Mixed dead-end and product inhibition

Products usually bear some resemblance to the substrates. Consequently, we shall often find that products combine with some improper enzyme form to yield a dead-end complex (Plowman, 1972 Fromm, 1975). Formation of such complexes is a very frequent case, and it does not require nonphysiological substrates. It is common in Ae normal physiological direction of a reaction, since in vivo the 

In a Steady-State Ordered Bi Bi mechanism, A combines with the enzyme and induces the formation of the binding site for B. However, P, which bears a stmctural similarity to B, may bind instead of B. 

When a product, P, combines with an another enzyme form, in addition to one it normally combines with as a substrate in the reverse direction, certain terms in the denominator of the rate equation are multiplied by the factor ii+P/Ki), where is the dissociation constant of the product from the deadend complex. 

If the denominator terms that are multiplied already contain a P term, the resulting rate equation wfil obtain a P term, and the resulting inhibition will be parabolic. 

In this case, the denominator terms that are multiplied by (l+P/Xj) are those corresponding to the relative concentration of the EA complex. These terms are found in the numerator of the distribution equation for [EA]/[Eol for the Ordered Bi Bi mechanism (Chapter 9 Eq. (9.13)). In the presence of A, B, and P (and the absence of Q), the numerator term of the distribution equation for [EA]/[Eo] contains an [A] term and an [A][P] term. Consequently, the rate equation in the presence of P (from Eq. (9.19)) is  

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Substrate Inhibition and Mixed Dead-End and Product Inhibition... 

Although the basis of product inhibition is somewhat different from that of dead-end inhibition, the end results may nevertheless be categorised in the same way, depending upon whether the inhibitor affects the slopes, the intereepts or both in plots of e/v against 1/[S]. Thus the terms competitive, non-competitive, uncompetitive and mixed still apply. If we consider Eqn. 17, a slope effect will be seen, with A as the varied substrate, if the inhibitor affects the term, the both ... 

Figure 9 shows the graphical presentation of Eq. (1134), a plot of i/Uo versus 1/5, in the presence of increasing concentrations of P. The double reciprocal plot has an unusual appearance. Thus, the mixed product and dead-end inhibition by P can be distinguished from the normal product inhibition by P from the fact that the family of straight lines does not intersect at a common point. 

Figure 9. Mixed product and dead-end inhibition in an Ordered Bi Bi system. P reacts with EA as well as with EQ (Scheme (11.31)). The plot of i/un versus l/B is slope-parabolic, intercept-linear.

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