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Regulation of phosphatidic acid phosphohydrolase 1 by fatty acids
Author(s) -
Elabbadi Noureddine,
Day Christopher P.,
Virden Richard,
Yeaman Stephen J.
Publication year - 2002
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-002-0865-7
Subject(s) - phosphatidic acid , lipidology , clinical chemistry , chemistry , biochemistry , fatty acid , phospholipid , membrane
In the starved state and during metabolic stress, free fatty acids (FFA) are the principal hepatic energy supply, undergoing β‐oxidation. Accordingly, it appears paradoxical that H‐A 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 β‐oxidation during times of increased energy demand.