Oscillators membrane/enzyme

As illustrated by the examples above, the key to understanding the PI pathway is to comprehend the nature of the regulation of discrete subcellular microdomains of the lipids. Any changes in a specific plasma membrane signaling pool, whether a transient oscillation in PtdIns(4,5)P2 or a more sustained change in rate of flux through the pathway in response to a stimulus, will result in changes in cytoskeletal structure, membrane enzyme activity, and pump or channel activity within the microdomains where the lipid resides. 

In these equations, Pj and P2 are the two conformational states of the transport protein, and equilibrium constants (K) and rate constants (k) in an electric field are shown to be these constants in zero field multiplied by a nonlinear term that is the product of A Me and the electric field across the membrane, Em. The r in these equations is the apportionation constant and has a value between 0 and 1 (14). This property of a membrane protein has been explored, and a model called electroconformational coupling has been proposed to interpret data on the electric activation of membrane enzymes (13-17). A four-state membrane-facilitated transport model has been analyzed and shown to absorb energy from oscillating electric fields to actively pump a substrate up its concentration gradient (see the section entitled Theory of Electroconformational Coupling). 

The earhest example of a membrane-enzyme oscillator was presented by Na-parstek, Caplan, and coworkers [52]. This oscillator consists of papain immobilized in a porous collodion membrane that is permeable to water, substrate, and ions. The membrane is cast as a thin film against a pH electrode and is exposed to an alkaline (pH 10) external solution of benzyl arginine ethyl ester (BAEE), which is a substrate... 

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... 

Some of the main types of cellular regulation associated with rhythmic behavior are listed in Table III. Regulation of ion channels gives rise to the periodic variation of the membrane potential in nerve and cardiac cells [27, 28 for a recent review of neural rhythms see, for example, Ref. 29]. Regulation of enzyme activity is associated with metabolic oscillations, such as those that occur in glycolysis in yeast and muscle cells. Calcium oscillations originate... 

As indicated above, theoretical models for biological rhythms were first used in ecology to study the oscillations resulting from interactions between populations of predators and preys [6]. Neural rhythms represent another field where such models were used at an early stage The formalism developed by Hodgkin and Huxley [7] stiU forms the core of most models for oscillations of the membrane potential in nerve and cardiac cells [33-35]. Models were subsequently proposed for oscillations that arise at the cellular level from regulation of enzyme, receptor, or gene activity (see Ref. 31 for a detailed fist of references). 

When the same kind of electrode is introduced in a solution with a high pH (i.e., pH= 10) and a lower substrate concentration (first order kinetics), an oscillation in time of the measured pH inside the membrane spontaneously occurs. This enzyme, which has been extensively studied, does not give oscillation for any conditions of pH and substrate concentration. The period of oscillation is around one-half minute, and the oscillation is abolished by introducing an enzyme inhibitor. The phenomenon can be explained by the autocatalytic effect and by a feedback action of OH- diffusion in from the outside solution. The diffusion of this ion is quicker than the diffusion of the substrate. There is a qualitative agreement between the computer simulation and the experimental results. 

The absence of oscillation in the bulk solution was checked by using both a second pH electrode and a dye. The oscillation inside the membrane is not an interaction between polyelectrolyte and glass surface the effect is destroyed in the presence of an inhibitor of the enzyme activity. 

Where within the mitochondria are specific enzymes localized One approach to this question is to see how easily the enzymes can be dissociated from mitochondria. Some enzymes come out readily under hypotonic conditions. Some are released only upon sonic oscillation, suggesting that they are inside the matrix space. Others, including the cytochromes and the flavoproteins that act upon succinate and NADH, are so firmly embedded in the inner mitochondrial membranes that they can be dissociated only through the use of non-denaturing detergents. 

As a model to explain oscillations in an enzyme reaction Chay (1981) proposed a model based on a feedback mechanism of proton gradients across a membrane. The activity of the key enzyme in the reaction depends on the pH of the inner compartment. Oscillations predicted in pH as well as enzyme activity and substrate concentrations were observed. Chay and Cho (1982) extended the concept and computationally obtained similar results of oscillating elements of the enzyme reactions. 

The effects of oscillating electric fields on ion accumulation processes are also explained by SCM calculations (20). The oscillations lead to periodic changes in the ionic concentrations that are functions of the frequency, but the percentage change is greatest in those concentrations with the lowest steady-state values. In particular, sodium on the inner surface and potassium on the outer surface show maximal changes at about 100-200 Hz. These two ionic concentrations normally control the activity of the Na, K-ATPase of cell membranes, and increases could stimulate the enzyme. 

Naparstek, A., D. Thomas S.R. Caplan. 1973. An experimental enzyme-membrane oscillator. Biochim. Biophys. Acta 323 643-6. 

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