Glycolysis

Question 1

Represent the three most abundant six-carbon sugars in most people’s diets

Answer 1

Glucose, Fructose, and Galactose

Question 2

Because of their structural similarity, fructose and galactose metabolism are able to integrate into

-only requires a few enzymatic steps

Answer 2

Glucose Metabolism

Question 3

The bulk of glucose’s chemical energy remains untapped as glycolysis ends with the formation of

Answer 3

Pyruvate

Question 4

Fully oxidized to CO2 and H2O in the citric acid cycle

Answer 4

Pyruvate

Question 5

The conversion of glucose to pyruvate takes place in which two stages?

Answer 5

1. ) Energy investment stage

2. ) Energy generation stage

Question 6

While in the energy investment stage phosphorylated intermediates are made at the expense of

Answer 6

ATP

Question 7

In the energy generation phase, substrate level phosphorylation generates how many ATP per glucose molecule?

Answer 7

2

Question 8

At the end of glycolysis, we also see the production of

Answer 8

2 NADH

Question 9

In the first stage of glucose metabolism, two high-energy ATP molecules are consumed in the production of

Answer 9

Fructose 1,6-bisphosphate

Question 10

This ‘energy investment’ phase includes two of the 3 enzymatic steps critical to regulation of flux through glycolysis, both of which are

Answer 10

Phosphorylation reactions

Question 11

Highly hydrophilic compounds, unable to diffuse passively across the hydrophobic barrier of the cytoplasmic membrane

Answer 11

Sugars

Question 12

Function to move glucose down its concentration gradient into the interior of the cell

Answer 12

GLUT1-GLUT5

Question 13

Primarily involved in glucose uptake from the blood

Answer 13

GLUT1, GLUT3, and GLUT4

Question 14

Found in the liver, kidney and pancreas, and can transport glucose into and out of cells

Answer 14

GLUT2

Question 15

Allows for insulin regulated uptake and storage of glucose in fat and muscle during times of sufficient blood glucose

Answer 15

GLUT4 insulin sensitivity

Question 16

Recall that a low Km value implies

Answer 16

High receptor affinity for a substrate

Question 17

Have low Km values and no insulin sensitivity to insure a constant basal uptake of glucose

Answer 17

GLUT1 and GLUT3

Question 18

Has a higher Km, and will more easily take in glucose during periods of high blood glucose

Answer 18

GLUT2

Question 19

In Pancreatic B cells this GLUT-2 mediated uptake results in insulin secretion which allows the activation of

Answer 19

GLUT4

Question 20

Has a lower Km then GLUT-2, and will insure that skeletal and adipose tissue extract glucose from the blood faster than the liver

Answer 20

GLUT4

Question 21

Unusual in that it is the primary transporter for fructose (instead of glucose) in the small intestine and the testes

Answer 21

GLUT5

Question 22

Phosphorylation of intracellular glucose helps to maintain a ‘downhill’ gradient of sugar from outside to inside the cell, and it traps the phosphorylated sugar

Answer 22

Inside of the cell

Question 23

The first covalent modification to intracellular glucose is the addition of a phosphate onto the #6 carbon, making

Answer 23

Glucose-6-phosphate (G-6-P)

Question 24

This reaction is catalyzed by one of two enzymes, depending upon the tissue in question. These are referred to as

Answer 24

Isoenzymes

Question 25

Functions in most tissues, and has a low Km and a low Vmax, but a broad specificity for six carbon sugars

Answer 25

Hexokinase

Question 26

Located in the liver and in the pancreas, and has a high Km and a high Vmax

Answer 26

Glucokinase

Question 27

Permits the liver to respond to high concentrations of blood sugar that are obtained following a meal

Answer 27

The high Km of glucokinase in the liver

Question 28

Plays a central role in the regulation of blood glucose, and this capacity of glucokinase helps it to diminish the hyperglycemia that follows a meal

Answer 28

Liver

Question 29

Serves peripheral tissues by permitting them to metabolize only the quantity of glucose that meets their immediate needs, but also to be able to do so efficiently, even at lower blood glucose concentrations

Answer 29

Low Km of Hexokinase

Question 30

Consistent with this role hexokinase expression is not effected by

Answer 30

Insulin

Question 31

Importantly, high levels of G6P inhibit

Answer 31

Hexokinase

Question 32

Glucokinase is not inhibited by its product, but it is inhibited by -Binds to the glucokinase regulatory protein

Answer 32

Fructose 6-phosphate

Question 33

This inhibition is reversed under conditions either of high intracellular glucose or

Answer 33

Fructose-1-phosphate

Question 34

Glucokinase expression is positively influenced by

Answer 34

Insulin

Question 35

GLUT-1 & 3 expressing cells insure a steady input of glucose into the cytosol where it can be “secured” by phosphorylation via

Answer 35

Hexokinase (which also has a low Km)

Question 36

This process is inhibited in times of glucose excess by -Ensures that cells do not make more glucose than metabolically necessary

Answer 36

G6P

Question 37

A similar rationale can be seen with the GLUT-2 expressing liver. During glucose excess insulin will trigger increased

Answer 37

Glucokinase Expression

Question 38

Because glucokinase does not have feedback inhibition it will be able to take in excess glucose even though its transporter and glucokinase have higher

Answer 38

Km's

Question 39

Regardless of which kinase is used, synthesis of glucose 6 phosphate from glucose and ATP is an

Answer 39

Irreversible Reaction

Question 40

Following the isomerization of glucose 6-phosphate to fructose 6-phosphate, a second, tightly regulated, phosphorylation takes place, catalyzed by the enzyme

Answer 40

Phosphofructokinase-1 (PFK-1)

Question 41

This Reaction catalyzed by PFK-1 produces

Answer 41

Fructose 1,6-bisphosphate

Question 42

The most influential and regulatory step in glycolysis

Answer 42

The PFK-1 production of F-1,6-BP

Question 43

The PFK-1 production of F-1,6-BP is an

Answer 43

Irreversible reaction

Question 44

PFK-1 is negatively regulated by

Answer 44

ATP and Citrate

Question 45

This is logical as both of these compounds, when present in the cell at high concentrations, are indicative of an

Answer 45

Energy Rich State

Question 46

PFK-1 is also inhibited by

Answer 46

Low pH

Question 47

PFK-1 is POSITIVELY regulated by

Answer 47

AMP and Fructose-2,6-BP

Question 48

An allosteric activator of PFK-1

Answer 48

Fructose-2,6-BP

Question 49

Intracellular levels of fructose 2,6-bisphosphate are altered by the variable action of a dual function enzyme called

Answer 49

PFK-2/FBP-2

Question 50

PFK-2/FBP-2 has two different

Answer 50

Catalytic activities

Question 51

Responsible for the synthesis of fructose 2,6-bisphosphate, from fructose 6-phosphate and ATP

Answer 51

PFK-2 (a kinase)

Question 52

Catalyzes essentially the reverse of this reaction, production of fructose 6 phosphate and Pi from fructose 2,6-bisphosphate

Answer 52

FBP-2 (a phosphatase)

Question 53

The PFK-2/FBP-2 itself is regulated by

Answer 53

Phosphorylation or Dephosphorylation

Question 54

Signal transduction cascades beginning with insulin and glucagon, on cellular membrane receptors, and ending with protein kinase and phosphatase activities regulate

Answer 54

Phosphorylation and dephosphorylation of PFK-2/FBP-2

Question 55

During the well-fed state, glucagon levels decrease and insulin levels rise. These changes lead to

Answer 55

Dephosphorylation of PFK-2/FBP-2

Question 56

Dephosphorylation of PFK-2/FBP-2 leads to active -hence more Fructose-2,6-BP

Answer 56

PFK-2

Question 57

Elevated levels of fructose 2,6-bisphosphate activate

Answer 57

PFK-1

Question 58

Thus the rate of glycolysis in the liver is

Answer 58

Increased

Question 59

Fructose 2,6-bisphosphate acts as an intracellular signal, indicating that glucose is

Answer 59

Abundant

Question 60

During fasting and starvation, glucagon levels rise and insulin levels decrease. These changes lead to

Answer 60

Phosphorylation of PFK-2

Question 61

This leads to an inactivation of

Answer 61

PFK-2

Question 62

Reduced levels of fructose 2,6-bisphosphate inhibit the activity of PFK-1, thus the rate of

Answer 62

Liver glycolysis

Question 63

Subject to regulation on a local, intracellular level via ATP, AMP, H+, and citrate, small molecule indicators of the local and immediate metabolic/physiologic state

Answer 63

PFK-1

Question 64

Also subject to regulation on a larger, organ scale via insulin and glucagon, with fructose 2,6-bisphosphate as an intermediary

Answer 64

PFK-1

Question 65

Splits fructose 1,6 bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate

Answer 65

Aldolase A

Question 66

Catalyzes the interconversion of these three-carbon compounds

Answer 66

Triose Phosphate Isomerase

Question 67

Glyceraldehyde 3-phosphate is then recruited by glyceraldehyde 3-phosphate dehydrogenase to produce

Answer 67

1,3-BPG

Question 68

This intermediate leads to the first production of

Answer 68

ATP

Question 69

Action of the isomerase permits us to start with one molecule of glucose, and proceed on with two molecules of

Answer 69

1,3-BPG

Question 70

Take note that in order to oxidize glyceraldehyde 3-phosphate, glyceraldehyde 3-phosphate dehydrogenase requires

Answer 70

NAD+

Question 71

The phosphate on carbon #1 of 1,3 bisphosphoglycerate is transferred to

Answer 71

ADP

Question 72

The phosphate on carbon #1 of 1,3 bisphosphoglycerate is transferred to ADP by -produces ATP and phosphoglycerate

Answer 72

Phosphoglycerate Kinase

Question 73

This reaction is

Answer 73

Reversible

Question 74

3-phosphoglycerate is ocnverted into 2-phosphoglycerate by -Reversible and unregulated

Answer 74

Phosphoglycerate Mutase

Question 75

Converts 2-phosphoglycerate into phosphoenolpyruvate, with the release of one molecule of water

Answer 75

Enolase

Question 76

Participates in the second substrate level phosphorylation in glycolysis, and the production of a second ATP molecule

Answer 76

Phosphoenolpyruvate

Question 77

Dephosphorylates phosphoenolpyruvate, producing ATP and pyruvate -An IRREVERSIBLE reaction

Answer 77

Pyruvate Kinase

Question 78

Regulation of this step takes a somewhat unusual form. Fructose 1,6-bisphosphate acts in a feed-forward manner to stimulate

Answer 78

Pyruvate Kinase

Question 79

Liver pyruvate kinase is itself subject to direct phosphorylation, causing

Answer 79

Inactivation

Question 80

The phosphorylation (inctivation) and Dephosphorylation (activation) of pyruvate kinase is mediated by

Answer 80

Glucagon and Insulin respectively

Question 81

The decreased breakdown of PEP is also helpful during glucagon-induced

Answer 81

Gluconeogenesis

Question 82

Subject to local, intracellular regulation by fructose 1,6 bisphosphate and it’s also subject to higher order regulation via protein phosphorylation/dephosphorylation and the hormones insulin and glucagon

Answer 82

Pyruvate Kinase

Question 83

Glycolysis will come to a halt without the ability to recycle

Answer 83

NADH to NAD+

Question 84

What are the two mechanisms by which cells can replenish NAD levels?

Answer 84

1. ) Oxidative phosphorylation | 2. ) Conversion of Pyruvate to Lactate

Question 85

Without oxidative phosphorylation, the cell converts pyruvate to lactate using

Answer 85

Lactate dehydrogenase

Question 86

The conversion of pyruvate to lactate by lactate dehydrogenase also does what?

Answer 86

Oxidizes NADH to NAD+

Question 87

If rates of production exceed blood-mediate clearance, high levels of lactate can drop the

Answer 87

Local pH

Question 88

The cramping that occurs during heavy exercise is the consequence of rapid local production of

Answer 88

Lactate

Question 89

Lactate is eventually taken up by liver, via the circulatory system, and re-converted to pyruvate via the reversible lactate dehydrogenase reaction. This muscle/blood/liver handoff has been designated the

Answer 89

Cori Cycle

Question 90

The process of oxidative phosphorylation is able to take each NADH produced in aerobic glycolysis and generate

Answer 90

3 ATP

Question 91

Which produces more ATP per glucose molecule, aerobic or anaerobic glycolysis?

Answer 91

Aerobic

Question 92

What are the three enzymes that catalyze the three irreversible reactions in glycolysis?

Answer 92

Gluco/Hexokinase, PFK-1, and pyruvate kinase

Question 93

We see feedback inhibition of hexokinase by

Answer 93

G6P

Question 94

Neither insulin nor glucagon actually enters the cells that are responsive to

Answer 94

Them

Question 95

Glucagon signaling typically stimulates

Answer 95

Phosphorylation

Question 96

Insulin signaling typically stimulates

Answer 96

Dephorphorylation

Question 97

Leads to disruption of glycolysis and the build up of glycolytic intermediates

Answer 97

Pyruvate Kinase Deficiency

Question 98

Cell dehydration, contraction, and crenation (echinocytes), leading to premature destruction of the erythrocyte are a sign/symptom of

Answer 98

Pyruvate Kinase deficiency

Question 99

An Increased offloading of O2 into tissues due to increased 2,3-BPG is a sign/symptom of -results in improved exercise performance in these patients relative to others with similarly low Hgb

Answer 99

Pyruvate kinase deficiency

Question 100

How can we treat the hemolytic anemia seen with pyruvate kinase deficiency?

Answer 100

Transfusions, supplemental folic acid, splenectomy