Metabolic pathways proceed in a stepwise, highly regulated manner that maximizes the use of available nutrients and energy. The cell responds to environmental conditions by adopting those metabolic reactions that most favor its growth and survival. Because enzymes are critical to these reactions, the regulation of metabolism is largely the regulation of enzymes by an elaborate system of checks and balances. Let us take a look at some general features of metabolic pathways.
Patterns of Metabolic Pathways
Metabolic reactions rarely consist of a single action or step. More often, they occur in a multistep series or pathway, with each step catalyzed by an enzyme. An individual reaction is shown in various ways, depending on the pathway pattern (figure 1). The product of one reaction is often the reactant (substrate) for the next, forming a linear chain of reactions. Many pathways have branches that provide alternative methods for nutrient processing. Others take a cyclic form, in which the starting molecule is regenerated to initiate another turn of the cycle. Pathways generally do not stand alone; they are interconnected and merge at many sites.
Fig1. Patterns of metabolic pathways. In general, metabolic pathways consist of a linked series of individual chemical reactions that produce intermediary metabolites and lead to a final product. These pathways occur in several patterns, including linear, cyclic, and branched. Anabolic pathways involved in biosynthesis result in a more complex molecule, each step adding on a functional group, whereas catabolic pathways involve the dismantling of molecules and can generate energy. Virtually every reaction in a series involves a specific enzyme.
Every pathway has one or more enzyme pacemakers that set the rate of a pathway’s progression. Regulation of pacemaker enzymes proceeds on two fundamental levels. Either the enzyme itself is directly inhibited or activated, or the amount of the enzyme in the system is altered (decreased or increased). When factors affect the enzyme directly, the system can be finely controlled or “tuned.” When regulation is at the genetic level (enzyme synthesis), control is slower and less sensitive.
Direct Controls on the Action of Enzymes
The bacterial cell has many ways of directly influencing the activity of its enzymes. It can inhibit enzyme activity by supplying a molecule that resembles the enzyme’s normal substrate. The “mimic” can then occupy the enzyme’s active site, preventing the actual substrate from binding there. Because the mimic cannot actually be acted on by the enzyme and a product is not released, the enzyme is effectively shut down. This is one example of competitive inhibition, because the mimic is competing with the substrate for the binding site (figure 2).
Fig2. Examples of two common modes of inhibition that regulate enzyme action.
Another form of competitive inhibition can occur with special types of enzymes that have two binding sites: the active site and another area called the regulatory or allosteric site (figure 2). The action of these enzymes is controlled by the binding of molecules other than the substrate in the regulatory site. Often the regulatory molecule is the product of the enzymatic reaction itself. This provides a negative feedback mechanism that can slow down enzymatic activity once a certain concentration of product is produced.
Noncompetitive inhibition is a third mechanism that does not involve an inhibitor molecule competing with substrate for the active site or disabling the active site. This type of inhibitor binds to the entire enzyme-substrate complex and prevents the enzyme from completing its action on the substrate.
Controls on Enzyme Synthesis
Controlling enzymes by controlling their synthesis is another effective mechanism. Because enzymes do not last indefinitely, they eventually degrade and must be re placed. This cycle works into the scheme of the cell, where replacement of enzymes can be regulated according to cell demand. The mechanisms of this system are genetic in nature; that is, they require regulation of DNA and protein synthesis.
Enzyme repression is a means to stop further synthesis of an enzyme some where along its pathway. As the level of the end product from a given enzymatic reaction has built to excess, the genetic apparatus responsible for replacing these enzymes is automatically suppressed (process figure 3). The response time is longer than for feedback inhibition, but its effects are more enduring.
Process Fig3. One type of genetic control of enzyme synthesis: enzyme repression. (1–5) Genetic controls are active and the enzyme is synthesized continuously until enough product has been made. (6)–(7) Excess product reacts with a site on DNA that regulates the enzyme’s synthesis, thereby inhibiting further enzyme production.
A response that resembles the inverse of enzyme repression is enzyme induction. In this process, enzymes appear (are induced) only when suitable substrates are present; that is, the synthesis of enzyme is induced by its substrate. This response enables the organism to adapt to a variety of nutrients, and it also prevents a microbe from wasting energy by making enzymes for which substrates are lacking.
