Intracellular energetic units in healthy and diseased hearts.

摘要: According to the classic respiratory control theory, increased cytosolic ADP concentrations, due ATP splitting by ATPases, is an ultimate signal for cellular stimulation (1,2). The theory based on observation that when added isolated mitochondria it stimulates respiration in accordance with Michaelis-Menten kinetics and a high affinity (Km of 10 μM 20 μM) (1). However, one attempts apply living muscle vivo, several complications arise. First, concentration cells enigmatic because has never been measured directly, but instead calculated from tissue concentrations ATP, phosphocreatine (PCr) creatine determined using 31P-nuclear magnetic resonance (NMR), assumption kinase (CK) reactions are equilibrium (3–5). validity this approach questionable recent studies have revealed nonequilibrium state intracellular CK (5–8). Second, calculations yielded different results types. Glycolytic exhibits response workload, which conforms (9). heart muscle, characterized linear relationship between rate work, no significant changes ADP, PCr detected despite large variations contractile activity, condition known as metabolic stability (10–12). How then can be activated cell? Currently, there exist two concepts regarding problem. One group researchers believe transient increase cytoplasmic Ca2+ simultaneously activates apparatus mitochondria, thus matching energy demand enhanced production (13–15). This view argument both mitochondrial enzymes (dehydrogenases synthase) actomyosin complexes (13,16,17). If ‘parallel activation’ hypothesis true, transients should sufficient cause 15- 20-fold increases observed registered under conditions Frank-Starling law vivo. In fact, experimental facts disagree assumption. monitoring reveals stepwise stretch myocardium produces rapid potentiation twitch force not (16,17). When effects respiration, FoF1-ATPase membrane potential were studied was found Ca2+, although being enough participate regulation could only maximally up times, free 600 nM (18,19). It mean may extend 1 3 cardiac (20), largely exceeds levels necessary saturation Ca2+-sensitive enzymes. These data suggest vivo conditions, always proceeds close Vmax and, therefore, further accelerated Ca2+. Hence, fails explain cells. An alternative concept considers degree structural functional organization (21). states channelling means phosphotransfer systems constitutes major mechanism linking ATPases within specific structures –intracellular energetic units (ICEUs) (21–23). To date, three (CK-phosphotransfer, adenylate [AK]-phosphotransfer direct transfer adenine nucleotides) described operate ICEUs. important feature these they ensure effective oxidative phosphorylation without nucleotide contents, conferring increasing workloads. The present review summarizes support existence ICEUs pathogenic role altered metabolism diseases.