ENZYMES Proteins  Elmhurst College
Lock and Key Theory Coenzyme - NAD+ Enzyme Regulation  Chemistry Department
Carboxypeptidase Enzyme Inhibitors  Virtual ChemBook

Enzyme Regulators

Feedback Inhibitors:

Metabolic reactions in the cell are controlled by regulating enzymes. Regulatory mechanisms involve not only inhibitory effects, but activating effects as well. Regulatory control is achieved by controlling a few key enzymes in a series of reactions which occur in sequential steps guided by complex arrays of enzymes. The product of one step becomes the substrate for the next step and so forth. The whole series can be regulated by controlling the first enzyme in the series. The first enzyme may be called the regulatory or allosteric enzyme.

The allosteric enzyme may be controlled by a feedback or end product inhibition at an allosteric site different from the active site. Allosteric means "other site" or "other structure". The interaction of an inhibitor at an allosteric site changes the structure of the enzyme so that the active site is also changed.

This means that the product of the last reaction inhibits the first enzyme in the series. If the final product accumulates to an excess, it inhibits the first enzyme and "switches off" the reaction. When the product molecule concentration is lowered, the inhibiting molecule is removed so that the first enzyme is "switched on" again.

See the graphic on the left. The substrate interacts with the enzyme-1 to form products. One of these products becomes the substrate for the next enzyme, and continues through several more enzymes. When a higher concentraion of final product begins to build up, it "feedsback" to the first enzyme and reacts at the allosteric site. The enzyme not changes shape so that the substrate does not fit iinto the active site, therefore no more reactions can take place.

The net result is that the final product or feedback inhibitor acts as the on-off switch for the first enezyme. When the concentration of product is high the enzyme is "turned off". But when the concentration of final product is low, the feedback inhibitor (final product) moves out of the allosteric site in a reversible reaction to "turn on" the enzyme once again.

Link to Chime Hexokinase - Boyer Tutorial

QUES. Explain in your own words how a feedback inhibitor works.

Activation of Zymogens:

In the digestion of food a variety of enzymes are active starting in the mouth with amylase. Several other enzymes are active in the stomach, but most digestion occurs in the small intestine.

Chyme is the final, partially digested and acidic, product of stomach digestion. The entry of chyme into the first part of the small intestine, the duodenum, stimulates a hormone called secretin to stimulate both the pancreas and the liver.

In response, the pancreas secretes the hormone insulin for use in the metabolism of glucose by the cells. In addition, a strongly alkaline pancreatic juice is secreted into the duodenum to neutralize the acidic chyme. In addition, pancreatic juice contains several enzymes including amylase (hydrolyzes starch) and steapsin (hydrolyzes lipids); and zymogens including trypsinogen, chymotrypsinogen, and procarboxypeptidase.

The entry of chyme into the duodenum also stimulates the secretion of intestinal juice. The intestinal juice includes a number of enzymes such as: lipase, sucrase, maltase, lactase, aminopeptidase, dipeptidase, and enterokinase. Enterokinase is used to activate the zymogen, trypsinogen, to trypsin.

trypsinogen + enterokinase ---> trypsin + octapeptide

The activation of trypsinogen to trypsin occurs as follows: Enterokinase hydrolyzes the peptide bond between amino acid residues 15 and 16 liberating a small peptide. The new amino terminal unit, 16, then interacts ionically with aspartic acid-194. This, in turn, alters the orientation of the lysine-145 and opens the active site on the enzyme.

Trypsin in turn is used to activate two other zymogens:

chymotrypsinogen + trypsin ---> chymotrypsin

procarboxypeptidase + trypsin ---> carboxypeptidase

The above three enzymes are all active in the hydrolysis of proteins.