Enzyme Regulation

Question 1

Compartmentaltion

Answer 1

• ensures metabolic efficiency and simplifies regulation

Question 2

Regulatory Enzymes

Answer 2

• have special properties leading to regulatory roles in metabolism
• allosteric and covalently modulated enzymes

Question 3

Allosteric regulation

Answer 3

• enzymes are highly regulated by binding small molecules that can either decrease or increase activity
• Feedback inhibition: first enzyme in a multi-step pathway inhibited by the final product of the pathway
• modulator binds non-covalently to site other than active site
• negative modulator inhibit, positive stimulate

Question 4

Homotropic allosteric regulator

Answer 4

• a substrate for its target enzyme

Question 5

Heterotrophic allosteric regulator

Answer 5

• molecule that is not also the enzyme’s substrate

- can be activator or inhibitor

Question 6

ATCase

Answer 6

• CTP inhibits it, ATP activates it

- binding sites for allosteric modulators are on the regulatory units

Question 7

Covalent modifications

Answer 7

• regulate metabolic flow by post-translationally modifying key metabolic enzymes and proteins
• occurs by post translational modification of AA side chains
• regulatory modifications: phosphorylation acetylation, methylation, ADP-ribosylation
• Structural modifications: Prenylation, glycosylation, hydroxylation, and FA acylation
• Proteolysis - irreversible

Question 8

Phosphorylation

Answer 8

• reversible
• introduces 2 negative charges on proteins
• kinases add a phosphate to hydroxyl side chains
• phosphatase so remove a phosphate from a phosphorylated side chains

Question 9

Reversible Acetylation of Proteins at e-AMino Groups of Lys Residues

Answer 9

• acetylation neutralizes the positive charges on Lys residues
• sirtuins - involved in deacetylation
• SIRT1 - nucleus
• SIRT3 - mitochondria, is the major mitochondrial NAD+ dependent deacetylase involved in tumors suppression as well as many other physiological processes

Question 10

Post-translation modification regulation

Answer 10

• rapid
• doesn’t require new proteins to be made or degraded
• easily reversible

Question 11

Glycogen Phosphorylase

Answer 11

• activity of glycogen phosphorylase involves covalent modification, allosteric regulation, and a regulatory cascade sensitive to hormonal status that acts on the enzymes involved in phosphorylation an dephosphorylation

Question 12

Regulation of Metabolic pathways

Answer 12

• allosteric regulation by ADP/ATP and NAD+/NADH levels
• feedback inhibition
• PTM of metabolic enzymes

Question 13

Regulation of Enzyme activities by proteolysis

Answer 13

• irreversible
  -near ubiquitous
• rapid mobilization of an activity in response to physiologic demand
  -Met excision
  -signal peptide removal during translocation of a protein
  -N and C terminal processing proteins into their active forms
  Ex blood coagulation cascade and zymogens