Substrate cycles pathway

A totally different mechanism for improving sensitivity is known as the substrate cycle. It is possible for a reaction that is non-equilibrium in the forward direction of a pathway (i.e. A B, see below) to be opposed by a reaction... 

In some circumstances, substrate cycles may operate not only to regulate flux through biochemical pathways but to achieve the controlled conversion of chemical energy (i.e. ATP) into heat. This occurs in two conditions. 

E represents the enzymes catalysing the reactions in the pathway. Simultaneous activities of E2 and E5 produce a substrate cycle between A and B. In the no cycling condition, enzyme E5 is absent (or inactive). 

Figure 6.24 The gluconeogenic pathway indicating the glycolytic and gluconeogenic non-equilibrium reactions. The non-equilibrium reactions provide for the substrate cycles. (See Chapter 3 for a discussion of substrate cycles and their role in regulation.)...

Muscular work is accompanied by the production of ammonia, the immediate source of which is adenosine 5 -phosphate (AMP).301 302 This fact led to the recognition of another substrate cycle (Chapter 11) that functions by virtue of the presence of a biosynthetic pathway and of a degradative enzyme in the same cells (cycle A, Fig. 25-17). This purine nucleotide cycle operates in the brain303 304 as well as in muscle. The key enzyme 5-AMP aminohydrolase (AMP deaminase step a, Fig. 25-17) also occurs in erythrocytes and many other tissues.304 305 Persons having normal erythrocyte levels but an absence of this enzyme in muscles suffer from muscular weakness and cramping after exercise.306... 

Answer If the catabolic and biosynthetic pathways operate simultaneously, a certain amount of ATP is consumed in futile cycles (or substrate cycles ) in which no useful work is done. Examples of such cycles are that between glucose and glucose 6-phosphate and that between fructose 6-phosphate and fructose 1,6-bisphosphate. The net hydrolysis of ATP to ADP and Pj increases the consumption of oxygen, the terminal electron acceptor in oxidative phosphorylation. 

The substrate cycle has allowed a nearly 440-fold increase (87.9/0.2) in the flux through the pathway for only a 5-fold (12.5/2.5) change in the concentration of AMP. 

A substrate cycle is produced when a non-equilibrium reaction in the forward direction of a pathway is opposed by another non-equUibrium reaction in the reverse direction of the pathway. The two opposing reactions must be catalyzed by separate enzymes. 

Figure k. Examples of substrate cycles in the gluconeogenic/ glycolytic pathway. 

The reaction involves a substrate-level phosphorylation in which phosphate from 1,3BPG is transferred to ADP to form ATP. The enzyme functions in the glycolysis, gluconeogenesis, and Calvin cycle pathways. 

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