Aj. Chu et Ct. Nguyen, ETHANOL INHIBITS PHOSPHATIDYLCHOLINE AND PHOSPHATIDYL-ETHANOLAMINE BIOSYNTHESIS IN HUMAN LEUKEMIC MONOCYTE-LIKE U937 CELLS, Cell biochemistry and function, 11(2), 1993, pp. 107-117
The effect of ethanol (ETOH) on the incorporation of [C-14]oleic acid
(18:1) into lipid in human monocyte-like U937 cells was investigated.
With increasing time of exposure to ETOH, the percentage of the label
distributed into neutral lipid (NL) declined from 35 per cent (3 h) to
10 per cent (24 h) accompanied by increased incorporation into phosph
olipid (PL). [C-14] 18:1 was preferentially incorporated into triglyce
ride (TG) and phosphatidylcholine (PC), comprising over 65 per cent an
d 50 per cent of the label associated with NL and PL, respectively. Lo
w concentrations of ETOH (less-than-or-equal-to 1.0 per cent; v/v) had
no effect. At concentrations greater than 1.5 per cent, there was enh
anced incorporation into TG and diacylglycerol (DAG) in a 24-h incubat
ion period, while at 16 h the label in phosphatidyl-ethanolamine (PE)
was decreased. The effect of ETOH on the CDP- choline or ethanolamine
pathway was examined by monitoring the incorporation of [H-3]choline o
r [C-14]ethanolamine into PC or PE, respectively. At low concentration
s ETOH had no effect on either choline uptake or the incorporation int
o PC. Higher concentrations (greater-than-or-equal-to 1.5 per cent) fo
r 3 and 6 h resulted in a slightly decreased choline uptake, and the r
eduction (40-50 per cent) of incorporation into PC suggests that the C
DP-choline pathway was inhibited. There was a similar inhibition of th
e incorporation of [C-14]ethanolamine into PE. When the cells were inc
ubated for 3 h in the presence of 2 per cent ETOH and with labelled 18
: 1 and PL-base, the ratios of incorporation (base/18:1) into PC and P
E fractions decreased, indicating that the major inhibition lay in blo
ckage of the availability of the base moiety for PL formation. Analysi
s of the distribution of the label into metabolites revealed that ETOH
inhibited the conversion of [C-14] ethanolamine into [C-14]phosphoryl
ethanolamine. The reduction in incorporation was not due to the enhanc
ed breakdown of base-labelled PL. Our results indicate that ETOH has a
n inhibitory effect on the CDP-choline or ethanolamine pathway.