Disease relevance of GMPR

• In vitro translation in the rabbit reticulocyte system and transient expression in Cos7 cells were performed to characterize the protein encoded by a chromosome 6-linked human cDNA clone, whose nucleotide sequence is homologous to that of Escherichia coli guanosine monophosphate reductase (GMP reductase) cDNA [1].

High impact information on GMPR

• The human mRNA that provides the N-terminus of chimeric G6PD encodes GMP reductase [2].
• We speculate that the physiological function of the marked increase in BAT GMP-r during cold stress may be to deplete the brown adipocyte of guanine nucleotides, converting them to IMP, thus permitting enhanced UCP-1 function [3].
• The first is the inhibition of GMP reductase by the IMP analogues allopurinol ribonucleoside monophosphate and thipurinol ribonucleoside monophosphate which reduces the organism's ability to synthesize ATP from guanine [4].
• Structure comparison and sequence alignment analyses show that the conformation of the active site loop (residues 179-187) is similar to those of hGMPR1 and inosine monophosphate dehydrogenases (IMPDHs) [5].
• NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties [6].

Biological context of GMPR

• Human GMP reductase has been previously partially purified from erythrocytes and a chromosome 6-linked cDNA has been identified to correspond for encoding human GMP reductase [6].
• The activity of GMP reductase showed no linkage with neoplastic or normal cell proliferation; however, in induced differentiation in HL-60 cells the activity increased concurrently with the decline in the activity of IMPDH [7].
• Steady-state kinetics of the reaction catalyzed by GMP reductase [8].

Anatomical context of GMPR

• Treatment of HL-60 cells with retinoic acid (1 microM) induced granulocytic differentiation which was accompanied with a 2.4-fold increase in GMPR and 55% decrease in IMPDH activities [9].
• This is the first report suggesting the existence of two distinct types of human GMP reductase molecular species, which can be used to explain the bimodal saturation curve noted with the purified human erythrocyte GMP reductase [6].

Associations of GMPR with chemical compounds

• Incubation with guanosine (200 microM), which expands the guanine nucleotide pool, elevated GMPR (1.9-fold) and decreased IMPDH (73%) activities [9].
• The synchronous and opposing alterations in GMPR and IMPDH activities should amplify the metabolic response due to differentiation or guanylate pool expansion [9].
• Monophosphates of formycin B and allopurinol riboside. Interactions with leishmanial and mammalian succino-AMP synthetase and GMP reductase [10].
• Metabolic studies indicated decreased synthesis of DNA, variable inhibition of de novo purine synthesis, and complete inhibition of the enzyme guanosine monophosphate reductase by 3-deazaguanosine [11].

Other interactions of GMPR

• Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells [12].

Analytical, diagnostic and therapeutic context of GMPR

• Mapping of the human guanosine monophosphate reductase gene (GMPR) to chromosome 6p23 by fluorescence in situ hybridization [13].
• These investigations should contribute to the clarification of the controlling factors of GMP biosynthesis, the role of the various enzymes, the behavior of GMP reductase in mammalian cells and the application of the approaches of enzyme-pattern-targeted chemotherapy in patients [7].

References