Contribution of S-adenosylhomocysteine to cardiac adenosine formation.
The S-adenosylhomocysteine (SAH) hydrolase inhibitor adenosine dialdehyde was used in isolated guinea pig hearts to determine the contribution of the transmethylation pathway to cardiac adenosine formation. This inhibitor did not alter cardiac hemodynamics but effectively inhibited SAH-hydrolase activity under in vitro and in vivo conditions. In normoxic perfused hearts adenosine dialdehyde (10 microM) caused tissue levels of SAH to linearly increase at a rate of 160 pmol/g/min over 60 min. At the same time adenosine dialdehyde decreased release of adenosine into the coronary effluent perfusate by 16 pmol/min (34%). Hypoxic perfusion (30% O2) of guinea-pig hearts increased release of adenosine from 43 to 3700 pmol/min. However, rate of SAH formation in the presence of adenosine dialdehyde was only slightly enhanced from 160 to 200 pmol/g/min and adenosine dialdehyde did not significantly alter the hypoxia induced adenosine release. Since all experiments were performed in the presence of the adenosine deaminase inhibitor EHNA (5 microM) the results demonstrate: (1) the transmethylation pathway of the heart contributes one third to global cardiac adenosine production under normoxic conditions and provides a constant source of adenosine independent of tissue oxygenation. (2) The majority of SAH-derived adenosine is salvaged most likely via adenosine kinase. (3) The hypoxia induced adenosine production is predominantly derived from enhanced 5' AMP hydrolysis.
Kentrum für Physiologie und Klin. Physiologie der Universität Düsseldorf, Federal Republic of Germany.
A
A
Deussen
H G
HG
Lloyd
J
J
Schrader
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006710:Homocysteine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007700:Kinetics; D008962:Models, Theoretical; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D012435:S-Adenosylhomocysteine / Q000378:metabolism*
D006710:Homocysteine; C027579:periodate-oxidized adenosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D012435:S-Adenosylhomocysteine; D000225:Adenine; D000241:Adenosine