Metabolic reactions coupling

The pharmacokinetic implications of these findings are not straightforward. One important factor that must also be considered is hepatic extraction, which is higher for lovastatin than for its hydroxy acid metabolite [188], Some lactones are useful prodrugs of HMG-CoA reductase inhibitors due to this organ selectivity coupled with the efficiency of enzymatic hydrolysis. However, other factors may also influence the therapeutic response, in particular the extent and rate of metabolic reactions that compete with or follow hydrolysis, e.g., cytochrome P450 catalyzed oxidations, /3-oxidation, and tau-... 

According to the second law, the dissipation function must be positive if not zero, which of course is to be expected here, since we are dealing with a spontaneously occurring passive process. The thermodynamic force A/x+, which contains both a concentration-dependent component and an electrical component, is the sole cause of the flow J+. In a system in which more than one process occurs, each process gives rise to a term in the dissipation function consisting of the product of an appropriate force and its conjugate flow. In the case of active transport of the cation, as found, for example, in certain epithelial tissues, the cation flux is coupled to a metabolic reaction. If we represent the flow or velocity of the reaction per unit area of membrane by Jr, the appropriate force driving the reaction is... 

The coupling between chemical reactions and transport in biological membranes, such as the sodium and potassium pumps, is known as active transport, in which the metabolic reactions cause the transport of substances against the direction imposed by their thermodynamic force of mainly electrochemical potential gradients. 

Equation (10.157) implies that no coupling exists between sodium and chloride flows, while the sodium flow JNa is coupled to the metabolic reaction JT. Equations (10.156)—(10.158) can be applied to the following experimental cases ... 

Here, J refers to inward fluxes, while A/jlm = /li,ux - fxtm. Eqs. (10.187)-(10.189) indicate the coupling between certain flows and lack of coupling between others. The metabolic reaction occurring in the cell is not coupled to any of the flows. After a certain time has passed the system reaches a state in which the concentrations of M and N, but not that of O, become constant, so that in the stationary state we have... 

Table 3 Autotrophic reduction-oxidation reactions coupled to CO2 assimilation. The most common carbon assimilation pathways for each type of metabolism are listed, with alternative modes of CO2 fixation provided in parentheses. The free energy yield of the reaction is provided for pathways that do not require light.

In yeast and mycelial fungi, xylose is metabolized via coupled oxidation-reduction reactions . Xylose reductase is the enzyme involved in the reduction of xylose to xylitol. Sequential enzymatic events, through the oxidation of xylitol to xylulose, lead to the utilization of xylose. Many yeast species utilize xylose readily, but the ethanol production capability is very limited. Only a few yeast species effectively produce ethanol from xylose these include Pachysolen tan-nophilus, Candida shihatae and Pichia stipitis [80]. The production of ethanol from xylose by these three yeast strains has been studied extensively in recent years. Recently, genetically engineered yeast strains have been constructed for more effective conversion of xylose to ethanol. 

Consider, for example, the development and reproduction of bacterial cells. These are open systems in the thermodynamic sense the bacterial cell continuously acquires food from its environment and excretes waste products into its environment. If we were to consider the bacterial cells alone, without reference to the environment, we would find that the process was endergonic, largely as a result of the substantial decrease in entropy associated with the increase in order. Such an endergonic process would not be thermodynamically possible in itself. However, the metabolic reactions which are coupled with the development of cells are sufficiently exergonic to enable the development to occur, in full accord with the second law. 

Under standard conditions, A cannot be spontaneously converted into B and C, because AG is positive. However, the conversion of B into D under standard conditions is thermodynamically feasible. Because free-energy changes are additive, the conversion of A into C and D has a AG° of — 3 kcal mol ( 13 kj moU ), which means that it can occur spontaneously under standard conditions. Thus, a thermodynamically unfavorable reaction can be driven by a thermodynamically favorable reaction to which it is coupled. In this example, the chemical intermediate B, common to both reactions, couples the reactions. Thus, metabolic pathways are formed by the coupling of enzyme-catalyzed reactions such that the overall free energy of the pathway is negative. 

These might be used, for example, to define the coupling of salt flux or water flux to a metabolic reaction. Our aim, however, in the introduction of the osmotic coupling coefficient, was to define a parameter that would reflect the relation between metabolically coupled salt flux and volume flow. 

While we don t need copper to transport oxygen around our bodies, we do need some copper in our diets in order to utilize the oxygen. Every cell in the body needs oxygen to survive. When the oxygen is delivered by hemoglobin, it is put to use in a variety of metabolic reactions. These reactions are catalyzed by enzymes that require copper to function. The amount of copper we need to consume is quite small — only a couple of milligrams a day, which we find in foods such as oysters, crab, lobster, red meat, nuts, soybeans, and bran there s even some in our drinking water. 

Two substantial reviews and discussions of biological and cellular processes in terms of electrodics have been published by KelF and Berry. Berry emphasized that an exergonic oxidation reaction can initiate an electrochemical process without direct chemical coupling, and, thus, the biological cell is a complex electrochemical device, rather than a chemically powered heat engine, and metabolic reactions are electrochemical processes, giving rise to proton currents. 

Kedem ° attempted to circumvent the paradox implicit in the driving of vectorial transport processes with supposedly scalar chemical forces by introducing a vectorial cross coefficient in a non-equilibrium thermodynamic definition of active transport. Jardetzky , however, stated that the direct coupling between a metabolic reaction and a transport process, implied by Kedem s vectorial cross coefficient, was impossible because it would contravene the Curie principle (see also ref. 11). Katchalsky and Kedem, later supported by Moszynski et al, answered the criticism of Jardetzky by saying that Langeland had shown that the principle of Curie applies... 

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