Role of vitamin A degradation in the control of hepatic levels in the rat.
The relationship between excess vitamin A intake and accumulation in various tissues, including the liver, was studied in rats fed for 45 d four levels of vitamin A: 1, 6, 30 and 100 IU/kcal. As vitamin A intake increased, progressively smaller fractions of the administered vitamin A were recovered in tissue. The decrease in fractional recovery in the tissues examined was calculated from the differences between intake, tissue level and excretion, and was found to increase after administration of high vitamin A diets. This could be explained, at least in part, on the basis of an enhanced rate of vitamin A degradation as a function of the increased concentration of retinol in the liver. At high tissue retinol concentrations, calculated rates of retinol metabolism via the hepatic cytosolic retinol dehydrogenase (EC 1.1.1.1) and the recently discovered microsomal retinol dehydrogenase and oxidase vastly exceeded the decrease in fractional recovery of vitamin A accumulation in the tissues. This calculated rise in metabolic rate was verified by a corresponding increase in urinary polar metabolites derived from labeled retinol. Thus, accelerated catabolism as a function of increased hepatic vitamin A concentration may provide a homeostatic mechanism which offsets in part excessive vitamin A accumulation.
Leo
M A
MA
Section of Liver Disease and Nutrition, Bronx Veterans Administration Medical Center, NY.
Kim
C I
CI
Lieber
C S
CS
D000284:Administration, Oral; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D000072467:Cytochrome P450 Family 2; D006706:Homeostasis; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology
D014801:Vitamin A; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; C504568:Cyp2d1 protein, rat; D000072467:Cytochrome P450 Family 2