HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 27, 24771-24779, July 5, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/27/24771    most recent M203295200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mihalik, S. J. Articles by Watkins, P. A. Search for Related Content PubMed PubMed Citation Articles by Mihalik, S. J. Articles by Watkins, P. A. Social Bookmarking                      What's this?

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

Stephanie J. Mihalik^§, Steven J. Steinberg^¶, Zhengtong Pei^¶, Joseph Park, Do G. Kim, Ann K. Heinzer, Georges Dacremont, Ronald J. A. Wanders^**, Dean A. Cuebas, Kirby D. Smith^§, and Paul A. Watkins^¶§§

From the  Kennedy Krieger Institute and the Departments of ^§ Pediatrics and ^¶ Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, the  Department of Pediatrics, Ghent University School of Medicine, B-9000 Ghent, Belgium, the ^** Laboratory of Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands, and the  Department of Chemistry, Southwest Missouri State University, Springfield, Missouri 65804

Bile acids are synthesized de novo in the liver from cholesterol and conjugated to glycine or taurine via a complex series of reactions involving multiple organelles. Bile acids secreted into the small intestine are efficiently reabsorbed and reutilized. Activation by thioesterification to CoA is required at two points in bile acid metabolism. First, 3,7,12-trihydroxy-5-cholestanoic acid, the 27-carbon precursor of cholic acid, must be activated to its CoA derivative before side chain cleavage via peroxisomal -oxidation. Second, reutilization of cholate and other C₂₄ bile acids requires reactivation prior to re-conjugation. We reported previously that homolog 2 of very long-chain acyl-CoA synthetase (VLCS) can activate cholate (Steinberg, S. J., Mihalik, S. J., Kim, D. G., Cuebas, D. A., and Watkins, P. A. (2000) J. Biol. Chem. 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 C₂₄ bile acids as substrates. We hypothesize that the primary function of homolog 2 is in the reactivation and recycling of C₂₄ 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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF033031.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. A. Watkins Very-long-chain Acyl-CoA Synthetases J. Biol. Chem., January 25, 2008; 283(4): 1773 - 1777. [Full Text] [PDF]

				P. A. Watkins, D. Maiguel, Z. Jia, and J. Pevsner Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome J. Lipid Res., December 1, 2007; 48(12): 2736 - 2750. [Abstract] [Full Text] [PDF]

				N. A. Styles, J. L. Falany, S. Barnes, and C. N. Falany Quantification and regulation of the subcellular distribution of bile acid coenzyme A:amino acid N-acyltransferase activity in rat liver J. Lipid Res., June 1, 2007; 48(6): 1305 - 1315. [Abstract] [Full Text] [PDF]

				S.-J. Reilly, E. M. O'Shea, U. Andersson, J. O'Byrne, S. E. H. Alexson, and M. C. Hunt A peroxisomal acyltransferase in mouse identifies a novel pathway for taurine conjugation of fatty acids FASEB J, January 1, 2007; 21(1): 99 - 107. [Abstract] [Full Text] [PDF]

				H. Doege and A. Stahl Protein-mediated Fatty Acid uptake: novel insights from in vivo models. Physiology, August 1, 2006; 21: 259 - 268. [Abstract] [Full Text] [PDF]

				Z. Pei, Z. Jia, and P. A. Watkins The Second Member of the Human and Murine "Bubblegum" Family Is a Testis- and Brainstem-specific Acyl-CoA Synthetase J. Biol. Chem., March 10, 2006; 281(10): 6632 - 6641. [Abstract] [Full Text] [PDF]

				S. Ferdinandusse, S. Denis, H. Overmars, L. Van Eeckhoudt, P. P. Van Veldhoven, M. Duran, R. J. A. Wanders, and M. Baes Developmental Changes of Bile Acid Composition and Conjugation in L- and D-Bifunctional Protein Single and Double Knockout Mice J. Biol. Chem., May 13, 2005; 280(19): 18658 - 18666. [Abstract] [Full Text] [PDF]

				C. C. DiRusso, H. Li, D. Darwis, P. A. Watkins, J. Berger, and P. N. Black Comparative Biochemical Studies of the Murine Fatty Acid Transport Proteins (FATP) Expressed in Yeast J. Biol. Chem., April 29, 2005; 280(17): 16829 - 16837. [Abstract] [Full Text] [PDF]

				Z. Pei, P. Fraisl, J. Berger, Z. Jia, S. Forss-Petter, and P. A. Watkins Mouse Very Long-chain Acyl-CoA Synthetase 3/Fatty Acid Transport Protein 3 Catalyzes Fatty Acid Activation but Not Fatty Acid Transport in MA-10 Cells J. Biol. Chem., December 24, 2004; 279(52): 54454 - 54462. [Abstract] [Full Text] [PDF]

				K. Solaas, B. F. Kase, V. Pham, K. Bamberg, M. C. Hunt, and S. E. H. Alexson Differential regulation of cytosolic and peroxisomal bile acid amidation by PPAR{alpha} activation favors the formation of unconjugated bile acids J. Lipid Res., June 1, 2004; 45(6): 1051 - 1060. [Abstract] [Full Text] [PDF]

				D. He, S. Barnes, and C. N. Falany Rat liver bile acid CoA:amino acid N-acyltransferase: expression, characterization, and peroxisomal localization J. Lipid Res., December 1, 2003; 44(12): 2242 - 2249. [Abstract] [Full Text] [PDF]

				Z. Pei, N. A. Oey, M. M. Zuidervaart, Z. Jia, Y. Li, S. J. Steinberg, K. D. Smith, and P. A. Watkins The Acyl-CoA Synthetase "Bubblegum" (Lipidosin): FURTHER CHARACTERIZATION AND ROLE IN NEURONAL FATTY ACID {beta}-OXIDATION J. Biol. Chem., November 21, 2003; 278(47): 47070 - 47078. [Abstract] [Full Text] [PDF]

				J. O'Byrne, M. C. Hunt, D. K. Rai, M. Saeki, and S. E. H. Alexson The Human Bile Acid-CoA:Amino Acid N-Acyltransferase Functions in the Conjugation of Fatty Acids to Glycine J. Biol. Chem., September 5, 2003; 278(36): 34237 - 34244. [Abstract] [Full Text] [PDF]

				T. Goto, F. Holzinger, L. R. Hagey, C. Cerre, H-T. Ton-Nu, C. D. Schteingart, J. H. Steinbach, B. L. Shneider, and A. F. Hofmann Physicochemical and physiological properties of 5{alpha}-cyprinol sulfate, the toxic bile salt of cyprinid fish J. Lipid Res., September 1, 2003; 44(9): 1643 - 1651. [Abstract] [Full Text] [PDF]

				C. N. Falany, X. Xie, J. B. Wheeler, J. Wang, M. Smith, D. He, and S. Barnes Molecular cloning and expression of rat liver bile acid CoA ligase J. Lipid Res., December 1, 2002; 43(12): 2062 - 2071. [Abstract] [Full Text] [PDF]