Control analysis of biliary lipid secretion

Journal of Theoretical Biology
A K GroenJ M Tager

Abstract

Biliary lipid secretion is a complex process involving a multitude of metabolic pathways. It has always been assumed that bile salt secretion (BSec) fully controls this process. Recently we have demonstrated, that mdr2 P-glycoprotein (P-gp) is an important controlling step as well. In this study we have analysed the control structure of this pathway with Metabolic Control Analysis. FVB mice homozygous (+/+) or heterozygous (+/-) for mdr2 P-glycoprotein were infused via the tail vein with tauroursodeoxycholate in stepwise increasing concentrations. Bile was collected and biliary lipids were determined by standard techniques. To simplify the pathway we have lumped all reactions involved in BSsec into bile in one step. Since this step is not controlled by the canalicular BS concentration, the FCC of BS secretion on phospholipid secretion (PLsec) could be calculated from a plot between BS and PL secretion. The FCC of BSsec varied from 80% at low flux to a value of 90% at maximal BS output. The FCC of mdr2 P-gp was determined by varying the gene dose of mdr2 P-gp. Since PLsec showed linear kinetics towards canalicular BS the FCC could be calculated via the Deviation index. The values for the FCC of mdr2 P-gp in (+/+) mice vary from ...Continue Reading

Citations

Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A J SmithP Borst
Jan 22, 1998·Mammalian Genome : Official Journal of the International Mammalian Genome Society·F LammertD R Beier
Oct 27, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Erwin GeukenRobert J Porte

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