ABSTRACT
The flux rates through the metabolic pathways affecting the maintenance of GuRN pool in intact human RBC were studied. Normal RBC, incubated in KRBB, exhibited a markedly higher accumulation in nucleotides of Gu than of Hx. Addition of 8-AGuo, a potent inhibitor of PNP, resulted in a marked increase in the accumulation of label in the nucleosides, in Ino following incubation with Hx, and in Guo following incubation with Gu, indicating a very high rate of IMP and GMP degradation to bases through their respective nucleosides. Most of the degradation of GMP is by dephosphorylation to Guo, rather than through reductive deamination to IMP. The ultimate fate of IMP in RBC is its degradation to Ino and consequently to Hx. The contribution of AdRN or of IMP to the GuRN pool is negligible. The results indicate that concerning IMP and GMP, human RBC contain very active futile cycles, nucleotide----nucleoside----base----nucleotide, catalyzed by 5'-nucleotidase, PNP, and HGPRT. The operation of the complete cycles is essential for the maintenance of GuRN and the IMP pool size. These results may explain the finding of reduced GTP content in RBC from patients with an inborn deficiency of PNP or of HGPRT.
Subject(s)
Erythrocytes/metabolism , Guanine Nucleotides/blood , Guanine Nucleotides/metabolism , Guanosine Monophosphate/metabolism , Guanine/metabolism , Humans , Hypoxanthines/metabolism , IMP Dehydrogenase/metabolism , In Vitro Techniques , Mycophenolic Acid/metabolismSubject(s)
Erythrocytes/metabolism , Guanine Nucleotides/blood , Hypoxanthine Phosphoribosyltransferase/deficiency , Pentosyltransferases/deficiency , Purine-Nucleoside Phosphorylase/deficiency , Erythrocytes/enzymology , Guanosine Triphosphate/blood , Guanosine Triphosphate/deficiency , Humans , Hypoxanthine Phosphoribosyltransferase/blood , Purine-Nucleoside Phosphorylase/bloodABSTRACT
Autocide AMV of Myxococcus xanthus was purified and identified as phosphatidylethanolamine. Alkaline hydrolysis of AMV yielded a high proportion of mono- and diunsaturated fatty acids. The bactericidal activity of AMV on M. xanthus depended upon the density of target cells: the greater the cell density, the greater the killing by AMV. For example, at 2 U of AMV per ml, 0, 50, and 99% killing was measured with 2 X 10(4), 2 X 10(5), and 2 X 10(7) target cells per ml, respectively. The cell-density-dependent activity of AMV was also observed on solid medium. Studies with model lipid compounds suggest that the inhibitory activity of AMV is due to the fatty acid moiety, released from phosphatidylethanolamine by the concerted (enzymatic) activity of many cells. Mutants of M. xanthus selected for resistance to AMI (a mixture of fatty acids) were also resistant to AMV. The possible role of AMV in developmental lysis is discussed.
