Studies on metabolism of vitamin A. Absorption of retinal (vitamin A aldehyde) in rats

1. Young rats with low reserves of vitamin A were dosed with retinal in groundnut oil, and the stomach, the contents, mucosa and muscles of small intestine, the blood and the liver were analysed at periods up to 24hr. after dosing. 2. Up to 6hr. after the dose, retinal was present in high concentrations in the contents, mucosa and muscles of the intestine. Small but significant amounts were present in blood and liver at all times. 3. The intestinal mucosa and muscles always contained small amounts of retinol and its esters. 4. A study of the distribution of the three forms of the vitamin within the mucosal cell showed that most of the mucosal retinal enters the cell unchanged. 5. When protein-depleted rats were similarly given retinal, the rate of reduction of the aldehyde, and the consequent deposition in the liver of retinol and its esters, progressively decreased with reduced protein intake.     

Studies on metabolism of vitamin A. The effect of the stage of vitamin A deficiency on sulphate activation in rat liver

1. The synthesis of ;active sulphate' in rat liver was studied at various stages of vitamin A deficiency, with the corresponding pair-fed controls. 2. The activity was significantly decreased even at the onset of the deficiency, and at the acute stage there was further loss. 3. Only at the earlier stages of the deficiency was the addition of retinol, in vitro, fully effective in restoring the lost activity; retinoic acid was partially active. No such restoration was possible at the acute deficiency stage.     

Studies on metabolism of vitamin A. The effect of vitamin A status on the secretion rates of some steroids into the ovarianvenous blood of pregnant rats

1. Rats raised on a vitamin A-deficient diet supplemented with either retinyl acetate or retinoic acid were mated and became pregnant. 2. The rates of secretion of progesterone, 20alpha-hydroxypregn-4-en-3-one, oestradiol-17beta and oestrone into the ovarian-venous blood of rats in these two groups were measured on days 9 and 15 of pregnancy. 3. Rates of secretion of progesterone and 20alpha-hydroxypregn-4-en-3-one, both on days 9 and 15, were lower for the rats given retinoic acid. No such differences were found in ovarian oestrogen secretion. 4. The implications of these results are discussed in the light of the previous demonstration that the activity of ovarian 3beta-hydroxy-Delta(5)-steroid dehydrogenase was markedly less in pregnant rats given retinoic acid.     

The effects of vitamin A deficiency on hepatic folate metabolism in rats

The effects of severe vitamin A deficiency (liver retinol less than 2 micrograms/g) on hepatic folate metabolism in rats were studied. The oxidation of a [ring-2-14C] histidine load or a [14C]formate load to 14CO2 was significantly depressed in vitamin A-deficient rats and those given histidine also excreted more urinary formiminoglutamic acid (FiGlu) than pair-fed controls. The increase in FiGlu excretion was not due to augmented production from histidine, implicating an impairment of FiGlu catabolism. FiGlu formiminotransferase activity was unaltered in vitamin A-deficient rats, but hepatic tetrahydrofolic acid (THF) concentration was decreased by 58% in vitamin A-deficient rats given a histidine load while 5-methyl-THF concentration was increased by 39%. Formyl-THF and total folate levels were similar to controls. A redistribution of folate coenzymes was not found in vitamin A-deficient rats not force fed histidine. A 43% decrease in 10-formyl-THF dehydrogenase activity, which generates both THF and the 14CO2 from the labeled substrates, and an 81% increase in 5,10-methylene-THF reductase activity, which generates 5-methyl-THF, were found in vitamin A-deficient rats. It appears that the production of severe vitamin A deficiency results in selective changes in the activities of hepatic folate-dependent enzymes, so that when a load of a one-carbon donor is given, THF concentration decreases and metabolism of the load is impaired.