WEEK 2 (Gluconeogenesis)

Question 1

What is Gluconeogenesis?

Answer 1

Metabolic pathway that results in the generation of glucose from amino acids, lactate and glycerol

Question 2

Where does Gluconeogenesis occur during overnight fast?

Answer 2

90% occurs in the liver cells and 10% occurs in the epithelial cells of kidney & intestine

Question 3

Why does the formation of glucose not occur by a simple reversal of glycolysis?

Answer 3

Overall equilibrium of glycolysis strongly favours pyruvate formation

Question 4

What are the pathways from Glycerol, Lactate & Glucogenic amino acids to Glucose?

Answer 4

GLYCEROL - Fatty acids are removed from TRIACYGLYCEROL -> Dihydroxyacetone Phosphate -> Glucogenesis -> GLUCOSE

LACTATE - LACTATE -> PYRUVATE -> OXALACETATE -> Glucogenesis -> GLUCOSE

GLUCOGENIC AMINO ACIDS - INTERMEDIATE OF CITRIC ACID CYCLE -> OXALACETATE -> Glucogenesis -> GLUCOSE

Question 4

What are the pathways from Glycerol, Lactate & Glucogenic amino acids to Glucose?

Answer 4

GLYCEROL - Fatty acids are removed from TRIACYGLYCEROL -> Glucogenesis -> GLUCOSE

LACTATE - LACTATE -> PYRUVATE -> OXALACETATE -> Glucogenesis -> GLUCOSE

GLUCOGENIC AMINO ACIDS - INTERMEDIATE OF CITRIC ACID CYCLE -> OXALACETATE -> Glucogenesis -> GLUCOSE

Question 5

Which Amino acids are Ketogenic?

Answer 5

Leucine & Lysine

Question 6

Which Amino acids are Ketogenic & Glucogenic?

Answer 6

• Phenylalanine
• Tyrosine
• Tryptophan
• Isoleucine
• Threonine

Question 7

Which enzyme is required to convert Pyruvate to Oxaloacetate?

Answer 7

Pyruvate Carboxylase

Question 8

What are the properties of Pyruvate Carboxylase?

Answer 8

• Mitochondrial enzyme
• Requires BIOTIN
• Activated by acetyl-CoA (from B-oxidation)
• Produces OXALOACETATE which cannot leave the mitochondria but is reduced to MALATE that can leave via the MALATE SHUTTLE

Question 9

What is Biotin and which enzymes require it?

Answer 9

Biotin is a Co-factor for carboxylation enzymes

• Pyruvate carboxylase
• Acetyl-CoA carboxylase
• Propionyl-CoA carboxylase
  [All add 1-carbon group via CO2]

Question 10

Describe Biotin deficiency

Answer 10

• Very rare
• Caused by massive consumption of raw egg whites (AVIDIN is found in eggs which binds to Biotin preventing absorption)
• SYMPTOMS: Dermatitis, Glossitis, Loss of appetite, Nausea

Question 11

Which enzyme converts Oxaloacetate (OAA) to Phosphoenolpyruvate?

Answer 11

Phosphoenolpyruvate Carboxykinase

Question 12

What are the properties of Phosphoenolpyruvate Carboxykinase (PEPCK)?

Answer 12

• Cytoplasmic enzyme
• Induced by GLUCAGON and CORTISOL
• OAA is decarboxylated and phosphorylated to PEP in the cytosol by PEPCK
• Requires GTP

Question 13

Which enzyme converts Fructose 1,6-biphosphate to Fructose 6-phosphate?

Answer 13

Fructose- 1,6-biphosphatase

Question 14

What are the properties of Fructose- 1,6-biphosphatase?

Answer 14

• Cytoplasmic enzyme
• Key control point of Gluconeogensis
• Hydrolyses phosphate from fructose-1,6-biphosphate rather than using it to generate ATP from ADP

Question 15

What is needed to convert Fructose-1,6-biphosphate to Fructose-6-phosphate?

Answer 15

• Fructose bisphosphatase
• Glucagon
• Citrate

Question 16

Which enzyme converts Glucose 6-phosphate to D-Glucose?

Answer 16

Glucose 6-phosphatase

Question 17

What are the properties of Glucose-6-phosphatase?

Answer 17

• Found in the lumen of the ENDOPLASMIC RETICULUM
• Found only in the LIVER
• Glucose 6-phosphate is transported into the ER and free glucose is transported back into the cytoplasm where it leaves the cell

Question 18

What regulates the blood glucose level and how does it do this?

Answer 18

Fructose 2,6-biphosphate

When blood glucose level is low, glucagon is released which activates cAMP-DEPENDENT PROTEIN KINASE -> increases F26BP -> Stimulates glycolysis -> Inhibits gluconeogenesis

When blood glucose level is high, insulin is released which which activates PHOSPHOPROTEIN PHOSPHATASE -> decreases F26BP -> Inhibits glycolysis -> Stimulates gluconeogenesis

Question 19

Describe the Cori cycle

Answer 19

During fasting, LACTATE from red blood cells/exercising skeletal muscle is converted in the LIVER to GLUCOSE that can be returned to the red blood cell or muscle

Question 20

Describe the Alanine cycle

Answer 20

Muscle releases alanine which delivers both a GLUCONEOGENIC SUBSTRATE (PYRUVATE) and an AMINO GROUP for urea synthesis. It shuttles amino groups from the muscle to the liver.

Question 21

What happens in the Alanine/Cahill cycle?

Answer 21

1) In the muscle, amino groups are produced from the breakdown of amino acids
2) a-ketoglutarate accepts the amino groups and is converted into glutamate
3) GLUTAMATE transfers the amino group to PYRUVATE producing ALANINE in a reaction catalysed by ALANINE TRANSAMINASE
4) At the liver, alanine is taken up and converted into pyruvate which is used for GLUCONEOGENESIS (making glucose)
5) Glucose is exported to the bloodstream and some back into the muscle

Question 22

What is the link between Alcoholism and Hypoglycemia?

Answer 22

Alcoholics are very susceptible to hypoglycaemia since
- Poor nutrition
- Alcohol metabolised to acetate
- High amounts of cytoplasmic NADH formed by alcohol dehydrogenase and acetaldehyde dehydrogenase

interfere with GLUCONEOGENESIS

Question 23

How does high NADH interfere with Gluconeogenesis?

Answer 23

High NADH favours the formation of:
- Lactate from pyruvate
- Malate from OAA in the cytoplasm
- Glycerol 3-phosphate from DHAP

This diverts important gluconeogenic substrates from entering the pathway