On the formation of uric acid by hepatic xanthinedehydrogenase

Abstract

An excessive concentration of xanthi­ nedehydrogenase substrates, such as xanthine or hypoxanthine, inhibits in 1)1170 the activity of the chicken liver enzyine. This phenomenon first appears when the substrate level is above 1 x io-'1 M, but increases considerably with higher concentrations of the base. The reversibility of the inhibition has been proved either by removal of the purines by dialysis, or simply by diluting the Solutions.

When 5 x 10-4 M hypoxanthine is introduced into a 5 x io“4 M xanthine-xanthinedehydrogenase system, a decrease of about 40 % in the normal uric acid production is observed, provided a short period of incubation time — 20 minu­ tes — is taken into consideration : a certain amount of xanthine accumulates then in the médium, the result of an initial dehydrogenation of hypoxanthine. Tlowever, if the incubation period is longer — 60 minutes— the xanthine level tends to decrease and a correspondingly greater uric acid formation takes place.

Adenine appears to inhibit the enzymatic conversión of xanthine into uric acid, the action being of a competitivo character. Adenine itself is converted into uric acid by liver homogenates, but when the substrate concentration exceeds 1 x 10-4 M, a decrease in the uric acid formation is observed. Adenosine, inosine and uric acid, do not seem to interfere with the enzymatic dehydrogena­tion of xanthine. On the other hand, 5 x 10-3 M histamine inhibits the activity of the xanthinedehydrogenase.

These observations, we believe, may contribute to an interpretation of the physiological regulation of the uric acid production that takes place in the hepa­tic gland in siiu.