Lecture 17: Enzyme Regulation

Question 1

What are the four primary means for enzyme regulation?

Answer 1

Regulatory Protein (association) Compartmentation Allosteric Regulation Covalent Modification

Question 2

What is regulation by organization commonly seen in organelles within a larger cell?

Answer 2

Compartmentation

Question 3

What is the biologic goal for optimal regulation with [S] and Km?

Answer 3

[S] = Km

Question 4

Feedback Inhibition

Answer 4

First enzyme in multi-step pathway inhibited by final product in the pathways

Question 5

What type of enzymes often undergo allosteric regulation?

Answer 5

Oligomeric Enzymes

Question 6

What is the difference between negative and positive modulator?

Answer 6

Negative Inhibit, Positive Stimulate

Question 7

What is the difference between a homotropic and heterotropic regulators?

Answer 7

Homo = regulator is a substrate for its target enzyme (ex. O₂ for hemoglobin)

Hetero = regulator is a regulatory molecule that is not also enzyme’s substrate (can be activator or inhibitor) (ex 2,3-BPG)

Question 8

What type of binding curves to allosteric enzymes display?

Why?

Answer 8

Sigmoidal

Allows regulation by [S] more efficiently, can reach V_max in less-fold increase

Question 9

What type of regulation is ATCase?

Role?

What inhibits it?

What activates it?

Answer 9

Heterotropic Regulation (allosteric)

Pyrimidine Synthesis

Inhibit - CTP (pyrimidine)

Activate - ATP (purine nucleotide)

JC! Think about it, all you have to know is ATCase is a pyrimidine synthesis. SO–purines (reactants) up regulate, and pyrimidine (products) down regulate.

Question 10

What does covalent modification use to regulate enzymes?

Why is this optimal?

Answer 10

Post Translational Modification

You don’t have to resynthesize entire proteins, you can just quickly change structures

Question 11

What are the primary methods of PTM for regulatory mod?

Are these reversible?

Answer 11

Phosphorylation, Acetylation, Methylation

ADP-ribosylation

Usually

Question 12

What are the primary structural mods for covalent modification?

Are these reversible?

Answer 12

Prenylation (membranes), glycosylation, hydroxylation, fatty acid acylation

Sometimes

Question 13

What is the main irreversible covalent modification for regulation?

Answer 13

Proteolysis

Question 14

What are the two clases of phosphorylation?

What do these additions add or remove?

What residues do these target?

Answer 14

Kinase = + Phosphate Group

Phosphatase = - Phosphate Group

+ phosphate = add negative charge

• phosphate = remove negative charge

Hydroxyl R-groups–Serine, Threonine, Tyrosine

Question 15

What type of regulation to many signaling pathways in cancer use?

Example?

Answer 15

Phosphorylation

Small molecule inhibitors of tyrosine kinase inhibitors used in cancer treatment

Question 16

What is the target of reversible acetylation of proteins?

Answer 16

ε-Amino groups of Lysine residues

Question 17

What does lysine acetyltransferase catalyze?

Answer 17

Transfer of acetyl group of acetyl-CoA to the lysyl residue, forming N-acetyl lysine

Question 18

What is the purpose of Histone Deacetylase (HDACs) and Sirtuins (SIRT1-7)?

Answer 18

Deacetylation or ADP ribosylation of proteins

Question 19

What is the major process regulated by SIRT3?

What does this have a role in?

Answer 19

Mitochondrial NAD+ Dependent Deacetylase

Tumor suppression

Question 20

What type of regulation does glycogen phosprylase use?

Answer 20

Covalent (phosphorylation) and allosteric

Question 21

How are majority of metabolic pathways regulated?

Answer 21

Feedback inhibition through post-translational modification

PTMs son!

Question 22

What is regulation allows a rapid mobilization of an activy in response to physiologic demand?

Answer 22

Proteolysis

Question 23

The conversion of zymogens to active forms usually involves what?

Answer 23

Proteolysis