title: Metabolism of guanine and guanine nucleotides in primary rat cardiomyocyte cultures.
abstract: The metabolic fate of labeled guanine and of prelabeled guanine nucleotides (GuRN) was studied in cultured rat cardiomyocytes. Special attention was given to guanine salvage in comparison to degradation; to the contribution of GuRN to adenine nucleotides (AdRN); to the fluxes from GMP to IMP and from IMP to GMP; and to the degradation pathways of GuRN. In accordance with the 3- to 4-fold higher activity of guanine deaminase (guanase), in comparison to that of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the rate of guanine deamination to xanthine exceeded that of guanine incorporation into nucleotides (at 4 microM) by 13.2-fold. The label from guanine incorporated into nucleotides was found mainly (81%) in GuRN, but also in IMP and AdRN. The prelabeled GuRN lost 43% of the label in 4 h, reflecting mainly degradation to xanthine (and uric acid) and synthesis of nucleic acids. Blocking nucleoside degradation was associated with a marked accumulation of label in guanosine and inosine (guanosine/inosine labeling ratio is 1.25). The results indicate that in the myocardium guanine is a poor substrate for salvage synthesis of GuRN and that its contribution to the homeostasis of adenine nucleotides is negligible; that GMP degradation to xanthine proceeds through both guanosine and IMP; and that the cardiomyocytes contain the activity of GMP reductase and of the enzymes converting IMP to GMP.
authors.affiliation: Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Zoref-Shani
authors.forename: C
authors.initials: C
authors.lastname: Shirin
authors.forename: Y
authors.initials: Y
authors.lastname: Sidi
authors.forename: Y
authors.initials: Y
authors.lastname: Bromberg
authors.forename: O
authors.initials: O
authors.lastname: Sperling
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006147:Guanine / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006150:Guanine Nucleotides; D006147:Guanine; D006157:Guanosine Monophosphate