Regulation of Enzymes

Question 1

3 general reasons for enzyme regulation

Answer 1

1. maintenance of an ordered state in a timely fashion and without wasting resources
2. conservation of energy
3. rapid adjustment in response to environmental changes

Question 2

why is it important to regulate enzymes to rapidly adjust in response to changes?

Answer 2

many biological processes take place at a specific time, location and speed, so regulation of enzymatic activity or quantity is necessary

Question 3

4 methods of alteration of catalytic efficiency of enzyme activity

Answer 3

1. zymogen activation (cleavage of proenzyme)
2. allosteric regulation
3. covalent modification (phosphorylation)
4. association/dissociation and protein-protein interaction

Question 4

how is enzyme activity also regulated specifically in metabolic pathways?

Answer 4

1. feedback regulation

2. compartmentalization

Question 5

2 methods of regulating enzyme quantity

Answer 5

1. regulation of gene expression

2. enzyme turnover/degradation

Question 6

how are zymogens activated?

Answer 6

irreversible hydrolysis of one or more peptide bonds of the proenzyme/zymogen (the inactive precursor of enzyme), this causes a conformational change that forms the active site or exposes the active site

Question 7

what is the benefit of requiring proteolytic cleavage of proenzymes?

Answer 7

it allows the enzymes to NOT be destroyed, and therefore recruited quickly and instantly as they are needed, also the digestive, clotting and remodeling enzymes undergo reactions that would be disastrous to the body if they happened at inappropriate and unregulated times

Question 8

example of a hormone that is regulated by proteolytic cleavage?

Answer 8

preproinsulin synthesized by beta cells, then N terminal signal peptide is cleaved in the ER to make proinsulin, proinsulin is cleaved by prohormone convertase to insulin + c peptide within Beta cells in the pancreas

Question 9

example of a digestive protein that is regulated by cleavage?

Answer 9

trypsinogen

Question 10

example of functional plasma proteins that are regulated via cleavage?

Answer 10

prothrombin to thrombin, fibrinogen to fibrin

Question 11

example of connective tissue that is regulated by cleavage?

Answer 11

collagen is synthesized as procollagen

Question 12

what are allosteric enzymes?

Answer 12

activity that can be adjusted by reversible, non-covalent binding of a specific modulator to the regulatory sites (that are specific sites on surface of enzymes for activators and inhibitors) during allosteric regulation (cooperative) , indicates that there are usually multiple subunits (catalytic and regulatory)

Question 13

what does allosteric regulation kinetics look like?

Answer 13

a sigmoidal curve, reflecting the cooperative interactions between multiple protein subunits

Question 14

what occurs during positive allosteric regulation?

Answer 14

indirectly affects easier substrate binding to active site, so decreases Km and increases affinity

Question 15

what occurs during negative allosteric regulation

Answer 15

indirectly affects difficult substrate binding to active site, increases Km and decreases affinity

Question 16

what is an example of allosteric regulation?

Answer 16

PFK-1 is an allosteric enzyme, to which ATP is allosteric inhibitor and makes the Km increase, and AMP is an allosteric activator and makes Km decrease

Question 17

what is an example of allosteric regulation in hemoglobin?

Answer 17

2,3-BG is a negative allosteric effector, increasing Km and decreasing affinity for O2 binding to hemoglobin, meaning O2 release is easier in presence of 2,3-BG

Question 18

what occurs during covalent modification?

Answer 18

chemical groups added to enzymes are modified in reversible and covalent manner, changing enzymatic activity

Question 19

what is the most common covalent modification?

Answer 19

phosphorylation in response to stimulus (hormone or GF)

Question 20

what do protein kinases do?

Answer 20

add phosphate

Question 21

what do protein phosphatases do?

Answer 21

remove phosphate

Question 22

how is phosphorylation usually done?

Answer 22

the phosphate group is usually transferred from an activated donor like ATP to an amino acid (serine/threonine or tyrosine) on the regulatory enzyme, activating or inactivating enzymes or changing activity by changing Km or kcat, usually causes amplification cascade, allowing a quick response with less energy expenditure

Question 23

what is the benefit of phosphorylation of regulation of enzyme activity?

Answer 23

• is rapidly reversible, can quickly switch between active and inactive states
• timing can be adjusted
• inexpensive bc doesn’t require synthesis of new protein molecules
• can be rapidly amplified via kinase cascade

Question 24

what is an example of an enzyme controlled by both allosteric AND covalent modification

Answer 24

glycogen phosphorylase is activated by phosphorylation by phosphorylase kinase, and also positively allosterically activated by AMP

Question 25

what is an example of enzyme regulation by association?

Answer 25

a polymerized form of a molecule is active, unpolymerized is not. in fatty acid biosynthesis, the first committed step is acetyl-coa binding to citrate to make malonyl-coa, and then is inactivated by fatty acyl-coa to make malonyl-coa into acetyl coa (unpolymerized)

Question 26

what is an example of enzyme regulation by dissociation?

Answer 26

protein kinase A is in an inactive form when the regulatory subunits are bound to the catalytic subunits, but is activated when the regulatory subunits bind to cAMP (an allosteric activator) and separate them from the catalytic subunits, pka is active through the catalytic subunit monomers

Question 27

example of enzyme regulation by protein-protein interactions

Answer 27

calmodulin and Calcium bind together, and bind to the CaM kinase, activating it to phosphorylate metabolic enzymes like glycogen phosphorylase kinase, ion channels, transcription factors, synthesis and release of NT

Question 28

what is feedback regulation?

Answer 28

an enzyme that is early in a metabolic pathway, usually the committed step of the pathway, is inhibited by an end product

Question 29

example of feedback regulation

Answer 29

1. HMG-CoA reductase activity is regulated by intracellular cholesterol
2. 7alpha-hydroxylase activity is regulated by bile acids

Question 30

what is compartmentalization in enzyme regulation?

Answer 30

specific enzymes are kept only in their respective organelles

Question 31

how is enzyme quantity regulated?

Answer 31

synthesis and degradation by increasing rate of synthesis and decreasing rate of degradation, or both

Question 32

what are the protein degradation pathways?

Answer 32

1. lysosomal pathway

2. ubiquitin-proteasome pathway

Question 33

what is the lysosomal pathway?

Answer 33

degradation is under acidic conditions in lysosomes with NO ATP required, digests invading or long lifetime proteins, is not discriminatory for digestion (digests whatever)

Question 34

how is degradation speed influenced?

Answer 34

presence of ligands like substrates, coenzymes, metal ions, nutrients, hormones

Question 35

what is the ubiquitin-proteasome pathway?

Answer 35

digests the proteins of a short lifetime, labeling by ubiquitin followed by hydrolysis, ATP is needed