The efficiency of enzymes in accelerating chemical reactions is crucial to the maintenance of life. Cells, in effect, must race against the unavoidable processes of decay, which—if left unattended—cause macromolecules to run downhill toward greater and greater disorder. If the rates of desirable reactions were not greater than the rates of competing side reactions, a cell would soon die. We can get some idea of the rate at which cell metabolism proceeds by measuring the rate of ATP utilization. A typical mammalian cell “turns over” (i.e., hydrolyzes and restores by phosphorylation) its entire ATP pool once every 1 or 2 minutes. For each cell, this turnover represents the utilization of roughly 107 molecules of ATP per second (or, for the human body, about 1 gram of ATP every minute).
The rates of reactions in cells are rapid because enzyme catalysis is so effective. Some enzymes have become so efficient that there is no possibility of further useful improvement. The factor that limits the reaction rate is no longer the enzyme’s intrinsic speed of action; rather, it is the frequency with which the enzyme collides with its substrate. Such a reaction is said to be diffusion-limited (see Panel 3–2, pp. 142–143).
The amount of product produced by an enzyme will depend on the concentration of both the enzyme and its substrate. If a sequence of reactions is to occur extremely rapidly, each metabolic intermediate and enzyme involved must be present in high concentration. However, given the enormous number of different reactions performed by a cell, there are limits to the concentrations that can be achieved. In fact, most metabolites are present in micromolar (10–6 M) concentrations, and most enzyme concentrations are much lower. How is it possible, therefore, to maintain very fast metabolic rates?
The answer lies in the spatial organization of cell components. The cell can increase reaction rates without raising substrate concentrations by bringing the various enzymes involved in a reaction sequence together to form a large protein assembly known as a multienzyme complex (Figure 3–54). Because this assembly is organized in a way that allows the product of enzyme A to be passed directly to enzyme B, and so on, diffusion rates need not be limiting, even when the concentrations of the substrates in the cell as a whole are very low. It is perhaps not surprising, therefore, that such enzyme complexes are very common, and they are involved in nearly all aspects of metabolism—including the central genetic processes of DNA, RNA, and protein synthesis. In fact, few enzymes in eukaryotic cells diffuse freely in solution; instead, most seem to have evolved binding sites that concentrate them with other proteins of related function in particular regions of the cell, thereby increasing the rate and efficiency of the reactions that they catalyze (see p. 331).
Eukaryotic cells have yet another way of increasing the rate of metabolic reactions: using their intracellular membrane systems. These membranes can segregate particular substrates and the enzymes that act on them into the same membrane-enclosed compartment, such as the endoplasmic reticulum or the cell nucleus. If, for example, a compartment occupies a total of 10% of the volume of
TE2 2 2 1 1 4 4 5 21 4 5 3 3 3 enzyme domains (C) (E) (D) etc.5 nm C acyl carrier domain termination domain (TE) PYRUVATE DEHYDROGENASE COMPLEX FATTY ACID SYNTHASE 3 1 20 nm