Guanine ribonucleotide metabolism in human red blood cells: evidence for a high rate of GMP dephosphorylation.
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.
Sidi
Y
Y
Department of Medicine D, Beilinson Medical Center, Petah-Tikva, Israel.
Gelvan
I
I
Brosh
S
S
Pinkhas
J
J
Sperling
O
O
D004912:Erythrocytes / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D006150:Guanine Nucleotides / Q000097:blood* / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism*; D006801:Humans; D007042:Hypoxanthines / Q000378:metabolism; D007168:IMP Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D009173:Mycophenolic Acid / Q000378:metabolism
D006150:Guanine Nucleotides; D007042:Hypoxanthines; D006147:Guanine; D006157:Guanosine Monophosphate; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid