Metabolic fate of arachidonic acid in hepatocytes of continuously endotoxemic rats.
The present experiments were designed to characterize the kinetics of [1-14C]arachidonic acid (AA) metabolism as a function of time in hepatocytes obtained from rats infused continuously for 30 h with a nonlethal dose of Escherichia coli endotoxin (ET). Chronic endotoxemia greatly reduces the ability of hepatocytes to utilize [1-14C]AA, which is reflected from the earliest times of incubation in very low labeling of intermediates in the biosynthetic pathways of glycerolipids (phosphatidic acid and diacylglycerol) and slower removal of [1-14C]AA from the free fatty acid pool as compared with saline-infused rats. At later times of incubation, the labeling of phospholipids (especially phosphatidylethanolamine and phosphatidylinositol [PI]), but not of triacylglycerides is decreased. Analysis of fatty acid composition of individual phospholipids from cells of ET-infused rats reveals that the content of AA is significantly reduced only in PI. Hence an impairment in activation/acylation enzymatic mechanisms could affect the turnover of metabolically active phospholipid pools, i.e., PI, involved in signal transmission processes, and result in increased availability of 20:4 for eicosanoid synthesis, contributing to cellular metabolic perturbations in endotoxicosis.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002908:Chronic Disease; D004731:Endotoxins / Q000008:administration & dosage; D004927:Escherichia coli Infections / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism*
D001095:Arachidonic Acids; D004731:Endotoxins; D005227:Fatty Acids; D010743:Phospholipids; D016718:Arachidonic Acid