Evidence of a new phosphoryl transfer system in nucleotide metabolism.
Crude rat liver extract showed AMP-AMP phosphotransferase activity which, on purification, was ascribed to a novel interaction between adenylate kinase, also known as myokinase (EC 2.7.4.3), and adenosine kinase (EC 2.7.1.20). The activity was duplicated using the same enzymes purified from recombinant sources. The reaction requires physical contact between myokinase and adenosine kinase, and the net reaction is aided by the presence of adenosine deaminase (EC 3.5.4.4), which fills the gap in the energy balance of the phosphoryl transfer and shifts the equilibrium towards ADP and inosine synthesis. The proposed mechanism involves the association of adenosine kinase and myokinase through non-covalent, transient interactions that induce slight conformational changes in the active site of myokinase, bringing two already bound molecules of AMP together for phosphoryl transfer to form ADP. The proposed mechanism suggests a physiological role for the enzymes and for the AMP-AMP phosphotransferase reaction under conditions of extreme energy drain (such as hypoxia or temporary anoxia, as in cancer tissues) when the enzymes cannot display their conventional activity because of substrate deficiency.
Vannoni
Daniela
D
Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Italy.
Leoncini
Roberto
R
Giglioni
Stefania
S
Niccolai
Neri
N
Spiga
Ottavia
O
Aceto
Emilia
E
Marinello
Enrico
E
D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D030342:Genetic Diseases, Inborn / Q000201:enzymology / Q000235:genetics; D006402:Hematologic Diseases / Q000201:enzymology / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D009711:Nucleotides / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D009711:Nucleotides; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D000263:Adenylate Kinase; D000241:Adenosine