What is Enzyme Regulation?

Enzyme regulation is very important. You want to control how fast an enzyme is working based on the ability of substrate so not to be wasteful.

On a fundamental level enzyme activity is controlled by regulating the amount of copies of a particular enzyme (transcriptional regulation).

Types of Enzyme Regulation

I. Irreversible Inhibition

Agents which bind covalently to enzymes and disrupt their function are irreversible inhibitors.

A few irreversible inhibitors bind noncovalently.

Irreversible inhibitors tend to be highly toxic

Penicillin is an irreversible inhibitor that binds to a bacterial enzyme that assists in the manufacturing of peptidoglycan cell walls

II. Competitive Inhibition

A molecule similar in structure to the substrate reversibly binds to the active site and inhibits the enzyme’s activity.

Competitive inhibitors raise the apparent Km but do not change the Vmax

III. Noncompetitive Inhibition (Allosteric Modulation)

Allosteric regulators are molecules that alter enzyme kinetics by noncovalently binding to the enzymes at locations far away from the active site, allosteric site.

The allosteric regulator thus alters the 3- D structure of the enzyme.

Allosteric effectors can activate or inhibit enzyme activity.

a. Homotropic activation

Substrate serves as an activator, and You achieved the typical S or sigmodical curve found in describing behavior of enzymes such as hemoglobin.

Oxygen binds to the most difficult site first.

This alters the conformation of the protein so the next subunit binds oxygen more easily.

This process is then repeated for the other two subunits.

This change in conformation caused by the progressive binding of a ligand is known as cooperativity and leads to sigmoid kinetics.

The binding of one ligand (substrate or modulator) changes the conformation of the protein.

This can increase or decrease the affinity for further ligands – Both positive and negative cooperativity exist

Fetal hemoglobin must have a higher affinity for O2 than adult hemoglobin because it steals the O2 from the adult

b. Heterotropic activation/inhibition

A different molecule other than the substrate serves as the allosteric activator/inhibitor.

Can either activate or repress enzyme activity.

Noncompetitive inhibitors do not resemble the substrate, so commonly act on more than one enzyme.

Unlike competitive inhibitors, they can’t be overcome by increasing substrate concentration the substrate.

IV. Feedback Inhibition

When the supply of final product is sufficiently high, the 1st reaction of the pathway is slowed down (negative feedback), this type of regulation is more prevalent than positive feedback.

You can also have it when the supply of final product is low the 1st reaction of the pathway is sped up (positive feedback).