Lecture 13 - Enzyme Regulation

What are the two types of inhibitors and what type of molecules are they often?

Irreversible inhibitors react with an enzyme to permanently shut off the enzyme; they are often toxins or drugs. Reversible inhibitors bind to and can dissociate from the enzyme; they are often analogs of the substrate

Where does a reversible inhibitor usually bind?

To the free enzyme to prevent substrate binding, or to the ES complex to prevent the reaction

What is competitive inhibition and what are its effects on Vmax/Km and why?

A reversible non-covalent type of inhibition in which the inhibitor is structurally similar to the substrate and binds to the active site. Because it competes with substrate BINDING, it increases the Km (affinity for SUBSTRATE), but does nothing to Vmax (RATE of reaction)

What is the chance of substrate binding to enzyme when a competitive inhibitor is present at 1:1 ratio?

50% chance

What is the probability of substrate binding to active site when you have 5 times higher concentrations of substrate molecule?

5x higher binding probability

What is the probability of substrate binding to active site when you have 4 times higher concentrations of a inhibitor molecule?

1/5 probability

What is noncompetitive inhibition and what are its effects on Km/Vmax

Inhibitor does not interfere with the substrate binding to the active site. Substrate binds but enzyme cannot do anything/ The Vmax DECREASES because product formation is prevented. Km is unchanged because product can still bind

What is uncompetitive inhibition and what are its effects of Km/Vmax?

Inhibitors bind reversibly to ES complex at a site other than the active site (forming EIS complex). The Vmax and Km decreases because increased substrate concentration cannot overcome uncompetitive inhibition

What necessitates enzyme regulation?

Needed for maintenance of ordered state, conservation of energy, and responsiveness to environmental changes.

What is allosteric regulation and what are its two types?

Allosteric regulation entails the binding of effectors to an allosteric site in order to have a positive or negative effect on enzyme activity. The two models are concerted and sequential. In concerted, all subunits are changed at once from T to R or vice versa.

What type of curve does allosteric regulation have? How do activators or inhibitors affect the curve?

Sigmoidal curve like Hb. Activators move the curve to the left (small Km, high affinity). Inhibitors move the curve to the right (big Km low affinity)

What are some activators and inhibitors of the commitment step of glycolysis?

F2,6BP and AMP/ADP are activators; ATP and citrate are inhibitors

What are the factors that impact enzyme activity?

Substrate concentration, zymogen cleavage, covalent modification, changes in enzyme concentration. hormones, substrate concentration, temperature, and concentration of effectors

What types of enzymes catalyze phosphorylation and what amino acids are typically phosphorylated?

Protein kinases; Ser Thr Tyr (-OH)

What glycogen enzyme is inactive in the phosphorylated state, and what does it do?

Glycogen synthase; synthesizes glycogen

What glycogen enzyme is active in the phosphorylated state, and what does it do?

Glycogen phosphorylase; breaks down glycogen

What is covalent modification and what are some types of it?

Modifications in enzyme structure by covalent groups. Some include phosphorylation, methylation, acetylation, and nucleotidylation

What is metabolic control?

Influence of enzymes in a pathway in response to external signals in order to alter metabolite flow

What is metabolic regulation?

The steady-state flow of metabolites through a pathway is maintained

What is allosteric control?

AKA feedback inhibition, the excess of product from one reaction in a pathway inhibits of previous step from making product

What is genetic control?

Controlling gene expression for metabolome