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

J. Biol. Chem., Vol. 280, Issue 19, 18658-18666, May 13, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/19/18658    most recent M414311200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferdinandusse, S. Articles by Baes, M. Search for Related Content PubMed PubMed Citation Articles by Ferdinandusse, S. Articles by Baes, M. Social Bookmarking                      What's this?

Developmental Changes of Bile Acid Composition and Conjugation in L- and D-Bifunctional Protein Single and Double Knockout Mice^*

Sacha Ferdinandusse, Simone Denis, Henk Overmars, Lisbeth Van Eeckhoudt¶, Paul P. Van Veldhoven||, Marinus Duran, Ronald J. A. Wanders, and Myriam Baes¶

From the Academic Medical Center, Laboratory of Genetic Metabolic Diseases, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands and ^¶Katholieke Universiteit Leuven, Laboratory of Clinical Chemistry, and the ^||Department of Pharmacology, 49 O/N Herestraat, Leuven B 3000, Belgium

Peroxisomal -oxidation is an essential step in bile acid synthesis, since it is required for shortening of C27-bile acid intermediates to produce mature C24-bile acids. D-Bifunctional protein (DBP) is responsible for the second and third step of this -oxidation process. However, both patients and mice with a DBP deficiency still produce C24-bile acids, although C27-intermediates accumulate. An alternative pathway for bile acid biosynthesis involving the peroxisomal L-bifunctional protein (LBP) has been proposed. We investigated the role of LBP and DBP in bile acid synthesis by analyzing bile acids in bile, liver, and plasma from LBP, DBP, and LBP:DBP double knock-out mice. Bile acid biosynthesis, estimated by the ratio of C27/C24-bile acids, was more severely affected in double knock-out mice as compared with DBP–/– mice but was normal in LBP–/– mice. Unexpectedly, trihydroxycholestanoyl-CoA oxidase was inactive in double knock-out mice due to a peroxisomal import defect, preventing us from drawing any firm conclusion about the potential role of LBP in an alternative bile acid biosynthesis pathway. Interestingly, the immature C27-bile acids in DBP and double knock-out mice remained unconjugated in juvenile mice, whereas they occurred as taurine conjugates after weaning, probably contributing to the minimal weight gain of the mice during the lactation period. This correlated with a marked induction of bile acyl-CoA:amino acid N-acyltransferase expression and enzyme activity between postnatal days 10 and 21, whereas the bile acyl-CoA synthetases increased gradually with age. The nuclear receptors hepatocyte nuclear factor-4, farnesoid X receptor, and peroxisome proliferator receptor did not appear to be involved in the up-regulation of the transferase.

Received for publication, December 20, 2004 , and in revised form, March 11, 2005.

^* This work was supported by European Community Grant QLG1-CT-2001-01277, by FWO (G.0235.01), GOA (2004/08), and NWO (916.46.109). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Laboratory of Genetic Metabolic Diseases, F0-224, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. Tel.: 31-20-5665958; Fax: 31-20-6962596; E-mail: S.Ferdinandusse{at}amc.uva.nl.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Huyghe, H. Schmalbruch, K. De Gendt, G. Verhoeven, F. Guillou, P. P. Van Veldhoven, and M. Baes Peroxisomal Multifunctional Protein 2 Is Essential for Lipid Homeostasis in Sertoli Cells and Male Fertility in Mice Endocrinology, May 1, 2006; 147(5): 2228 - 2236. [Abstract] [Full Text] [PDF]

				S. Huyghe, H. Schmalbruch, L. Hulshagen, P. V. Veldhoven, M. Baes, and D. Hartmann Peroxisomal Multifunctional Protein-2 Deficiency Causes Motor Deficits and Glial Lesions in the Adult Central Nervous System Am. J. Pathol., April 1, 2006; 168(4): 1321 - 1334. [Abstract] [Full Text] [PDF]