A (biológiai) élet folyamatszabályozása

Regulatory Enzymes Act as Metabolic Valves

Figure 14-16

Although not at equilibrium with their surroundings, adult organisms generally exist in a steady state. A constant influx of fuel and nutrients and a constant release of energy and waste products allow the organism to maintain a constant composition. When the steady state is disturbed by some change in external circumstances or fuel supply, the temporarily altered fluxes through individual metabolic pathways trigger regulatory mechanisms intrinsic to each pathway. The net ef fect of all of these adjustments is to return the organism to the steady state to achieve homeostasis. Because of the central role of ATP in cellular activities, evolution has produced catabolic enzymes with regulatory properties that ensure a high steady-state concentration of ATP, "high" in this context meaning high relative to the breakdown products ADP and AMP.

The flux through a biochemical pathway depends on the activities of the enzymes that catalyze each reaction. For some of the enzymes in a pathway such as glycolysis, the reaction is essentially at equilibrium within the cell; the activity of such an enzyme is sufficiently high that the substrate is converted to product as fast as the substrate is supplied. The flux through this step is essentially substrate-limited – determined by the instantaneous concentration of the substrate.

Other cellular reactions are far from equilibrium. In the glycolytic pathway, the equilibrium constant (K'eq) for the reaction catalyzed by phosphofructokinase-1 is about 250, but the mass action ratio [fructose-1,6-bisphosphate][ADP]/[fructose-6-phosphate][ATP] in a typical cell in the steady state is about 0.04. (The intracellular concentrations of some glycolytic enzymes and reactants are given in Table 14-2.) The reaction is so far from equilibrium because the rate of conversion of fructose-6-phosphate to fructose-1,6-bisphosphate is limited by the activity of PFK-1. Increased production of fructose-6-phosphate by the preceding enzymes in the glycolytic pathway does not increase the flux through this step, but instead leads to the accumulation of the substrate, fructose-6-phosphate. Thus PFK-1 functions as a valve, regulating the flow of carbon through glycolysis; increasing the activity of this enzyme (by allosteric activation, for example) increases the overall flux through the pathway. Metabolite flux through this pathway is determined not by mass action (by substrate and product concentrations) but by how far this enzymatic valve is "opened."
In every metabolic pathway there is at least one reaction that, in the cell, is far from equilibrium because of the relatively low activity of the enzyme that catalyzes it (Fig. 14-16):

Regulation of the flux through multistep pathways occurs at steps that are enzymelimited. At each of these steps (orange arrows), which are generally exergonic, the substrate is not in equilibrium with the product because the enzyme-catalyzed reaction is relatively slow. The substrate for this reaction tends to accumulate, just as river water accumulates behind a dam. In the substrate-limited reactions (blue arrows) the substrate and product are essentially at their equilibrium concentrations. At the steady state, all of the reactions in the sequence occur at the same rate, which is determined by the rate-limiting step.
(Lehninger-Nelson-Cox: Pricniples of Biochemistry, 426.o.)


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