Gluconeogenesis & Pentose Phosphate Pathway

Question 1

What is the purpose of gluconeogenesis? Where does it occur and what are its substrates?

Answer 1

Synthesize glucose, specifically during prolonged fasting

Occurs in liver and kidney

Main substrates are pyruvate, oxaloacetate, and glycerol

Question 2

When is gluconeogenesis most active?

Answer 2

During fasting when insulin is low and glucagon is high

Question 3

What cycle is gluconeogenesis also part of?

Answer 3

Cori Cycle - converts lactate back to glucose

Question 4

Fructose 1,6 bisphosphatase deficiency

Answer 4

Gluconeogenesis disorder

Pt presents with fasting hypoglycemia and metabolic acidosis. Liver shows fat deposits and pt has abnormal glucagon response, elevated serum lactate, pyruvate, and alanine during hypoglycemia

Question 5

What general symptoms do patients with a gluconeogenesis disorder present with? Why?

Answer 5

1. Fasting hypoglycemia - impaired glucose production
2. Metabolic acidosis - accumulation of lactate, pyruvate, and amino acids
3. Abnormal glucagon response - no sign. increase in blood glucose
4. Liver stores fat, not carbs - Turns lactate, pyruvate into fatty acids instead of glucose

Question 6

What are the four reactions unique to gluconeogenesis?

Answer 6

1. 2 Pyruvate to 2 Oxaloacetate via Pyruvate Carboxylase
2. 2 Oxaloacetate to 2 PEP via PEP carboxykinase
3. Fructose 1,6-bisphosphate to Fructose 6-phophate/Glucose 6-phosphate via Fructose 1,6 bisphosphatase
4. Glucose 6-phosphate to glucose via glucose 6-phosphatase

Question 7

Is gluconeogenesis the reverse of glycolysis?

Answer 7

Not quite because need to bypass irreversible steps from glycolysis

Question 8

What does Glucose 6-phosphatase produce for release from the cell?

Answer 8

Free glucose!

Question 9

How much energy to make glucose from pyruvate?

Answer 9

6 ATP/GTP

Question 10

What is the main regulated step in gluconeogenesis?

Answer 10

Fructose 1,6-bisphosphatase which forms glucose 6-phosphate from fructose 1,6-bisphosphate

*Responds to Fructose 2,6-bisphosphate

Question 11

What inhibits and stimulates pyruvate carboxylase?

Answer 11

Inhibited by - Insulin

Stimulated by - Acetyl-CoA

Question 12

What inhibits and stimulates PEP carboxykinase?

Answer 12

Inhibited by - Insulin, AMP

Stimulated by - Glucagon

Question 13

What inhibits and stimulates fructose 1,6 bisphosphatase?

Answer 13

Inhibited by - Insulin via Fructose 2,6 bisphosphate, AMP

Stimulated by - Citrate

Question 14

What inhibits and stimulates Glucose 6-Phosphatase?

Answer 14

Inhibited by - Insulin

Stimulated by - Glucagon

Question 15

What is an alternate pathway for the degradation of glucose?

Answer 15

Pentose Phosphate Pathway or Hexose Monophosphate Shunt

Question 16

What does the pentose phosphate Pathway provide?

Answer 16

NADPH for anabolic reactions, defense against reactive oxygen, p450 enzymes

Ribose for nucleotide synthesis

Question 17

What is the pentose pathway important for red blood cells?

Answer 17

Only source of NADPH

Question 18

How does the pentose phosphate pathway meet the needs of the cell?

Answer 18

Exchanges metabolites with gluconeogenesis and glycolysis.

Do so by producing fructose 6 phopshate and glyceraldehyde 3 phosphate in teh nonoxidative phase which enter glycolysis or gluconeogenesis.

Question 19

What does a patient with a Pentose Phosphate Pathway Disorder present with?

Answer 19

Hemolytic anemia - red blood cells lack NADPH for protection against radical stress, bite cells in peripheral blood smear

Jaundice - degradation of heme released from red blood cells

Enlarged spleen - Removal of damaged RBCs from circulation

Question 20

What is the regulated/committed step of Pentose Phosphate pathway?

Answer 20

Glucose 6 phosphate dehydrogenase converting Glucose 6-phosphate to 6-phosphogluconolactone

Question 21

What two reactions in the pentose phosphate pathway produce NADPH, CO2, and ribulose 5P? What reactions are these?

Answer 21

Oxidation reactions

Glucose 6 phosphate dehydrogenase produced 1NADPH

6-phosphogluconate dehydrogenase produces NADPH, CO2, and ribulose 5-phosphate

Question 22

What inhibits glucose 6 phosphate dehydrogenase?

Answer 22

NADPH

Question 23

What occurs in the nonoxidative phase of pentose phosphate pathway?

Answer 23

Converts pentoses to fructose 6 phosphate and glyceraldehyde 3 phosphate

Question 24

Glucose 6 phosphate dehydrogenase deficiency

Answer 24

PPP disorder

Prevalent in Mediterranean and African Americans.

X-linked - affects predominantly males

Depletes RBS of NADPH which lowers radical stress resistance and then radical stress (H2O2) causes hemolytic anemia

Question 25

Describe activities of glycolysis and PPP in a fat tissue that is in fed state

Answer 25

Adipose tissue will want to convert glucose to fatty acids

High insulin, Glycolysis active

Glucose GP oxidized by Glucose 6P dehydrogenase in PPP

Needs NADPH and pyruvate so takes Pentoses not being used from PPP and turns them into F6P and GA3P so they can enter glycolysis

Question 26

Describe activities of glycolysis and PPP in a rapidly dividing cell

Answer 26

High conc of unused NADPH inhibits Glucose 6P dehydrogenase and prevents production of pentose P in PPP

Lack of pentose P directs flow through non-oxidative path of PPP towards production of pentose P from G6P and GA3P

Rapidly diving cells use glycolysis and nonoxidative PPP