Role of vitamin A in sulphate metabolism: Studies on the enzymic activation of sulphate by various tissue extracts of normal and vitamin A-deficient rats

1. The enzymic activation of sulphate by various tissue extracts of vitamin A-deficient rats and their pair-fed controls was studied. 2. Vitamin A deficiency does not impair the enzymic activity in liver, colon and brain. However, a significant decrease in activity was observed in epiphyseal cartilage.     

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.     

Impaired biliary secretion of immunoglobulin A in vitamin A-deficient rats

The effect of vitamin A deficiency on biliary secretion of IgA was investigated. Rats used in this study were rendered vitamin A deficient following withdrawal of retinoic acid from the diet of retinoate-cycled animals. This procedure allows a precise control of both the onset of deficiency and dietary protein-energy input. Defective synthesis and transport of IgA antibodies into the bile was evident when vitamin A-deficient rats (A-) were immunized by injections of either Brucella abortus or sheep red blood cells directly into the Peyer's patches. Antibody titers in the bile of A- animals were significantly lower than those of A+ controls (P less than 0.01). These A- rats also had significantly lower levels of total IgA in the bile compared with A+ controls (P less than 0.05). Moreover, the transport of labeled rat IgA injected intravenously was adversely affected in these animals. These results, together with our previous report on the impaired intestinal antibody in A- rats, clearly indicate that vitamin A deficiency interferes with the transport of IgA antibodies into the bile of these animals.     

The effect of molybdenum on ascorbic acid metabolism in rats

1. The effect of dietary molybdenum on the growth rate and also on ascorbic acid metabolism in rats was studied. An excess of dietary molybdenum resulted in growth retardation and loss of weight. Tolerance to molybdenum was affected by the nature of the molybdenum salt administered. 2. Molybdenum ingestion altered certain aspects of ascorbic acid metabolism in rats. The conversion of d-glucuronolactone into l-ascorbic acid in vitro and the oxidative breakdown of l-ascorbic acid by liver enzymes decreased with high molybdenum intakes. The activity of liver uronolactonase was slightly inhibited. The activities of l-gulonate dehydrogenase and l-gulonate decarboxylase were not affected appreciably. 3. Molybdenum supplementation of the control diet resulted in an increase in ascorbic acid content of spleen and adrenal gland, and in a marked decrease in the urinary excretion of ascorbic acid and glucuronic acid. The implications of these findings are discussed.     

Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats

Ascorbic acid (AA) metabolism in streptozotocin (STZ)-induced diabetic rats was determined by examining urinary excretion, renal reabsorption, reductive regeneration, and biosynthesis of AA at 3 and 14 days after STZ administration. AA concentrations in the plasma, liver, and kidney of the diabetic rats were significantly lower than those of controls on d 3, and decreased further as the diabetic state continued. Hepatic AA regeneration significantly decreased in the diabetic rats on d 3 in spite of increased gene expressions of AA regenerating enzymes and was further reduced on d 14. Hepatic activity of L-gulono-gamma-lactone oxidase, a terminal enzyme of hepatic AA biosynthesis, also decreased significantly on d 3 and decreased further on d 14. Urinary excretion of AA was significantly increased on d 3, with an increase in urine volume but no change in gene expressions of renal AA transporters (SVCT1 and SVCT2). Urinary excretion of AA was normalized on d 14. The results suggest that impaired hepatic and renal regeneration, as well as increased urinary excretion and impaired hepatic biosynthesis of AA, contributed to the decrease in AA in plasma and tissues of STZ-induced diabetic rats.     

Glutathione and ascorbic acid metabolism and antioxidant enzyme activity in the tissues of vitamin E-deficient rats

In has been shown in the experiments on male rats that alimentary vitamin E deficit causes the decrease of reduced glutathione and ascorbic acid concentration in the liver and lungs and that of glutathione-S-transferase, glutathione reductase in the liver and lungs, catalase in the liver and glutathione peroxidase in the heart activity, but increases the amount of glutathione disulfide in the liver and lungs and superoxide dismutase and gamma-glutamyltransferase activity in the liver. The data obtained show the selective character of reaction participants of the antioxidant system of rats' organism to the deficit of one of the antioxidant factors--vitamin E and also testify to complex interrelation between separate members of this system.     

The influence of dietary protein on ascorbic acid metabolism in rats

1. d-Glucuronolactone reductase, l-gulonolactone oxidase, uronolactonase, dehydroascorbatase, l-gulonate dehydrogenase and l-gulonate decarboxylase have been measured in the tissues of rats fed on diets containing variable amounts of protein. Rats fed on a protein-free or a 2% casein diet for 15 days showed a marked decline in the activities of d-glucuronolactone reductase, l-gulonolactone oxidase, uronolactonase and dehydroascorbatase in the liver, and no change in l-gulonate dehydrogenase and l-gulonate decarboxylase activities in the kidney when compared with rats fed on diets containing 9%, 18% or 25% casein. Giving diets containing 60% or 88% casein to rats did not appreciably alter the activities of uronolactonase, dehydroascorbatase, l-gulonate dehydrogenase and l-gulonate decarboxylase, but inhibited considerably the activities of d-glucuronolactone reductase and l-gulonolactone oxidase in the liver, resulting in decreased synthesis of ascorbic acid. 2. Rats fed on a 25% casein diet showed maximal weight gain, higher tissue reserve of ascorbic acid and higher urinary excretion of both ascorbic acid and glucuronic acid when compared with rats fed on diets containing lower or higher amounts of protein.     

Effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice

The effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice has been studied. After the mice were on diets containing added ascorbic acid for two months, the activities of ascorbic acid synthesizing enzymes in the mouse liver homogenates were measured using L-gulono-gamma-lactone as a substrate. Exogenous ascorbic acid intake (0.5, 1 or 5% in the diet) was able to increase the concentration of ascorbic acid in the blood and to decrease the activities of ascorbic acid synthesizing enzymes in mouse liver. The results suggest that ascorbic acid synthesis was controlled by local regulatory mechanism or by the concentration of ascorbic acid in the hepatic portal blood. Ingestion of dietary erythorbic acid, a stereoisomer of ascorbic acid, had no effect on the activities of ascorbic acid synthesizing enzymes.