Thiophosphate‐Analogues and 1‐<i>N</i>‐Oxides of ATP and ADP in Mitochondrial Translocation and Phosphoryl‐Transfer Reactions

Abstract

1 Various thiophosphate analogues of adenine nucleotides, such as adenosine 5′-O-(1-thiotriphosphate), adenosine 5′-O-(3-thiotriphosphate), adenosine 5′-O-(1-thiodiphosphate) and adenosine 5′-O-(2-thiodiphosphate) as well as the 1-N-oxides of adenosine 5′-O-tri(and-di)-phosphates show atractyloside-sensitive (i.e. adenine nucleotide-“carrier”-linked) and insensitive (non-“carrier”-linked) binding properties to rat liver mitochondria. 2 Modified nucleoside diphosphates, such as adenosine 5′-O-(1-thiodiphosphate) and adenosine 5′-O-(2-thiodiphosphate) do not react with adenosine 5′-O-triphosphate synthetase (ATP-synthetase) in oxidative phosphorylation. Both are potent inhibitors of mitochondrial state-3 respiration whereas the 1-N-oxide of adenosine 5′-O-diphosphate does not interfere. 3 Substitution of phosphate-moiety oxygen by sulfur affects enzymatic γ-phosphoryltransfer reactions. Adenosine 5′-O-(1-thiodiphosphate) is a substrate for nucleside diphosphate kinase whereas adenosine 5′-O-(2-thiodiphosphate) is not. Adenosine 5′-O-(1-thiotriphosphate) but not adenosine 5′-O-(3-thiotriphosphate) can replace adenosine 5′-O-triphosphate in hexokinase-catalyzed glucose-phosphorylation.