Purine utilisation, de novo synthesis and degradation in mouse preimplantation embryos Available to Purchase

The importance of de novo purine synthesis as opposed to the réutilisation of metabolites by salvage pathways, and the nature of the excretory product(s) of purine degradation, have been examined in cultured pre-implantation mouse embryos. In the presence of azaser-ine and mycophenolic acid, which inhibit de novo purine synthesis, embryo cleavage was blocked prior to com-paction, the precise stages at which this occurred depended on whether the cultures were established on day 1 or day 2 after fertilisation, and indicated that salvage pathways were insufficient to fulfil the demand for nucleotides during early preimplantation develop-ment. The end-product of purine degradation appeared to be xanthine, which was excreted in very small amounts on days 1, 2 and 3, with a pronounced rise from the early to late blastocyst. Uric acid formation or excretion could not be detected. Exogenous hypoxan-thine and adenine, which partially inhibited develop-ment, were taken up by the embryos and converted to xanthine, most probably by salvage pathways, since the enzyme xanthine oxidase, which converts hypoxanthine directly to xanthine and then to uric acid, could not be detected. Exogenous guanine bad little effect on develop-ment and was also converted to xanthine, but in this case, the conversion was probably in a single step, via the enzyme guan ase.