| Abstrakt: |
The effects of D-galactosamine, D-glucosamine, and 2-deoxy-D-galactose on rat liver uracil nucleotides were studied in vivo. Enzymic and isotope dilution analyses of the UDP-sugars and of uridine phosphates revealed three major, related changes: an accumulation of the respective UDP-sugar derivatives, a marked decrease of UTP, UDP, and UMP, and a subsequent increase of the sum of hepatic uracil nucleotides. The decrease of uridine phosphates was accompanied by diminished contents of UDPG and UDP-galactose. UMP of total liver RNA was not altered significantly. Inhibition of uridylate synthesis by use of 6-azauridine resulted in a suppression of the D-galactosamine-induced stimulation of urine phosphate synthesis and of the increase in total acid soluble uracil nucleotides. The trapping of uridine phosphates by formation of UDP-sugar derivatives was most pronounced and most prolonged after administration of D-galactosamine. The urine phosphate content was lowered to less than 10% of normal within three hours, while the sum of uracil nucleotides increased by 0.35 μmole x g liver-1 xhour-1 from an initial value of 1.24 μmole/g. The qualitative analysis of the depent changes of UDP-hexosamines, YUDP-N-acetyhexosamines,UDPG and -UDP-galactose revealed a pronounced alteration by D-galactosamine of the UDP-sugar pattern. Corresponding changes in the distribution of liver uracil nucleotide were contained after administration of D-glucosamine and 2-deoxy-D-galactose. both, however, are ineffective in provoking hepatitis. in contrast to D-galactosamine, D-glucosamine and 2-deoxy-D-galactose do not lead to the formation of UDP-hexosamines; furthermore they are less efficient in trapping uridine phosphates in vivo. these observation contribute to an understanding of the orotate-mediated prevention of the galactosamine-induced liver damage, and of the role pyrimidine nucleotides in this experimental hepatitis. [ABSTRACT FROM AUTHOR] |
