Week 8: Glycolysis, Gluconeogensis, and Pyruvate Dehydrogenase Complex

Question 1

What sign is an irreversible reaction

Answer 1

Negative Delta G
Spontaneous

Question 2

How long does gene level control enzymes take

Answer 2

Hours

Question 3

How long does covalent modification (Phosphorylation, Methylation)

Answer 3

In seconds

Question 4

How long does Allosteric Regulation

Answer 4

Milliseconds

Question 5

3 Enzymes that are control enzymes in glycolysis

Answer 5

Step 1 - Hexokinase, add P to #6C on glucose
Step 3 - Phosphofructokinase, add 2nd P to F-1,6
Step 9 - Pyruvate Kinase, add P to ADP from Phosphoenolpyruvate

Question 6

What is the committed step in glycolysis

Answer 6

PFK

Question 7

Muscle Mechanisms

Answer 7

Energy

Question 8

Liver Mechanisms

Answer 8

Energy and biosynthesis
From amino acids and fatty acids

Question 9

Muscle process in glycolysis is due to what ratio

Answer 9

Regulation of glycolysis in muscle is mostly due to energy charge = ATP/AMP

Question 10

What is ATP to PFK and Pyruvate Kinase

Answer 10

It is a negative effector

Question 11

What is the key regulator of glycolysis in mammals

Answer 11

PFK

Question 12

What does ATP and AMP to cells

Answer 12

Allosterically inhibited by ATP and Allosterically stimulated by AMP

Question 13

How is the entire pathway regulated

Answer 13

1.) Energy Charge
2.) Feedback

Question 14

When ATP needs are great how does the body compensate

Answer 14

Adenylate Cyclase generates ATP from 2ADP

Question 15

Liver: Key regulators

Answer 15

Key Regulators are
Citrate (reports on status of CAC)
Fructose 2,6-Bisphopahte

Question 16

What does citrate and F-2,6-BP due to PFK

Answer 16

Citrate inhibits PFK
F-2,6-BP activates PFK

Question 17

What does high citrate concentration due

Answer 17

Plenty of biomaterial to work with, high citrate then slows down glycolysis because less glucose is needed

Question 18

Name two Bifunctional Enzyme

Answer 18

PFK-Kinase
FBP-Phosphatase

Question 19

What kind of enzyme is hexokinase

Answer 19

Allosteric

Question 20

How is Pyruvate Kinase regulated in liver as in muscle

Answer 20

Allosterically

Question 21

In liver how is Pyruvate Kinase also regulated

Answer 21

Covalent Modification

Question 22

What does low blood glucose lead to

Answer 22

Phosphorylation and inhibition of liver pyruvate kinase

Question 23

Glucagon

Answer 23

Hormone that stats phosphorylation cascade that ends up phosphorylating pyruvate kinase

Question 24

How many steps in Gluconeogensis

Answer 24

Pyruvate - Glucose in 11 steps
7 of them are the same as in glycolysis

Question 25

Where does Gluconeogensis happen

Answer 25

Major site in liver, but can also happen in the kidney

Question 26

When is Gluconeogensis important

Answer 26

Important during tasting or starvation - glucose is primary fuel for the brain and only fuel for red blood cells

Question 27

How can pyruvate be from in the liver

Answer 27

Can be formed from lactate in the liver by lactate dehydrogenase. Then pyruvate can make glucose

Question 28

What can Carbon skeltons be converted to

Answer 28

Carbon skeleton of amino acids can be converted to gluconeogenic intermediates

Question 29

How is glycerol derived

Answer 29

Gylcerol, derived from hydrolysis of triacylglycerols, can be converted to dihydroxyaceton phosphate, which can be used in both glycolysis and gluconeogensis

Question 30

Step 1 of Gluconeogensis

Answer 30

Step 1 - Pyruvate Carboxylase Reaction Requires pyruvate carboxylase (in mitochondria) and PEP carboxykinase (cytoplasm) Pyruvate - Oxaloacetate occurs in 3 steps Requires biotin as a cofactor carries carboxylate groups (COO)

Question 31

Step 2 - Phosphoenolpyruvate Carboxykinase

Answer 31

Oxaloacetate moved to cytoplasm before this step

Question 32

Step 9 - Fructose-1,6-Bisphosphatase

Answer 32

Takes off phosphate Allosteric enzyme is the control point

Question 33

Step 11 - Glucose 6-Phosphate

Answer 33

Glucose 6-Phosphate transported to the ER Glucose 6-Phosphatase, Integral membrane enzyme on surface of ER, catalyzes Glucose 6-P to Glucose

Question 34

What remains the same from glycolysis to gluconeogensis

Answer 34

Steps 3-8 Step 10: Isomerase

Question 35

Why don't glycolysis and gluconeogensis run in reverse

Answer 35

Both glycolysis and gluconeogensis have control points with different ezymes, that are unidirectional (irreversible) Steps 1,3,9 - Regulatory steps in glycolysis Steps 1,2,9,11 - Regulatory steps in gluconeogensis

Question 36

What are the key regulator of glucose metabolism

Answer 36

Fructose-2,6-Bisphosphate stimulates glycolysis and inhibits gluconeogensis

Question 37

What is F-2,6-BP synthesized by and hydrolyzed by

Answer 37

Phosphofructokinase 2 (PFK 2) Fructose Bisphoshatase 2

Question 38

Are they on the same peptide chain

Answer 38

Yes, bifunctional enzyme

Question 39

What is released when blood glucose levels are low

Answer 39

The hormonne glucagon is secreted by the pancreas

Question 40

What does the glucagon pathway lead to and what does it inhibit and stimulate

Answer 40

Leads to phosphorylation of the bifunctional enzyme Inhibits kinase Stimulates phosphatase

Question 41

Pyruvate Dehydrogenase

Answer 41

Critical link between glycolysis and citric acid cycle

Question 42

What does the synthesis of Acetyl CoA from pyruvate require

Answer 42

Requires 3 enzymes and 5 coenzymes (All the pyruvate dehydrogenase complex)

Question 43

The 3 steps in Pyruvate Dehydrogenase Complex

Answer 43

Decarboxylation Oxidation Transfer to CoA

Question 44

The 3 enzymes in pyruvate dehydrogenase complex

Answer 44

E1: TPP E2: Lipoamide E3: FAD

Question 45

E1-TPP Enzyme Reaction Catalyzed

Answer 45

Pyruvate Dehydrogenase Component Oxidative decarboxylation of pyruvate

Question 46

E2-Lipoamide Enzyme Reaction Catalyzed

Answer 46

Dihydrolipoyl Transacetylase Transfer of Acetyl group to CoA

Question 47

E3-FAD Enzyme Reaction Catalyzed

Answer 47

Dihydrolipoyl Dehydrogenase Regeneration of the oxidized form of lipoamide

Question 48

How can lipoamide move between different active sites

Answer 48

Flexible linkages "Swinging arm"

Question 49

How many enzymes are structurally integrates, and what enzyme does move

Answer 49

3 enzymes Lipoamide arm allows rapid movement of substrates and products from one active site of the complex to another

Question 50

Steps of Complex Action

Answer 50

1. Binding to TPP cofactor 2. E2 inserts lipoamide into E1 3. Transfer of acetyl group onto lipoamide goes to E2 active site 4. Transfer of acetly group to CoA 5. Lipoamide is oxidized by FAD 6. FAD is oxidized by NAD+

Question 51

Is the formation of Acetyl CoA from pyruvate reversible or irreversible

Answer 51

Irreversible

Question 52

Where does Acetyl CoA go

Answer 52

Either Citric Acid Cycle or incorporation into fatty acid

Question 53

Out of the 3 E enzymes what is the key site of regulation

Answer 53

E1 Covalent modification

Question 54

What activates E1 enzyme

Answer 54

Phosphatase attached that removes the phosphate and thus activates the enzyme

Question 55

Is E1 allosteric

Answer 55

Yes

Question 56

What inhibits E1 comples

Answer 56

ATP Acetyl CoA NADH

Question 57

What stimulates the complex

Answer 57

ADP Pyruvate

Question 58

Is a single large complex an advantage

Answer 58

Yes

Question 59

How is reaction facilitated

Answer 59

Facilitated by having active sites in close proximity

Question 60

When do reactants leave enzyme

Answer 60

Not until final product is made limits side reaction A more tightly controlled enzymatic mechanism

Question 61

What do all enzymes need to do

Answer 61

Need to exist in the proper amount because the entire thing is made together

Question 62

How is regulation efficient

Answer 62

Regulation is more effecient because regulatory enzymes are also a part of the complex