Nonequilibrium reaction

In vivo, under steady-state conditions, there is a net flux from left to right because there is a continuous supply of A and removal of D. In practice, there are invariably one or more nonequilibrium reactions in a metabolic pathway, where the reactants are present in concentrations that are far from equilibrium. In attempting to reach equilibrium, large losses of free energy occur as heat, making this type of reaction essentially irreversible, eg. 

Such a pathway has both flow and direction. The enzymes catalyzing nonequilibrium reactions are usually present in low concentrations and are subject to a variety of regulatory mechanisms. However, many of the reactions in metabolic pathways cannot be classified as equilibrium or nonequilibrium but fall somewhere between the two extremes. 

It may be identified as a nonequilibrium reaction in which the of the enzyme is considerably lower than the normal substrate concentration. The first reaction in glycolysis, catalyzed by hexokinase (Figure 17-2), is such a flux-generating step because its for glucose of 0.05 mmol/L is well below the normal blood glucose concentration of 5 mmol/L. 

Glycolysis Is Regulated at Three Steps Involving Nonequilibrium Reactions... 

Glycolysis is regulated by three enzymes catalyzing nonequilibrium reactions hexokinase, phosphoffuc-tokinase, and pyruvate kinase. 

Three nonequilibrium reactions catalyzed by hexoki-nase, phosphofructokinase, and pyruvate kinase prevent simple reversal of glycolysis for glucose synthesis (Chapter 17). They are circumvented as follows ... 

The pathway of gluconeogenesis in the liver and kidney utilizes those reactions in glycolysis which are reversible plus four additional reactions that circumvent the irreversible nonequilibrium reactions. 

An important point in the regulation of these processes is that all the reactions from mitochondrial NADH, to and including cytochrome c, are near-equilibrium (Figure 9.26(a)) (Appendix 9.8) that is, there is only one reaction in the electron transfer chain that is non-equihbrium - the terminal reaction catalysed by cytochrome oxidase. There is some similarity with the process of glycolysis in which the initial reaction and the terminal reactions are the nonequilibrium reactions (Figure 9.26(b)). 

Several kinetic models have appeared to describe phosphorus reactions in soils. Enfield (1978) classified models for estimating phosphorus concentrations in percolate waters derived from soil that had been treated with wastewater into three categories (1) empirical models that are not based on known theory (2) two-phase kinetic models that assume a solution phase and some adsorbed phase and (3) multiphase models, which include solution, adsorbed, or precipitated phases. Mansell and Selim (1981) classified models as shown in Table 9.2. The reader is urged to consult this reference for a complete discussion of the phosphorus kinetic models. For the purpose of this discussion, attention will be given to models that assume reversible phosphorus removal from solution, which can occur simultaneously by equilibrium and nonequilibrium reactions, and mechanistic multiphase models for reactions and transport of phosphorus applied to soils. 

Mathematical models that assume reversible phosphorus removal from solution to occur simultaneously by equilibrium and nonequilibrium reactions Transport models that assume two types of phosphorus sorption sites... 

Apply spreadsheet, Excel, to compute the equilibrium constant (/ eq) and the mass-action ratio (Q) for each reaction. Identify and rationalize the futile cycles (Koshland, 1984) as possible sites of regulation in the glucose metabolism, noting that a regulatiory enzyme will catalyze a nonequilibrium reaction under intracellular conditions. This can be accomplished by comparing the established equilibrium constant for the reaction with the mass-action ratio as it exists within the cells. 

HI. A. 2. Comparison of the energetics of nonequilibrium reactions with their equilibrium alternatives. 87... 

Suarez, R.K., J.F. Staples, J.R.B. Lighton, and T.G. West (1997). Relationships between enzymatic flux capacities and metabolic flux rates nonequilibrium reactions in glycolysis. Proc. Natl. Acad. Sci. USA 94 7065-7069. 

Nonequilibrium reactions can be detected by determining metabolite concentrations in the tissue of interest. Conventionally, a tissue sample is rapidly frozen by compression between metal plates that have been cooled to 77 K by immersion in liquid nitrogen (freeze-clamping). This procedure rapidly halts any enzymatic processes that might alter the metabolite concentrations the concentrations can then be determined by enzymatic or chemical assays. Recently, 31P-NMR spectroscopy has shown considerable value in measuring the concentrations of such metabolites as ATP, ADP, AMP, phosphate, and phosphocreatine in living cells or tissues. 

This simple example is relevant to many topics discussed in subsequent chapters, for example, the behavior of bicarbonate and carbon dioxide. Also, recognition of the difference between reversible (equilibrium) and irreversible (nonequilibrium) reactions is important to an imderstanding of the role of enzymes in catalyzing various reactions. 

In this physiologically irreversible (nonequilibrium) reaction, the high-energy group of phosphoenolpyruvate is... 

Gluconeogenesis from pyruvate is essentially the reverse of glycolysis, with the exception of three nonequilibrium reactions (Figure 15-1). These reactions are... 

Regulation of liver 6-phosphofructokina.se and fructose-1,6-bisphosphatase. These multimodulated enzymes catalyze nonequilibrium reactions, the former in glycolysis and the latter in gluconeogenesis. Note the dual action of fructose-2,6-bisphosphate (F-2.6-BP), which activates phosphofnictokinase (PFK-1) and inactivates fructose-1,6-bisphosphatase. The activity of F-2.6-BP is under hormonal and substrate regulation (Figure 15-6). = positive effectors 0 = negative effectors. 

EFFECT OF NONLINEAR ADSORPTION AND DISPERSION ON THE INTERPRETATION OF NONEQUILIBRIUM REACTIONS... 

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