Enzyme Regulation

Question 1

Multiple steps in metabolic pathways allow

Answer 1

Efficient energy utilization

Question 2

What do interconnections in metabolic pathways ensure?

Answer 2

Efficient utilization of metabolites

Question 3

What are reversible reactions controlled by?

Answer 3

Changes in substrate

Question 4

Irreversible reactions are…

Answer 4

Enzyme regulated

Question 5

What is flux?

Answer 5

The rate at which the starting material is converted to the products of the pathway

Question 6

What are 3 ways flux is controlled through a pathway?

Answer 6

1. Enzymes in the pathway
2. Supply of starting material
3. Rate of product utilization

Question 7

Flux through a pathway is never faster than what?

Answer 7

The rate limiting step

Question 8

What is feedback regulation?

Answer 8

When the product of a pathway controls its synthesis

Question 9

2 types of feedback regulation

Answer 9

1. Product inhibition
2. Feedback inhibition

Question 10

List 5 factors involved in regulation of enzyme activity

Answer 10

1. Substrate conc
2. Product inhibition vs Feedback inhibition
3. Allosteric activation and inhibition
4. Cooperativity
5. Post-translational modification
   Phosphorylation/dephosphorylation
   Proteolysis to activate an inactive precursor called
   a zymogen

Question 11

For many enzymes, where is [S]?

Answer 11

Near Km

Question 12

When [S]&raquo_space;Km, the rxn velocity…

Answer 12

Doesn’t change with [S]

Question 13

When [S] &laquo_space;Km, the rxn velocity…

Answer 13

Changes in proportion to [S]

Question 14

According to the Michaelis-Menter Equation, how much change in substrate conc is necessary to access the full dynamic range of enzyme initial velocity?

Answer 14

~100 fold

Question 15

What is product inhibition?

Answer 15

When the product of an enzyme inhibits that enzyme

Question 16

What is feedback inhibition?

Answer 16

When the product of a metabolic pathway influences its production

Question 17

What two isozymes are controlled by different mechanisms?

Answer 17

Hexokinase and glucokinase

Question 18

Does hexokinase have high/low Km?

Answer 18

Low Km

Question 19

What is hexokinase inhibited by?

Answer 19

Its product glucose-6-P

Question 20

Does glucokinase have high/low Km?

Answer 20

High Km

Question 21

What is glucokinase regulated by?

Answer 21

Conc of glucose, making it a “glucose sensor”

Question 22

Whaat is allostery?

Answer 22

Process by which biological macromolecules transmit effect of binding at one site to an often distal, functional site, allowing for regulation of activity

Question 23

What 2 things does allostery require?

Answer 23

1. Binding
2. Change in conformation associated with binding

Question 24

What can allostery result in?

Answer 24

Activation or inhibition/positive or negative feedback

Question 25

Allosteric enzymes have ___ and ___ affinity conformations

Answer 25

low and high

Question 26

What does cooperativity apply to?

Answer 26

Multimeric enzymes En with n equivalent active sites

Question 27

What are homotropic allosteric modifiers?

Answer 27

substrates for the active site

Question 28

What are heterotropic allosteric modifiers?

Answer 28

Do not bind at active site; not substrates

Question 29

Heterotropic allosteric modifiers differ from...

Answer 29

Ligand at active site

Question 30

Heterotropic inhibitors stabilize a ___ affinity form of the active site

Answer 30

low

Question 31

Heterotropic activators stabilize a ____ affinity form of the active site

Answer 31

high

Question 32

What does PFK-1 do?

Answer 32

Incorporates phosphate from ATP into F6P to form F16BP

Question 33

What shape is the graph of PFK-1 velocity vs F6P substrate?

Answer 33

Sigmoidal - signature of + cooperativity

Question 34

PFK-1 has ___ identical subunits, each with 1 active site

Answer 34

4

Question 35

In the absence of substrate F6P, PFK-1 exists in the ___-state

Answer 35

T

Question 36

When F6P binds at 1 active site, all other sites...

Answer 36

Switch to high affinity R-state

Question 37

F6P is a...

Answer 37

homotropic allosteric activator

Question 38

ATP is what 2 things?

Answer 38

1. Substrate 2. Heterotropic inhibitor

Question 39

PFK-1 has what 2 different ATP binding sites on each subunit?

Answer 39

1. 1 ATP site is active site (where ATP is substrate) 2. Other ATP site is not active site, it stabilizes low affinity T-state for F6P

Question 40

F26BP is a....

Answer 40

Heterotropic activator

Question 41

F26BP activates...

Answer 41

PFK-1

Question 42

Where does F26BP not bind?

Answer 42

Active site of PFK-1/ Heterotropic allosteric activator

Question 43

What enzymes do phosphorylation/dephos. and on what residues?

Answer 43

Kinases do phosphorylation/dephosphorylation of serine, threonine, or tyrosine residues

Question 44

What enzymes do proteolysis that activate a precursor (zymogen/proenzyme)?

Answer 44

Proteases

Question 45

Protein kinases transfer... to hydroxyl groups of...

Answer 45

Protein kinases transger phosphate from ATP (NTP) to hydroxyl groups of ser, thr, tyr

Question 46

What do protein phosphatases do?

Answer 46

Remove phosphate from the enzyme

Question 47

AMP is a .... of ....

Answer 47

AMP is a heterotropic allosteric activator of glycogen phosphorylase

Question 48

High AMP in ___ cell

Answer 48

High AMP in a low energy cell

Question 49

What further stabilizes glycogen phosphorylase active form?

Answer 49

Phosphorylation

Question 50

Which of many enzymes are translated as inactive zymogens and activated by proteolysis?

Answer 50

Pancreatic digestive enzymes

Question 51

What is the blood clotting cascade controlled by?

Answer 51

Proteolytic activation of inactive proteases (zymogens)

Question 52

What converts prothrombin to thrombin?

Answer 52

Factor Xa

Question 53

What is prothrombin?

Answer 53

An inactive protease (zymogen)

Question 54

What is thrombin?

Answer 54

An active protease?