Alterations by Clofibric Acid of Metabolism of Phosphatidylethanolamme in Rat-Liver.

Positive feedback between ethanolamine‐specific phospholipid base exchange and cytochrome P450 activities in rat liver microsomes. The effect of clofibric acid

“…Furthermore, the rate of PS decarboxylation in [3‐ 14 C]PS‐enriched mitochondria from starved animals was twice as high as in mitochondria from animals fed ad libitum (Table 2) presumably since the efficiency of PS decarboxylation depends on the efficiency of PS transport [30]. In this experiment CLA treatment resulted in the enhancement of PS decarboxylation, in agreement with results obtained by others [8]. It is worth noting that the level of PS decarboxylase activity measured in this assay was comparable to that of the ethanolamine‐specific PLBE enzyme (Fig.…”

“…The data published by other investigators [3, 5, 8]pointed to a depressed activity of enzymes (ethanolamine kinase and CTP:EP cytidylyltransferase) involved in the de novo synthesis of PE upon starvation. In our experiments (Table 2 ) the activity of ethanolamine kinase was decreased by one‐fourth upon starvation and increased by 18% after CLA administration, although not reaching the value for ad libitum fed animals.…”

“…Participation of glucagon‐stimulated PE N ‐methyltransferase cannot be excluded, since PE derived from ethanolamine is the preferred substrate for methylation to PC [40, 41]. It has been found, however, that de novo synthesis of PC in the hepatocytes of CLA‐treated rats was stimulated with the simultaneous inhibition of PE N ‐methyltransferase [7, 8]. Such fluctuations create a pool of phospholipid substrate which is used exclusively for the synthesis of PS via a calcium‐dependent serine‐specific PLBE reaction [7].…”

“…On the other hand, in rat liver after administration of clofibric acid (CLA), a correlation between the enhanced rate of phosphatidylserine (PS)‐derived PC synthesis, diminution of triacylglycerols and inhibition of PC and triacylglycerol secretion into the circulation in the form of very low density lipoproteins, has been established [7]. Interestingly, starvation and treatment with CLA resulted in an elevation of the phosphatidylethanolamine (PE) level, another representative phospholipid of eukaryotic cell membranes [5–8]. Furthermore, CLA as a xenobiotic compound induced a variety of hepatic responses, amongst them rapid proliferation of peroxisomes, smooth endoplasmic reticulum (ER) membranes and mitochondria linked to alterations in the activities of lipid‐metabolising enzymes [9–11].…”

Phosphatidylethanolamine homeostasis under conditions of impaired CDP-ethanolamine pathway or phosphatidylserine decarboxylation

“…A mechanism that could potentially increase tissue PE levels is to decrease the PEMT mediated liver conversion of PE to PC, which has been accomplished by drugs that induce peroxisome proliferation or inhibit cellular methylation (166)(167)(168)(169). Peroxisome proliferators are drugs that are known to induce the proliferation of peroxisomes, mitochondria, and ER in rodent hepatocytes (170)(171)(172)(173).…”