Allosteric factors

Other reactions are far from equilibrium. Allosteric factors that alter the activity of these enzymes can change the overall flux through the pathway. 

F6P is a phosphorylated form of fructose commonly found in cells. F6P is an intermediate in glycolysis, gluconeogenesis, the pentose phosphate pathway, and the Calvin cycle. F6P is a substrate in biosynthesis of the important allosteric factor regulating glycolysis, fructose-2,6-bisphosphate and is also an important precursor of amino sugars (last enzyme below). 

In the mitochondrial matrix, acety-CoA molecules are condensed to produce 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). The next step, catalyzed by HMG-CoA reductase, is the major flux-controlling step. HMG-CoA reductase is modulated by both reversible phosphorylation and allosteric factors, and the activity of the enzyme even shows a circadian rhythm. The regulating influences are summarized in Fig. 12-11, but the most germane factor is the level of cholesterol itself, which acts as a negative feedback inhibitor. Therefore, cells respond to a lack of cholesterol both by expressing more LDL receptors and by increasing their own synthesis of cholesterol. 

Silva, L.P., Yu, R.H., Calmettes, C., etal. (2012) Steric and allosteric factors prevent simultaneous binding of transferrin-binding proteins A and B to transferrin. Biochem J, 444 (2), 189-197. 

It is worth examining the possible magnitudes of the error with various scenarios. The maximal value for [A]/Ka can be approximated, assuming a system where response is directly proportional to receptor occupancy. Under these circumstances, Response = 0.3 = [A]/Ka/([A]/Ka + 1), which in this case is [A]/Ka = 0.5. Therefore, the pA2 is pKB + Log (2) (i.e., the pA2 will overestimate the affinity of the antagonist by a maximal factor of 2). If the insurmountable antagonist is allosteric antagonist that reduces the affinity of the receptor for agonist (a < 1), then the error will be <2. However, if the modulator... 

Na+,H+ antiporters (NHE) occur in synaptosomes, glia and neuroblastoma cells [60] (Fig. 5-8B). They are relatively inactive at neutral pH but with a decrease in intracellular pH they produce an efflux of protons at the expense of the Na+ gradient. The NHE transport stoichiometry is 1 1. Activation by an internal pH decrement apparently results from protonation of a cytoplasmic site, which allosterically increases the affinity of the proton ionophoric site. In some cells, the NHE is under additional control by receptor mechanisms. Several growth factors and hormones produce transient cytoplasmic alkalinization, probably by mediating a protein kinase... 

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