Modulation of phosphatidylcholine biosynthesis by peroxisome proliferating fatty acid analogues.

Abstract

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)

• Authors: J Skorve, A M Svardal, M A Mansoor, R K Berge
• Journal: Lipids (Lipids) Vol. 28 Issue 9 Pg. 795-801 (Sep 1993) ISSN: 0024-4201 [Print] United States
• PMID: 8231655 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dicarboxylic Acids
• Phosphatidylcholines
• Phosphatidylethanolamines
• Phospholipids
• Sulfides
• 1,10-bis(carboxymethylthiodecane)
• Cytidine Triphosphate
• 1-(carboxymethylthio)tetradecane

Topics

• Animals
• Cytidine Triphosphate (metabolism)
• Dicarboxylic Acids (pharmacology)
• Liver (metabolism)
• Male
• Microbodies (drug effects, metabolism)
• Phosphatidylcholines (biosynthesis)
• Phosphatidylethanolamines (biosynthesis)
• Phospholipids (analysis)
• Rats
• Rats, Wistar
• Sulfides (pharmacology)