METABOLISM OF GUANINE AND GUANINE-NUCLEOTIDES IN PRIMARY RAT CARDIOMYOCYTE CULTURES

The metabolic fate of labeled guanine and of prelabeled guanine nucleo tides (GuRN) was studied in cultured rat cardiomyocytes. Special atten tion was given to guanine salvage in comparison to degradation; to the contribution of GuRN to adenine nucleotides (AdRN); to the fluxes fro m GMP to IMP and from IMP to GMP; and to the degradation pathways of G uRN. In accordance with the 3- to 4-fold higher activity of guanine de aminase (guanase), in comparison to that of hypoxanthine-guanine phosp horibosyltransferase (HGPRT), the rate of guanine deamination to xanth ine exceeded that of guanine incorporation into nucleotides (at 4 mu M ) by 13.2-fold. The label from guanine incorporated into nucleotides w as found mainly (81%) in GuRN, but also in IMP and AdRN. The prelabele d GuRN lost 43% of the label in 4 h, reflecting mainly degradation to xanthine (and uric acid) and synthesis of nucleic acids. Blocking nucl eoside degradation was associated with a marked accumulation of label in guanosine sine and inosine (guanosine/inosine labeling ratio is 1.2 5). The results indicate that in the myocardium guanine is a poor subs trate for salvage synthesis of GuRN and that its contribution to the h omeostasis of adenine nucleotides is negligible; that GMP degradation to xanthine proceeds through both guanosine and LMP; and that the card iomyocytes contain the activity of GMP reductase and of the enzymes co nverting IMP to GMP. (C) 1995 Academic Press, Inc.