Modulation of phosphatidylcholine biosynthesis by peroxisome proliferating fatty acid analogues.
The modulation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) biosynthesis by sulfur-substituted fatty acid analogues has been investigated in rats. We have compared the effects of two non-beta-oxidizable fatty acid analogues, 3-thiadicarboxylic acid and tetradecylthioacetic acid, which induce proliferation of peroxisomes, with those of the analogue tetradecylthiopropionic acid, which is a weak peroxisome proliferator. Repeated administration of 3-thiadicarboxylic acid for seven days resulted in increased hepatic concentrations of both PC and PE, but the PC/PE ratio was decreased. PC synthesis was increased, as evidenced by increased incorporation of [3H]choline into PC and an increased activity of cytidinetriphosphate (CTP): phosphocholine cytidylyltransferase. This was accompanied by a reduction in the pool sizes of choline and phosphocholine. The S-adenosylmethione/S-adenosylhomocysteine ratio (AdoMet/AdoHcy) was marginally affected, indicating no increase in the rate of methylation of PE to PC. Administration of tetradecylthioacetic acid also resulted in increased hepatic phospholipid levels, increased AdoMet/AdoHcy ratios and in slightly elevated activity of CTP:phosphocholine cytidylyltransferase. The most striking effect observed after tetradecylthiopropionic acid treatment was the development of fatty liver. The activity of CTP:phosphocholine cytidylyltransferase and the incorporation of [3H]choline into PC was reduced compared to 3-thiadicarboxylic acid treatment. Although the rate of methylation of PE seemed to be increased at an elevated AdoMet/AdoHcy ratio, this resulted in only minor changes in the hepatic PC and PE levels, and the PC/PE ratio remained unchanged. Furthermore, the hepatic levels of choline and phosphocholine were reduced in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Skorve
J
J
Laboratory of Clinical Biochemistry, University of Bergen, Haukeland Sykehus, Norway.
Svardal
A M
AM
Mansoor
M A
MA
Berge
R K
RK
D000818:Animals; D003570:Cytidine Triphosphate / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*
D003998:Dicarboxylic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D013440:Sulfides; C062079:1,10-bis(carboxymethylthiodecane); D003570:Cytidine Triphosphate; C062078:1-(carboxymethylthio)tetradecane