r-Galactonolactone in experimental galactosemic animals.
An accumulation of galactose-1,4-lactone, an oxidation product of galactose, was observed in various tissues of galactosemic guinea pigs fed a 40% galactose diet for 6 weeks. In addition, an accumulation of the two galactose metabolites varied among organs. The highest content of the lactone was observed in the liver and the content of the lactone exceeded that of the reduced counterpart. The lens gave the highest galactitol content. In the serum the level of the lactone was very low. A trace amount of the lactone was detected in the kidney while it was mostly excreted into urine within 54 h upon withdrawal of the diet. On the other hand, in the animals kept on a high galactose diet for only 2 days, urinary lactone rapidly decreased. These observations indicated that a high galactose level in the circulation was associated with the production of the lactone in various tissues and that the accumulated lactone was released into the circulation very slowly and then excreted into the urine. Suppression of galactitol production by administration of an aldose reductase inhibitor resulted in the accumulation of the lactone in the lens, the testis, and the muscle, as well as in the circulation. The lactone thus produced was excreted exclusively into the urine. This observation indicates a close relationship between the oxidative and reductive metabolisms of galactose at a toxic level.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D005690:Galactose / Q000378:metabolism*; D005693:Galactosemias / Q000378:metabolism*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007783:Lactones / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D010084:Oxidation-Reduction; D014018:Tissue Distribution
D007093:Imidazoles; D048289:Imidazolidines; D007783:Lactones; C037070:M 79175; D000449:Aldehyde Reductase; D005690:Galactose