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5 Control of enzyme activity Living organisms govern the rate of their metabolism by regu- lating both the amount and the activity of the enzymes catalyz- ing their metabolic reactions. Some of the control mechanisms involved are very complex and not yet completely understood, although much progress has been made. Proenzyme activation Some enzymes are produced in an inactive form, called a zy- mogen or proenzyme, and converted into an active form only when needed. For example, thrombin is an enzyme that causes blood to clot by catalyzing the conversion of the soluble pro- tein fibrinogen to the insoluble fibrin. Blood does not normally contain thrombin, but it does contain its inactive precursor, prothrombin. Only when prothrombin is converted to throm- bin (by another enzyme) does clotting result. The mechanism is shown in reaction (7). Feedback inhibition and enzyme repression Enzyme repression is the process by which the rate of synthesis of an enzyme is reduced in the presence of a metabolite, often the end product of a chain of reactions in which the enzyme in question operates near the beginning. In the natural state, an organism has control and regulatory mechanisms to avoid making too much of a compound, so cell resources can be bal- anced and preserved for the best distribution for cell growth. Regulatory mechanisms that are common include feedback inhibition at the enzyme level and regulation of gene expres- sion of the pathway enzymes by a repression-type mechanism. In the feedback-inhibition mechanism, a key enzyme, usually early in the metabolic pathway, is sensitive to the product com- pound of the pathway such that the enzyme has reduced activ- ity when the level of the product compound of the pathway is high in the cell. Feedback inhibition, also called allosteric control or enzyme repression, controls some metabolic pathways. One metabolite product of the pathway will reversibly inhibit the activity of an enzyme essential to an earlier reaction in the synthesis. A hypo- thetical sequence is shown in reaction (8). In this reaction, the end product D may suppress the activity of enzyme E2. When D reaches a certain concentration, it decreas- es the rate of its own synthesis by preventing the conversion of A to B; the intermediates, B and C, do not accumulate; and the starting material, A, is spared for other reactions for which it may be needed. As soon as the concentration of D decreases, the inhibition of enzyme E1 is relieved and the synthesis of D resumes. This phenomenon can be of great advantage to a cell because it allows the concentration of the product D to be accurately regulated. Positive allosteric control, or allosteric activation, has also been observed. In this case, the binding me- tabolite, which may be the product of another pathway, causes activation of the enzyme. Some enzymes are susceptible to allosteric control, both positive and negative, by a number of different metabolites. Enzyme induction Controls also exist at the level of enzyme synthesis. One of these controls is enzyme induction. For example, if the induc- ible enzymes E1, E2, and E3 are required to utilize substance A, the enzymes are not produced by the cell when A is not avail- able. Only in the presence of an inducer, which may be A or a related compound, are enzymes E1, E2, and E3 synthesized. Enzyme (continued) (7) (8) + ward ' s science