Choline oxidation and labile methyl groups in normal and choline-deficient rat liver

Abstract

1. 1. The metabolism of choline as a methyl group donor, via oxidation to betaine, has been studied in normal rats and rats in the early stages of choline deficiency. 2. 2. Liver triglyceride levels increased 4-fold in 2 days, 20-fold in 6 days and 40-fold in 13 days on a choline-deficient diet. In contrast, free fatty acid levels were low and did not increase significantly until between the 6th and 13th day. 3. 3. The level of free choline in liver was low in normal rats (1.1 μmoles/100 g body wt.) and was reduced by about 50% in 2-day deficient animals. High levels of betaine were found in normal liver (24.5 μmoles/100 g body wt.) but in the deficient animals the betaine pool was too low to be measured. 4. 4. The radioactivity from [1,2- 14C 2]choline, injected intraperitoneally, appearing in phosphorylcholine and betaine was very much less in the livers of 2-day-choline-deficient rats as compared with controls, suggesting a reduced conversion of choline to these derivatives. 5. 5. In vitro measurements of choline oxidase and betaine aldehyde dehydrogenase in whole homogenates, mitochondria and cell supernatant revealed no significant reduction in the activities of these enzymes at two days of deficiency although there was some reduction at later stages. Inhibition of choline oxidase in vitro by free fatty acids was demonstrated, but these findings do not seem to be relevant to the depletion of the betaine pool and the apparent reduction in conversion of [1,2- 14C 2]choline to betaine in vivo since the free fatty acid levels were essentially unaltered in the choline-deficient animals. 6. 6. There was a trend towards a decrease in the level of free methionine but a suggested increase in S-adenosylmethionine in livers at 2 and 6 days of deficiency, although the changes were not statistically significant. Thus, there was no obvious evidence of a methyl group deficiency in the choline-deficient animals.