Adenine Nucleotide Biosynthesis in Cardiac Muscle: Regulation and Intervention

摘要: It is well established that cardiac ATP breaks down when there a discrepancy between energy production and demand. This occurs in situations such as myocardial ischemia or extreme overload. In those conditions the breakdown of via ADP AMP proceeds further to adenosine, inosine hypoxanthine1. These degradation products are permeable, washed out from myocardium thus not available for restitution “salvage pathways” during recovery period. The therefore largely dependent on de novo formation (= biosynthesis) adenine nucleotides small molecular precursor substances. contrast salvage pathways, synthesis can be measured quantitatively. Utilizing 1-14C-glycine substance which rats were usually exposed 60 min, total radioactivity was related mean specific activity tissue glycine pool yielding rates nucleotide biosynthesis2. Using this approach, determined only normal rat heart but also under various pathophysiological oxygen deficiency2, hypertrophy3, stimulation with catecholamines4. all these situations, biosynthesis turned enhanced quite considerably. As far mechanisms concerned, essentially two major possibilities. 1. Regulation an ATP-dependent feedback mechanism directed at first rate-limiting enzyme biosynthesis, 5-phosphoribosyl-1-pyrophosphate amidotransferase (EC 2.4.2.14), 2. availability 5-phosphoribosyl-1-pyrophosphate.