In:
Lipids, Wiley, Vol. 28, No. 9 ( 1993-09), p. 795-801
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‐β‐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 [ 3 H]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 [ 3 H]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. The activities of the two enzymes competing for choline in the liver, choline kinase and choline dehydrogenase were changed in opposite directions, with the activity of choline kinase increasing approximately 1.5‐fold. In addition, it was found that the level of homocysteine was elevated in the liver of tetradecylthiopropionic acid‐treated rats. The possibility is discussed that this reflects a reduced flux of choline through the oxidative pathway in the liver. In tetradecylthiopropionic acid‐treated rats, there seemed to be a coordinated regulation of the two pathways for PC biosynthesis, with an increase in the methylation of PE to PC and a reduced synthesis via the CDPcholine pathway. The increase in PC observed in rats treated with 3‐thiadicarboxylic acid and tetradecylthioacetic acid suggests that increased PC synthesis is linked to peroxisome proliferation.
Type of Medium:
Online Resource
ISSN:
0024-4201
,
1558-9307
Language:
English
Publisher:
Wiley
Publication Date:
1993
detail.hit.zdb_id:
2030265-4
SSG:
12
Permalink
