Abstract：
:Recent experiments from our laboratory have indicated that the inhibitory effect of 3'-azido-3'-deoxythymidine (AZT) on oxidative phosphorylation may occur directly, in addition to being brought about by its inhibition of mtDNA replication. We report here studies on the effect of AZT on adenylate kinase, an enzyme crucial to oxidative phosphorylation. AZT decreased the aromatic residues fluorescence of rabbit muscle adenylate kinase, indicating binding of AZT to the enzyme. Of three other enzymes studied as controls, AZT bound only to those that possessed ATP/ADP binding sites. Up to concentrations of 15 microM, AZT was a more potent effector of fluorescence quenching than were ATP, ADP, AMP, and the AZT control, deoxythymidine. AZT strongly inhibited adenylate kinase in the direction of ATP synthesis (Ki, 8 microM), the inhibition being of the partial competitive type, whereas deoxythymidine inhibition, also partially competitive, was much weaker (Ki, 90 microM). When measured in the direction of ADP synthesis, AZT failed to demonstrate any inhibition at concentrations up to 10 microM. Experiments on isolated intact rat liver mitochondria with the enzyme activity measured in both directions confirmed the isolated enzyme results. Respiratory control by these mitochondria was not affected by AZT. The finding of AZT affinity for ATP/ADP binding sites may open new avenues of approach to the study of AZT toxicity.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Barile M,Valenti D,Hobbs GA,Abruzzese MF,Keilbaugh SA,Passarella S,Quagliariello E,Simpson MVdoi
10.1016/0006-2952(94)90564-9subject
Has Abstractpub_date
1994-10-07 00:00:00pages
1405-12issue
7eissn
0006-2952issn
1873-2968pii
0006-2952(94)90564-9journal_volume
48pub_type
杂志文章abstract：:In this study, the basis for the diminished capacity of CYP2D6.17 to metabolise CYP2D6 substrate drugs and the possible implications this might have for CYP2D6 phenotyping studies and clinical use of substrate drugs were investigated in vitro. Enzyme kinetic analyses were performed with recombinant CYP2D6.1, CYP2D6.2,...
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更新日期：1983-01-01 00:00:00
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更新日期：1985-06-15 00:00:00
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journal_title：Biochemical pharmacology
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2001-12-01 00:00:00
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journal_title：Biochemical pharmacology
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更新日期：2004-06-01 00:00:00
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journal_title：Biochemical pharmacology
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doi：10.1016/j.bcp.2012.09.006
更新日期：2012-12-01 00:00:00
