Biosynthese von Steroidglucuroniclen durch Rattenlebermikrosomen. Zur Frage des Verhaltens der UDP-Glucuronyl-Transferase-Aktivität unter Nahrungsentzug und im Alloxandiabetes

Publisher Website
Google Scholar
Abstract
The previous concept, that rat liver microsomes, unlike those from other animal species, possess an extremely low UDP [uridine diphosphate] glucuronyl transferase activity (EC 2.4.1.17) is refuted. By the addition of the UDP-glucuronic acid pyrophosphatase inhibitors, ATP and UDP-N-acetylglucoseamine, a glucuronic acid-transferring system is obtained with a high activity towards steroids as acceptors. Microsome suspensions, which are equivalent on the basis of g fresh weight/unit volume, may possess different specific activities (nmoles testosterone glucuronide/mg protein per 30 min.) depending on the method of preparation. Under our experimental conditions, the microsome fraction catalyzes the transfer of glucuronic acid without any other changes in the steroid substrate molecule. The Michaelis constant for the synthesis of testosterone glucuronide is 8.7 x 10-5 [image]. The UDPglucuronyl transferase in rat liver microsomes shows the greatest specificity for 17[beta]-hydroxy steroids; to a small extent, 3[alpha]-hydroxy steroids can also function as acceptors for glucuronic acid. The transferase is inactive towards 3[beta]- and 21-hydroxy compounds. Unlike the hydrogenation reactions of the steroid substrate molecule, the transferase activity is the same for male and female animals. The activity of the glucuronic acid transferring enzyme during starvation and alloxan diabetes shows no significant difference from that of the controls. Thus the retarded rate of synthesis of testosterone glucuronide in intact liver cells from starved or alloxan diabetic animals is not due to a decrease in the activity of UDP glucuronyl transferase, but to a decreased availability of UDP glucuronic acid.