Distinct substrate specificity and physicochemical characterization of native human hepatic thymidine phosphorylase.

摘要: Thymidine phosphorylase (TP; EC 2.4.2.4) is involved regulation of intra- or extracellular thymidine concentration, angiogenesis, cancer chemotherapy, radiotherapy, as well tumor imaging. Although the liver main site pyrimidine metabolism and contains high levels TP, nonetheless, purification characterization human hepatic TP has not been accomplished. We here report native TP. The enzyme was purified to apparent homogeneity by a procedure shorter more efficient than previously reported methods. Human an Kthymidine 285 ± 55 μM. Like from other tissues, it highly specific 2'-deoxyribosides. However, in contrast normal active phosphorolysis 5'-deoxy-5-fluorouridine, riboside 5-fluorouridine. Furthermore, exists different aggregates 50 kDa subunits, with unknown aggregation factor(s) while extra tissues homodimer. Isoelectric point determined 4.3. A total 65 residues N-terminal were sequenced. sequence these amino acids 100% location homology deduced acid platelet derived-endothelial cell growth factor (PD-ECGF) cDNA. contrary PD-ECGF, blocked. block neither N-formyl nor pyrrolidone carboxylic moieties. differences substrate specificities, existence multimers, weak interaction hydroxyapatite resin strongly suggest that distinct extrahepatic tissues. These results may have important clinical implications when activation deactivation chemotherapeutic agents