Gluconeogenesis, glycogen metabolism and the PPP

Question 1

What are the uses of glucose?

Answer 1

• storage
• growth
• glycolysis

Question 2

Memorise glycolysis/glyconeogenesis diagram

Answer 2

(slide 3)

Question 3

What is the pentose phosphate pathway (PPP)?

Answer 3

A metabolic process that generates:
- NADPH
- pentose (5-carbon sugars)

Question 4

What are the 2 phases of PPP?

Answer 4

• oxidative phase
• non-oxidative

Question 5

What does the oxidative phase of PPP generate?

Answer 5

• 2 molecules of NADPH (used as reducing power in fat synthesis)
• ribose-5-phosphate for DNA & RNA synthesis

Question 6

Describe the steps of the oxidative phase of PPP

Answer 6

glucose 6-phosphate

↓ (G-6P dehydrogenase)

6-phosphoglucono-δ-lactone

↓ (lactonase)

6-phosphogluconate

↓ (6-phosphogluconate DH)

ribulose 5-phosphate

↓ (phosphopentase isomerase)

ribose 5-phosphate

Question 7

What does the non-oxidative phase of PPP generate?

Answer 7

3 ribose-5-phosphate → 2 fructose-6-phosphate + glyceraldehyde 3-phosphate

3 C5 → 2 C6 + C3

Question 8

When does the non-oxidative phase of PPP occur?

Answer 8

• if the pentose (C5) sugars are not required
• then the non-oxidative phase allows for the sugars to be converted
• into glycolytic or gluconeogenic intermediates

Question 9

Where is glucose-6-phosphate
dehydrogenase (G6PDH) from the oxidative phase found?

Answer 9

• G6PDH found on the X-chromosome
• expressed almost exclusively in red blood cells; only enzyme to reduce NADP+

Question 10

What does a deficiency of G6PDH cause?

Answer 10

Haemolytic anaemia
- 400 million people affected
- many variants → different severity, but no null mutants (lethal)
- only red blood cells affected as other cells have H6PDH (hexose…)

Question 11

What is gluconeogenesis?

Answer 11

the formation of new glucose

Question 12

What is the overall equation of gluconeogenesis?

Answer 12

2 NADH + 4 ATP + 2 GTP + 2 Pyruvate + 6 H20 + 2 H+
→ Glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi

Question 13

What is Pi?

Answer 13

inorganic phosphate

Question 14

What is our main gluconeogenic tissue?

Answer 14

liver

Question 15

How is glucose made during/after anaerobic respiration?

Answer 15

pyruvate / lactate from muscle is converted to glucose by liver

Question 16

What reactions does the Cori cycle involve?

Answer 16

• glycolysis
• gluconeogenesis

Question 17

What 3 main reactions (in glycolysis) need to be reversed for gluconeogenesis?

Answer 17

3 bypass reactions:
- phosphoenolpyruvate → pyruvate
- fructose 6-phosphate → fructose 1,6-biphosphate
- glucose → glucose 6-phosphate

Question 18

What happens in the bypass reaction 1?

Answer 18

• NB needs energy input (4 ATP equivalents per glucose formed)
• reverses pyruvate kinase reaction in glycolysis

Question 19

Where does the 1st bypass reaction occur?

Answer 19

• first part of reaction happens in mito matrix
• second in cytoplasm
• oxaloacetate cannot pass through inner mitochondrial membrane (IMM)
• solution = malate shuttle
  (slide 17)

Question 20

What is a malate shuttle?

Answer 20

• mechanism that transports NADH molecules produced in glycolysis into the mitochondrial matrix
• to reduce oxaloacetate into malate

Question 21

What happens in the bypass reaction 2?

Answer 21

negative bicarbonate (NB) cannot make ATP as not a high energy phosphate bond

Question 22

What happens in the bypass reaction 3?

Answer 22

NB cannot make ATP as not a high energy phosphate bond

Question 23

Why can’t all cells bypass reaction 3?

Answer 23

• not all cells have G-6-Pase

Question 24

What are the gluconeogenesis substrates?

Answer 24

• protein
• lactate
• glycerol

Question 25

What is a disease of gluconeogenesis?

Answer 25

Von Gierke’s Disease - Type I glycogen storage disease (GSD)