Uridine phosphorylase from Hymenolepis diminuta [Cestoda]: Kinetics and ihibition by pyrimidine nucleoside analogs

• Autorzy: Drabikowska A. K.
• Języki publikacji: EN

Abstrakty

EN

A single pyrimidine nucleoside phosphorylase was found in the cytoplasmic extract from Hymenolepis diminuta. This enzyme preferentially cleaves uridine and, to a much lesser extent, thymidine. Its presence directly indicates the existence of pyrimidine nucleoside salvage pathway in this parasite. Detailed kinetic studies in the phosphorolytic and synthetic direction pointed to the sequential mechanism of these reactions. For phosphorolysis, Kurd = 33 ^M and Kp = 806 nM. For synthesis of uridine, KUra = 204 jiM and Ki.p.rib.= 50 pM. Over six times higher Km for uracil than for uridine indicates that phosphorolysis is the favoured reaction in this tapeworm. Well known inhibitors of mammalian uridine phosphorylase: 2,2'-anhydro-5- -ethyluridine and l-(l,3-dihydroxy-2-propoxymethyl)-5-benzyluracil (DHPBU), both with Ki = 0.07 nM were potent competitive inhibitors of the enzyme from H. diminuta. The newly synthesized 2,3'-anhydro-5-ethyluridine (K. Felczak,unpublished) showed only moderate inhibitory activity (Ki = 14 jiM) similarly as l-(l,3-dihydroxy-2- -propoxy-methyl)-5-benzyluracil. The same order of Ki values obtained for the investigated inhibitors vs uridine phosphorylase, irrespective whether the enzyme was isolated from rat intestinal mucosa (Drabikowska etal., 1987,Biochem. Pharmacol. 36,4125-4128) or H. diminuta may point to a great similarity between binding sites on the parasite and the host enzyme.

Słowa kluczowe

EN

pyrimidine nucleoside; Cestoda; Hymenolepis diminuta; uridine phosphorylase; thymidine; kinetics; inhibitor

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1996
• Tom: 43
• Numer: 4
• Opis fizyczny: p.733-741,fig.

Twórcy

autor

Drabikowska A. K.

• Polish Academy of Sciences, A.Pawinskiego 5a, 02-106 Warsaw, Poland

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