Prediction of the resistance to hypoxia on the basis of modifications of the adenine nucleotide system

Abstract

An empirical dependence allowing one to identify rhythmic fluctuations of stable and unstable state in respect of hypoxia in the process of adaptation has been developed on the basis of long-term investigation of changes in brain content of adenine nucleotides upon "hypobaric training" of rabbits. The function approximating this dependence enables one to predict the effective number of "hypobaric training" sessions providing for the adaptive reaction. Key Words: hypoxia; AMP; ATP; energy metabolism; adaptationThe response to hypoxia of organs and tissues with intense energy metabolism (for instance, brain and muscles) has several aspects. Versatile biochemical mechanisms of this response possess characteristic differences and tissue specialization. Adenosine triphosphate is a direct energy substrate for the majority of cellular functions. Proceeding from this, it seems reasonable to suggest the balance of adenine nueleotides for the basic component in analysis of adaptive mechanisms and estimation of adaptation efficiency.The creatine kinase reaction is an extremely effective mechanism of emergency correction of ATP level upon substantial (up to 3-fold) decrease in the rate of oxygen consumption [12]; this mechanism provides for not more than 5% modulations of ATP level. Although this mechanism has limited reserves, it is associated with regulatory systems of energy metabolism (respiratory chain enzymes and reduced equivalents in the mitoehondria) operating at other levels to prevent energy deficit upon hypoxia. Since these systems are very complex, it is impossible to Department of Biochemistry, St. Petersburg University;, Department of Applied Mathematics, Nizhnii Novgorod State Technical University; Department of Biochemistry, Nizhnii Novgorod Medical Academy describe their function even with the use of a simplified kinetic model. Meanwhile, empirical dependences characterizing changes in the concentrations of adenine nucleotides, guanidine phosphates, and other energy metabolites can be employed for solution of some practical problems, for instance, for definition of criteria of the resistance to hypoxia. The set of dependencies can be varied in the search for optimal decision taking into consideration the informativeness of parameters, the difficulties of their experimental measurements, etc.The state of the adenine nucleotide system, specifically, the ATP and AMP concentrations, is a sensitive marker of brain resistance to hypoxia [I0,1 I, 13]. Is has been shown that brain ATP content decreases after "hypobaric trainings" which provide a 2-4-fold increase in the resistance to hypoxia.We studied the relationships between the coneentration of major energy metabolites (ATP, AMP, ADP, and creatine phosphate) in hypobaric hypoxia and isehemia and approximated them in an .attempt to predict the state of the brain energy metabolism.In the present work we measured brain concentrations of adenine nucleotides and obtained an empirical dependence describing changes in the AM P concentration relative to brain ATP cont...

Approaches to Prediction of the Adaptive State of the Brain Energetic System under Conditions of Hypoxia

“…The method of approximation of empirical dependence was previously tested by us for other parameters of energy metabolism in the brain: for analysis and prognosis of ¿ nal concentration of ATP from activity of mitochondrial enzyme complexes [14]; for evaluation of kinetic characteristics of oxidative phosphorylation in the brain of experimental animals [13]; for prediction of the limits of organism's resistance to hypoxia [8], etc. The use of the method of approximation of empirical dependencies in this study makes it possible to predict mCK activity by calculation methods and to determine ATP content in the brain under extreme conditions.…”