Oxidative phosphorylation oscillator

These studies demonstrate the general mechanism of synchronization of biochemical systems, which I expect to be operative in even more complex systems, such as the mitochondrial respiration or the periodic activity of the slime mold Dictyostelium discoideum. As shown in a number of laboratories under suitable conditions mitochondrial respiration can break into self-sustained oscillations of ATP and ADP, NADH, cytochromes, and oxygen uptake as well as various ion transport and proton transport functions. It is important to note that mitochondrial respiration and oxidative phosphorylation under conditions of oscillations is open for the source, namely, oxygen, as well as with respect to a number of sink reactions producing water, carbon dioxide, and heat. 

A typical chemical system is the oxidative decarboxylation of malonic acid catalyzed by cerium ions and bromine, the so-called Zhabotinsky reaction this reaction in a given domain leads to the evolution of sustained oscillations and chemical waves. Furthermore, these states have been observed in a number of enzyme systems. The simplest case is the reaction catalyzed by the enzyme peroxidase. The reaction kinetics display either steady states, bistability, or oscillations. A more complex system is the ubiquitous process of glycolysis catalyzed by a sequence of coordinated enzyme reactions. In a given domain the process readily exhibits continuous oscillations of chemical concentrations and fluxes, which can be recorded by spectroscopic and electrometric techniques. The source of the periodicity is the enzyme phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate by ATP, resulting in the formation of fructose-1,6 biphosphate and ADP. The overall activity of the octameric enzyme is described by an allosteric model with fructose-6-phosphate, ATP, and AMP as controlling ligands. 

High intersex differences and ultradian (period of 6-12 h) oscillations in the activity of catalase were found in the Harderian gland of Syrian hamster, with peak activities in females exceeding those in males by several 100-fold [222]. In oxidative stress response, CAT is phosphorylated at Tyr 231 and Tyr 386 by tyrosine kinases c-Abl and Arg [223]. 

Among the many systems Racker used, one is a particulate system prepared by exposing beef mitochondria to sonic oscillation. The system can oxidize succinate and NADH but cannot couple the oxidation of the substrate to the phosphorylation of ADP. Coupling can be achieved by adding to the system two soluble proteins referred to by Racker as factor 1 (FJ and factor 4 (F4). F is a protein with ATPase activity obtained by sonic disintegration of mitochondria. F4 is prepared by alkaline extraction of the mitochondria. Fi, which has been extensively purified, is a decamer with a molecular weight of 284,000, each monomer weighing 26,000. 

When mitochondria are disrupted into small vesicles or fragments with detergents, or by sonic oscillation, some enzymes and enzyme systems remain associated with the particles, while some others are recovered in the soluble phase. The cytochromes and the flavoproteins of the respiratory chain are exclusively recovered in the membrane fractions and seem to be firmly bound to the membrane. The ability to couple oxidation to phosphorylation is usually lost upon fragmentatioiu however, if the submitochondrial particles are prepared very carefully, they can... 

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