Studies on the transacylation of retinol catalyzed by acyl coenzyme A:retinol O-acyltransferase

• Main Author: Ball, Mark David
• Format: Text
• Language: English
• Published: Iowa State University Digital Repository 1987
• Subjects: Biochemistry and biophysics; Biochemistry; polar bear
• Online Access: https://lib.dr.iastate.edu/rtd/8615; https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=9614&context=rtd

Acyl coenzyme A:retinol O-acyltransferase (ARAT), a microsomal enzyme, is thought to catalyze the transacylation reaction whereby retinol is esterified in vivo. Therefore, by means of an in-vitro assay method measuring net synthesis of retinyl esters, properties of the enzyme in various tissues were studied;ARAT was characterized in the liver of a polar bear, a species with exceptionally large vitamin-A reserves. The activity observed was unusually high. Vitamin A was present in the liver at 8050 [mu]g/g tissue, with 98% of the vitamin in its ester form. However, the activity of ARAT in rat mammary tumor, a tissue in which retinyl esters do not accumulate, was very low. Furthermore, administration of vitamin A to the animals enhanced ARAT activity in both tumor and liver. Thus, ARAT may have a physiological role in the esterification of retinol in vivo;ARAT was inhibited in vitro by various retinoids, including 13-cis-retinoic acid, a drug used at high doses in the treatment of recalcitrant acne. However, the drug not only inhibited benzo(a)pyrene hydroxylation also, but it increased the permeability of the microsomes to mannose-6-phosphate, as evidenced by a rise in mannose-6-phosphatase activity. Therefore, retinoids that inhibit ARAT in vitro should also be tested on other membrane-bound enzyme systems. Inasmuch as four other amphiphiles were much less effective at increasing membrane permeability to mannose-6-phosphate in vitro, 13-cis-retinoic acid may act in vivo, at least in part, by disrupting membranes;CoA thioesters of oleic and C[subscript]12-C[subscript]20 saturated fatty acids were effective substrates for rat-liver ARAT in vitro, whereas polyunsaturated derivatives were virtually ineffective. ARAT from polar-bear liver displayed a similar specificity. However, ARAT specificity observed in vitro fails to account for the fatty-acid composition of retinyl esters in vivo, inasmuch as retinol exists in the liver mainly as the palmitate ester, with lesser amounts of retinyl stearate and oleate. Thus, a second retinol-acylating enzyme may exist in the liver, working in conjunction with ARAT.