Abstract:
:The results of the present investigation relate the effects of the nutritional state and administration of clofibric acid (CLA), a hypolipidaemic drug and peroxisomal proliferator, on phosphatidylethanolamine (PE) synthesis in rat liver and fatty acid metabolism. Fasting and CLA treatment of animals causes an increase in the amount of PE in endoplasmic reticulum (ER) membranes and mitochondria, as well as in the PE/phosphatidylcholine (PC) ratio. Moreover, the activity of the ethanolamine-specific phospholipid base exchange (PLBE) enzyme in liver ER membranes of fasted animals was enhanced by 75% in comparison to that of animals fed ad libitum. The effect of CLA treatment was additive to that of starvation; PE synthesis tested in vitro via the Ca2+-sensitive PLBE reaction increased 3-fold in comparison to rats fed ad libitum. This is confirmed by an increased Vmax for the reaction, but the affinity of the enzyme for ethanolamine was not significantly changed. These effects were accompanied by an enhanced expression of cytochrome P450 CYP4A1 isoform and elevated activity of the enzyme upon CLA administration. The stimulatory effect of CLA administration on the efficiency of the ethanolamine-specific PLBE reaction can be explained by elimination of lauric acid, a known inhibitor of de novo PE synthesis, during the course of omega-hydroxylation catalysed by CYP4A1, and by increased expression of the PLBE enzyme. The products of omega-hydroxylation of lauric acid, which are then converted by dehydrogenase to 1,12-dodecanedioic acid, did not significantly affect the in vitro synthesis of PE.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Lenart J,Komańska I,Pikuła S,Jasińska Rdoi
10.1016/s0014-5793(98)00960-0subject
Has Abstractpub_date
1998-08-28 00:00:00pages
101-7issue
1-2eissn
0014-5793issn
1873-3468pii
S0014-5793(98)00960-0journal_volume
434pub_type
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