Identification of a novel human uridine phosphorylase.
Uridine phosphorylase catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The enzyme has an important role in the metabolism of pyrimidine analogs used in cancer chemotherapy. The cDNA of a novel 317 amino acid human uridine phosphorylase approximately 60% identical to the previously identified human uridine phosphorylase was cloned. The novel enzyme, named uridine phosphorylase-2 (UPase-2), showed broad substrate specificity and accepted uridine, deoxyuridine, and thymidine as well as the two pyrimidine nucleoside analogs 5-fluorouridine and 5-fluoro-2(')-deoxyuridine. The human UPase-2 gene was mapped to chromosome 2q24.1 and the 2.2-kb mRNA was predominantly expressed in kidney. The mouse UPase-2 cDNA was also identified and shown to be predominantly expressed in liver. The identification of a novel uridine phosphorylase with broad substrate specificity is important for studies on both nucleoside metabolism as well as for studies on the pharmacological mechanisms of therapeutic pyrimidine nucleoside analogs.
Johansson
Magnus
M
Division of Clinical Virology F68, Karolinska Institute, Huddinge University Hospital, Stockholm, S-14186, Sweden. magnus.johansson@mbb.ki.se
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013936:Thymidine / Q000378:metabolism; D014018:Tissue Distribution; D014529:Uridine / Q000737:chemistry / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D014543:Uridine Phosphorylase; C476698:uridine phosphorylase-2, human; D013936:Thymidine; D014529:Uridine