Modeling the energy transfer pathways. creatine kinase activities and heterogeneous distribution of ADP in the perfused heart.
The exchange scheme of high energy phosphate transport in a whole heart relies on a system of CK functioning in different ways. This suggests that the CKs are able to act both like a shuttle and like a buffer for the energy transfer. The challenge is to understand how these two functions are balanced in the CK system. One key of this balance is the knowledge of the local concentrations of the ADP nucleotide. These concentrations cannot be directly measured, but they may be derived by computation. In the present report we introduce the known properties of the enzymes catalyzing the exchange of high energy phosphate into the model of flux pathways derived from NMR experiments to compute both the maximum activity of each enzyme and the local concentrations of all the substrates. We show that the ADP distribution must be heterogeneous for the system to work. Its concentration is 50% higher in the vicinity of ATPase sites and 50% lower in the intermembrane space of the mitochondria than in the cytosol. Another result of this analysis is that the apparent large unbalance of the CKmito pathway is imposed by the adenosine nucleotide transferase fluxes. This analysis proves that it is possible to deduce biochemistry the local concentrations of a substrate by combining data originating from NMR, and enzymology into a common model.
Joubert
F
F
U446 INSERM, Université Paris-Sud, Châtenay-Malabry, France.
Hoerter
J A
JA
Mazet
J L
JL
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D008433:Mathematics; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010477:Perfusion; D051381:Rats
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase