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Allosteric Enzymes Are Affected by Signal Molecules 187

Allosteric Enzymes Are Affected by Signal Molecules 187

Precursor ABC Product

Precursor ABC Product

FIGURE 7.38 Feedback Inhibition of Metabolic Pathways

Feedback occurs when the product of an enzyme-catalyzed pathway interacts with one of the enzymes in the pathway, usually the first, to inhibit (negative feedback) or promote (positive feedback) the activity of that enzyme. The activities of the other enzymes in the pathway (#2, #3 and #4) are usually unaffected.

Enzymes May Be Directly Regulated

The activity of an enzyme or other protein may be controlled at the genetic level by deciding whether or not to synthesize the protein. Such genetic regulation is discussed in later chapters. More rapid cellular responses are possible if the activity of an existing protein is controlled. Although most of the following examples apply to enzymes, it should be realized that all types of proteins, including regulatory proteins, transport proteins and mechanical proteins, can be similarly modified and their activity regulated.

The rate at which the majority of enzymes work depends simply on the level of substrate that is available and how much enzyme protein is present. The latter, of course, depends on the level of expression of the gene encoding the enzyme. However, a significant proportion of enzymes are also directly regulated in a variety of ways. This has the advantage that it is more or less instantaneous. Such regulation is usually reversible, so that an enzyme that is temporarily inactive is not destroyed, but can be used again later if needed.

Regulated enzymes are usually found at the beginnings, ends or branch points of metabolic pathways. Control is exerted at these critical points and the enzymes in between merely operate automatically. Many biosynthetic pathways are regulated by negative feedback (Fig. 7.38).The final product of the pathway inhibits the first enzyme in the pathway. This way, when sufficient product has accumulated, the cell does not waste materials making any more.

Many biosynthetic pathways are branched and lead to several final products. In this case, the enzymes at each branch point may be controlled by the products of the separate branches. An example is the synthesis of the aspartate family of amino acids. Aspartate is the precursor to four other amino acids (Lys, Met, Thr, and Ile), all of which inhibit, by feedback, both their own branch and the pathway as a whole (Fig. 7.39).

Allosteric Enzymes Are Affected by Signal Molecules

Enzymes that are regulated by binding small molecules, at a site away from the active site, alternate between two forms with different 3-D conformations and are known as allosteric enzymes. Interconversion between the active and inactive form involves a change in shape and usually also assembly or disassembly of the protein subunits that make up the enzyme. In the active form, the active site is available for substrate, whereas in the inactive form, the active site is often blocked or altered in shape so that allosteric protein Protein that changes shape when it binds a small molecule negative feedback Form of negative regulation where the final product of a pathway inhibits the first enzyme in the pathway

Enzymes located at critical points in metabolic pathways are often regulated by altering the activity of the protein.

End products of metabolic pathways often inhibit the enzyme that performs the first step of the pathway.

FIGURE 7.39 Feedback Inhibition of Aspartate Family Pathway

Aspartate can be converted into four other amino acids. Negative feedback, as shown by arrows, is exerted on the production of the four amino acids shown in yellow.

FIGURE 7.39 Feedback Inhibition of Aspartate Family Pathway

Aspartate can be converted into four other amino acids. Negative feedback, as shown by arrows, is exerted on the production of the four amino acids shown in yellow.

FIGURE 7.40 Allosteric Enzymes Change Shape

An enzyme that has both an active site and an allosteric site is altered in shape when a signal molecule binds. The altered shape also affects the configuration of the active site.

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