Enzyme regulation velocity curves

Relationship between the initial velocity (v) and the substrate concentration [S] for an allosteric enzyme that shows a heterotropic effect with constant Vmax but with varying ATq.s- Curve a is obtained in the absence of any modulators, curve b in the presence of a positive modulator, and curve c in the presence of a negative modulator. Regulation is achieved by modulation of ATq.s without change in F ax. 

Figure 10.15 Quantitative description of the MWC model. In this description of the MWC Monod, Wyman, and Changeaux) model, fractional activity, K is the fraction of active sites bound to substrate and is directly proportional to reaction velocity a is the ratio of [S] to the dissociation constant of 5 with the enzyme in the R state and L Is the ratio of the concentration of enzyme in the T state to that in the R state, The binding of the regulators ATP and CTP to ATCase changes the value of L and thus the response to substrate concentration. To construct these curves, the formula on page 200 was used, with c = 0.1 and n — 6.

Fig. 20.13. Allosteric regulation of isocitrate dehydrogenase (ICDH). Isocitrate dehydrogenase has eight subunits, and two active sites. Isocitrate, NAD, and NADH bind in the active site ADP and Ca are activators and bind to separate allosteric sites. A. A graph of velocity versus isocitrate concentration shows positive cooperativity (sigmoid curve) in the absence of ADP. The allosteric activator ADP changes the curve into one closer to a rectangular h5 perbola, and decreases the (S0.5) for isocitrate. B. The allosteric activation by ADP is not an all-or-nothing response. The extent of activation by ADP depends on its concentration. C. Increases in the concentration of product, NADH, decrease the velocity of the enzyme through effects on the allosteric activation.

Enzymes displaying classical Michaelis-Menten kinetics, as discussed above, are limited in their ability to maintain substrate levels within small tolerances, since the hyperbolic substrate-velocity relationship dictates that the responsiveness to change in substrate concentration decreases as the actual substrate level increases (Figure 1, curve a). However, many regulable enzymes are more flexible than this in their response to substrate, demonstrating the phenomenon of cooperativity (Citri, 1973). These enzymes have more than one catalytic site, generally on different polypeptides, and these sites communicate their status to each other. 

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