Lecture 31: Gluconeogenesis and the Pentose Phosphate Pathway

Question 1

What happens when glucose levels are low in animals?

Answer 1

Gluconeogenesis occurs and glucose is released from the liver

Question 2

What happens when glucose levels are low in plants?

Answer 2

Glucose is made through a combination of PPP and gluconeogenesis

Question 3

What to anabolic processes that convert glucose to pyruvate use?

Answer 3

ATP and GTP

Question 4

How many irreversible steps does glycolysis have?

Answer 4

3

Question 5

for reversible and irreversible steps, what does ΔG depend on?

Answer 5

ΔG depends on ΔGo’ and q

Question 6

Reversible steps:
ΔG close to 0 so changes in q controls direction of reaction

Answer 6

Irreversible steps:ΔG &laquo_space;0 so physiological changes in q not big enough to reverse reaction

Question 7

Is itr true that ‘steps with large negative ΔG are irreversible under physiological conditions and hence often used as regulatory steps’?

Answer 7

Yes

Question 8

Are reversible steps shared in 2 opposing pathways good for regulation?

Answer 8

No

Question 9

How is glucose made in gluconeogenesis?

Answer 9

Glucose-6-P + H2O → Glucose + Pi

Question 10

How is F-6-P made in gluconeogenesis?

Answer 10

F-1,6-bisP + H2O → F-6-P + Pi

Question 11

why isn’t ATP regenerated in gluconeogenesis?

Answer 11

Because it isn’t simply a reversal of the steps in glycolysis

Question 12

Futile cycles

Answer 12

• losing ATP
• Not really gaining anything from running the 2 cycles at the same time
• Fructose-6-P + ATP → Fructose-1,6-bisP + ADP

Fructose-1,6-bisP + H2O → Fructose-6-P + Pi

Net: ATP + H2O → ADP + Pi

(Metabolic pathways tightly regulated to avoid futile cycles
PFK and Fructose-1,6-bisphosphatase both tightly
and oppositely regulated, so that only one reaction runs at a time
)

Question 13

What is the last step (irreversible) of glycolysis?

Answer 13

PEP + ADP → pyruvate and ATP

Question 14

Draw out the structure of pyruvate

Question 15

Glycolysis

Pyruvate -> Oxaloacetate -> PEP

Question 16

What is the starting material for pyruvate?

Answer 16

Lactate

Some amino
acids

Question 17

What is the starting material for Oxaloacetate?

Answer 17

Some amino acids

Question 18

Is oxaloacetate a citric acid intermediate?

Answer 18

Yes

Question 19

What is the starting material for Dihydroxyacetone?

Answer 19

Even though fats can’t normally be turned into glucose, glycerol

Question 20

Where in the cell does gluconeogenesis occur?

Answer 20

In the cytosol (cytoplasm)

Question 21

Is gluconeogenesis a linear or branched pathway?

Answer 21

Linear

Question 22

What are the entry points for gluconeogenesis?

Answer 22

Pyruvate, oxaloacetate, glyceraldehyde-3P

Question 23

What is the end point of gluconeogenesis?

Answer 23

Glucose

Question 24

What other pathway is gluconeogenesis linked to?

Answer 24

Pentose phosphate pathway and others

Question 25

How many steps does gluconeogenesis have?

Answer 25

11 steps, most shared with glycolysis

Question 26

How is gluconeogenesis regulated?

Answer 26

Oppositely to glycolysis

Question 27

Apart from pyruvate, what can also generate acetyl coA?

Answer 27

Fatty acids and ketogenic amino acids

Question 28

Can glucose be metabolised into ribose?

Answer 28

Yes

Question 29

Does NADPH have any relevance in ATP regeneration?

Answer 29

No

Question 30

What is NADP essential fr?

Answer 30

reductive biosynthesis and reducing oxidative stress (antioxidant)

Question 31

Does NAD help make ATP?

Answer 31

Yes

Question 32

Do NAD and NADP have opposite roles?

Answer 32

Yes

Question 33

What is the Pentose phosphate pathway?

Answer 33

The sequence of reactions that converts glucose to pentoses (then to hexoses and trioses) with the production of NADPH

Question 34

What is the pentose Ribose-5-P needed for?

Answer 34

Ribose-5-P needed for DNA and RNA (and ATP, NAD+, FAD, CoA) synthesis

Question 35

What are the 2 main functions of the pentose phosphate pathway?

Answer 35

Producing NADP and producing Ribose-5-Phosphate

Question 36

What are the 2 different stages of the pentose phosphate pathway?

Answer 36

• The oxidative stage, where the NADPH is being generated.
• The non-oxidative stage, where ribose-5-P and glycolytic intermediates are generated.

Question 37

Draw out a diagram of the pentose phosphate pathway

Question 38

Describe the oxidative steps of the pentose phosphate pathway

Answer 38

• Glucose 6-P → Ribulose 5-P + CO2
• Strategy: oxidise glucose, then oxidatively decarboxylate. NADP+ is the electron acceptor for both steps
• Step 1: Glucose 6-P Dehydrogenase
  oxidises to an intramolecular ester
  forms NADPH
  control step
• Step 2: Gluconolactonase
  hydrolyses intramolecular ester. From ring structure to chain carboxylic acid.
• Step 3: 6-P gluconate DH
  oxidatively decarboxylates releasing CO2.
  forms NADPH. G-6-P to ribulose-5-P giving 2 NAPDH

Question 39

Non oxidative stage

Answer 39

• Ribulose 5-P → Ribose 5-P
• Via a ketose - aldose isomerisation (Similar to G-6-P/F-6-P interconversion in glycolysis
  )
• Ribose can be removed and used to make DNA/RNA OR Ribulose can be recycled to glucose

-

Question 40

Carbohydrate interconversions to form G-6-P

3 Ribulose-5-P → 2 F-6-P + 1 G-3-P → (2.5) G-6-P

Gluconeogeneis can then be used to regenerate glucose

Answer 40

These reactions are reversible i.e. controlled by availability of substrates

Question 41

What type of pathway is the pentose phosphate pathway?

Answer 41

A cyclic pathway

Question 42

Describe the 4 different modes of the pnetose phosphate pathway

Answer 42

No NADPH production, G-6-P converted to ribose (when no reductive biosyntheiss needed i.e n fatyy acids needed)

Production of both NADPH and ribose

NADPH needed but no ribose

Cells need NADPH and ATP

Question 43

Describe mode 1

Answer 43

• Maximises ribose-5-P production
• Occurs in rapidly dividing cells that need lots of DNA and RNA
• Carbohydrate interconversions (in reverse)
• Non-oxidative stage run backwards
• Starts from glycolytic intermediates
• No oxidative stage , Hence, no NADPH production

Question 44

Describe mode 2

Answer 44

• Cells need both ribose-5-P and NADH
• Can occur in most cells under appropriate physiological conditions
• G-6-P is converted to R-5-P
• Only oxidative stage is running
• 2 NADPH per glucose

Question 45

Describe mode 3

Answer 45

• NADPH is needed but not ribose-5-P
• Occurs in adipose tissue or red blood cells
• G-6-P is completely oxidised to CO2
• Cyclic mode
• 12 NADPH per glucose

Question 46

Describe mode 4

Answer 46

• Cells need NADPH and ATP
• Occurs in most cells under appropriate physiological conditions
• Like Mode 3, but glycolytic intermediates are used for energy production, not in gluconeogenesis

Question 47

Favism

Answer 47

Recessive X-linked disorder

Causes Hemolytic anemia when eating fava beans and sometimes other legumes

Hemolytic anemia will also be seen when they take other types of drugs

Hemolytic anemia is when the red blood cells burst

This is due to Glucose-6-P dehydrogenase deficiency, i.e. the PPP
pathway is compromised

Favism compromises NADPH but not ribose-5-P production via mode 1

NADPH reduces oxidative stress

Red blood cells dependent on PPP to reduce oxidative stress

Red blood cells exposed to oxidative stress are prone to hemolysis

Deficiency is benign when no oxidative stress

Question 48

Which enzyme catalyses the first step in the pentose phosphate pathway? (key regulatory enzyme for oxidative stage)

Answer 48

Glucose-6-P dehydrogenase / oxidative stage