalik¹,

Steinberg²,

Pei³

et al. 2002

Journal of Biological Chemistry

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105

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275, 15605-15608). We now show that this enzyme also activates chenodeoxycholate, the secondary bile acids deoxycholate and lithocholate, and 3␣,7␣,12␣-trihydroxy-5␤-cholestanoic acid. In contrast, VLCS activated 3␣,7␣,12␣-trihydroxy-5␤-cholestanoate, but did not utilize any of the C 24 bile acids as substrates. We hypothesize that the primary function of homolog 2 is in the reactivation and recycling of C 24 bile acids, whereas VLCS participates in the de novo synthesis pathway. Results of in situ hybridization, topographic orientation, and inhibition studies are consistent with the proposed roles of these enzymes in bile acid metabolism.

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Section: Hbacs Catalyzes Activation Of Primary and Secondary Bilementioning

confidence: 55%

Section: Methodsmentioning

confidence: 85%

mentioning

confidence: 99%

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Participation of Two Members of the Very Long-chain Acyl-CoA Synthetase Family in Bile Acid Synthesis and Recycling

Mihalik¹,

Steinberg²,

Pei³

et al. 2002

Journal of Biological Chemistry

Self Cite

105

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“…BA conjugation reactions are catalyzed by two liver-enriched enzymes, bile acid-CoA ligase (BAL) and bile acid-CoA:amino acid Nacyltransferase (BAT) (1,14). BAL activities are associated with rat BAL protein (16) and human very long chain acyl-CoA synthase homolog 2 (VLACSR-H2) protein (17), but enzymatic analysis of BAL protein has not been performed in the mouse. Because the mouse very long chain acyl-CoA synthase-related (VLACSR) gene, which is highly expressed only in liver (18) as well as rat BAL and human VLACSR-H2 genes, has a high homology to these proteins (16), it was reasonable to assume that the VLACSR gene might be the mouse homolog for the BAL gene.…”

mentioning

confidence: 99%

Hepatocyte Nuclear Factor 4α Is a Central Regulator of Bile Acid Conjugation

Inoue

et al. 2004

Journal of Biological Chemistry

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Hepatocyte nuclear factor 4␣ (HNF4␣) has an important role in regulating the expression of liver-specific genes. Because bile acids are produced from cholesterol in liver and many enzymes involved in their biosynthesis are preferentially expressed in liver, the role of HNF4␣ in the regulation of bile acid production was examined. In mice, unconjugated bile acids are conjugated with taurine by the liver-specific enzymes, bile acid-CoA ligase and bile acid-CoA:amino acid N-acyltransferase (BAT). Mice lacking hepatic HNF4␣ expression exhibited markedly decreased expression of the very long chain acyl-CoA synthase-related gene (VLACSR), a mouse candidate for bile acid-CoA ligase, and BAT. This was associated with markedly elevated levels of unconjugated and glycine-conjugated bile acids in gallbladder. HNF4␣ was found to bind directly to the mouse VLACSR and BAT gene promoters, and the promoter activities were dependent on HNF4␣-binding sites and HNF4␣ expression. In conclusion, HNF4␣ plays a central role in bile acid conjugation by direct regulation of VLACSR and BAT in vivo.

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“…An ATP-dependent microsomal enzyme, bile acid-CoA synthetase (BACS), catalyzes the formation of the thioester intermediate and is considered the rate-limiting step in bile acid amidation (16). Interestingly, it was recently demonstrated that human very long chain acyl CoA synthetase homolog 2 (VLCS-H2) is a bile acid-CoA synthetase (17). VLCS-H2 belongs to a family that includes very long chain synthetase (VLCS) and fatty acid transport proteins.…”

mentioning

confidence: 99%