Regulation of phosphatidic acid phosphohydrolase 1 by fatty acids

被引：8

作者：

Elabbadi, N

Day, CP

Virden, R

Yeaman, SJ ^{[1
]}

机构：

[1] Univ Newcastle Upon Tyne, Sch Biochem & Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Univ Newcastle Upon Tyne, Sch Med, Liver Res Ctr, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

来源：

LIPIDS | 2002年 / 37卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1007/s11745-002-0865-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the starved state and during metabolic stress, free fatty acids (FFA) are the principal hepatic energy supply, undergoing beta-oxidation. Accordingly, it appears paradoxical that FFA have been reported to increase the liver's esterification capacity by translocating the rate-limiting enzyme phosphatidic acid phosphohydrolase (PAP-1) from the cytosol to the endoplasmic reticulum. We have therefore investigated the regulation of rat liver PAP-1. Oleic acid inhibited PAP activity in all subcellular fractions, with PAP-1 activity in cytosol being the most sensitive. Inhibition was also observed with oleoyl-CoA, linoleate, and palmitate. Fatty acids and their derivatives show detergent effects at high concentrations, and such effects can lead to enzyme inhibition. Inhibition by oleate, however, was reversed by phosphatidic acid and albumin and exhibited sigmoidal kinetics. These results demonstrate that PAP-1 is reversibly inhibited by FFA and their CoA esters, which may play a role in directing hepatic FFA to beta-oxidation during times of increased energy demand.

引用

页码：69 / 73

页数：5

共 27 条

[1] RELATIONSHIP BETWEEN TRANSLOCATION OF LONG-CHAIN ACYL-COA HYDROLASE, PHOSPHATIDATE PHOSPHOHYDROLASE AND CTP - PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE AND THE SYNTHESIS OF TRIGLYCERIDES AND PHOSPHATIDYLCHOLINE IN RAT-LIVER [J].