Lecture 27: Pentose Phosphate Pathway

Question 1

Why do we need NADPH

Answer 1

Synthesis of monomers
-Fatty acids
-Cholesterol
-Neurotransmitters
-Nucleotides
Reducing powers

Question 2

Lactonase is what type of enzyme

Answer 2

Hydrolase

Question 3

What is the rate limiting reaction in the oxidative phase of PPP

Answer 3

G6P–> Lactone (not specified which one)

Catalyzed by G6P dehydrogenase

Question 4

Glutathione is a tripeptide of what amino acids

Answer 4

Glutamic acid
Cysteine
Glycine

Question 5

Why is glutathione able to interact with proteins without an enzyme

Answer 5

Because of its disulfide bonds?

Question 6

What is required for reduction of Glutathione

Answer 6

NADPH

Question 7

Ratio of reduced Glutathione (GSH) to oxidized glutathione (GSSG) in normal cell

Answer 7

500:1

Question 8

What other proteins besides G6PD can make NADPH

Answer 8

Isocitrate dehydrogenase

Malic enzyme

Question 9

What is the most severe effect of G6PD deficiency

Answer 9

Liver cannot conjugate bilirubin, excessive amounts of bilirubin causes jaundice

Question 10

G6PD can be a monomer, dimer and tetramer- which states are active/inactive, and what conditions favor those states

Answer 10

Monomer- Inactive- High NADPH, G6P, pH
Dimer- Active- High ionic strength, pH >8
Tetramer- Active- High NADP+, pH <6

Question 11

Hsp27 interaction with G6PD

Answer 11

Promotes dimerization/activation

Question 12

Activators of G6PD include

Answer 12

Dimerization
Transcription factors for antioxidant genes
Cell cycle and synthesis activators
Insulin

Question 13

Inhibitors of G6PD include

Answer 13

Phosphorylation

Apoptosis-signaling proteins

Question 14

The non oxidative phase of the PPP shuffles

Answer 14

Carbons

Question 15

Ribose-5-phosphate isomerase

Answer 15

Part of shuffle 1

Converts Ribulose-5-phosphate to Ribose-5-phosphate

Question 16

Ribulose-5-phosphate epimerase

Answer 16

Part of shuffle 1

Converts Ribulose-5-phosphate to Xylulose-5-phosphate

Question 17

Transketolase

Answer 17

Shuffle 2
Transfers 2C from X5P, leaving behind Glyceraldehyde-3-phosphate
2C + Ribose-5-Phosphate–>Sedoheptulose-7-phosphate
2C + Erythrose-4-phosphate–> F6P
Transition state stabilized by TPP coenzyme

Question 18

Transaldolase

Answer 18

Shuffle 3
Transfers 3C from Sedoheptulose-7-phosphate leaving behind Erythrose-4-phosphate
3C + Glyceraldehyde-3-phosphate –> F6P
Transition state stabilized by Lysine side chain

Question 19

Shuffle 4, the final phase of the non-oxidative phase, regenerates what molecule using what pathway

Answer 19

Regenerates Glucose-6-Phosphate using gluconeogenesis pathway

Question 20

Nucleotide synthesis mode

Answer 20

Nonoxidative mode in reverse

G3P and F6P both used to make Ribose-5-Phosphate

Question 21

Balancing nucleotides and NADPH

Answer 21

G6P is converted to Ribose-5-Phosphate and NADPH is made

Question 22

Anabolic needs

Answer 22

When primary need is for reducing power, fructose phosphates are converted into G6P for reoxidation in the oxidative phase
Primary product is NADPH

Question 23

More power phase

Answer 23

When primary need is power and not much NADPH/pentose phosphates are needed, the reaction products (Gly-3-P) are used in glycolysis and Citric acid cycle

Question 24

Why are G6PDD patients more likely to develop diabetes

Answer 24

Because high blood glucose levels will decrease expression of G6PD in pancreatic b-islet cells which produce insulin.

Question 25

Which phase of PPP will be used if the cell needs NADPH as much as it needs R5P?

Answer 25

Oxidative phase only

Question 26

If a cell is beginning to divide/replicate, which phase will be used

Answer 26

F6P and G3P go through reverse steps of non-oxidative phase of PPP to build R5P

Question 27

In an adipose cell that is constantly building fatty acids, which phase/pathway will be used

Answer 27

Oxidative and non-oxidative steps will be performed

Gluconeogenesis will then be used to recycle F6P and G3P back to G6P in order to re-enter oxidative phase.

Question 28

What pathways are used if the cell needs both ATP and NADPH

Answer 28

Oxidative and non-oxidative phase both used

Glycolytic intermediates GAP and F6P enter glycolysis for ATP and pyruvate formation