Guanosine monophosphate reductase 2 (GMPR2)

Guanosine monophosphate reductase 2 (GMPR2) is a human enzyme catalyzing the irreversible, NADPH-dependent reductive deamination of guanosine monophosphate (GMP) to inosine monophosphate (IMP). This process is critical in purine nucleotide metabolism, maintaining the balance between adenine and guanine nucleotides within cells. GMPR2 is structurally a homotetramer and is closely related to GMPR1, sharing much of the amino acid sequence and having similar function, though with minor differences in sequence and possibly tissue-specific roles[1][2][4][3][5]. GMPR2 operates in both nucleotide salvage and de novo synthesis pathways, influencing cellular differentiation and metabolic regulation. Altered GMPR2 function has been observed in several diseases, including Alzheimer's disease (where increased enzyme activity and downstream metabolites may exacerbate pathology via adenosine-mediated tau phosphorylation) and cancers such as melanoma (where loss of GMPR expression enhances tumor invasiveness by altering GTP availability and Rho-GTPase activity) and leukemia (where upregulation is linked to cell differentiation)[1][4]. No direct therapeutic agents targeting GMPR2 are currently clinically available, but the enzyme remains a potential metabolic target for research in neurodegeneration and malignancy.

Other names

GMP reductase 2GMPR2GMPR 2Guanosine 5'-monophosphate oxidoreductase 2hGMPR-IIGuanosine monophosphate reductase isolog

Inhibitors would block catalysis of the NADPH-dependent deamination of GMP to IMP, disrupting purine metabolic balance and potentially influencing adenosine/A1/A2 receptor-mediated pathways[1].