Lecture 14: Gluconeogenesis

Question 1

Cellular energy utilisation:

When won’t a reaction proceed? How can you make them precede?

Answer 1

Regardless of whether there is an enzyme a reaction will not proceed if it is thermodynamically unfavourable.
Cell synthesise large complex molecules eg proteins, DNA etc (these types of synthesis aren’t thermodynamically favourable)
In order to proceed they have to be coupled to another reaction that releases energy.
Within the cell, this type of reaction is coupled to ATP hydrolysis ie ATP to ADP + P

Question 2

Cellular energy utilisation:

What is the energy used to do?

Answer 2

1. Biosynthetic work: eg
   -carbohydrate synthesis, fat synthesis, DNA/RNA synthesis, protein synthesis
2. Transport work:
   Eg Na/K pump
   -generation of membrane potentials
   -nerve conduction
3. Mechanical work:
   Eg muscle contraction
   -activity of flagella and cilia
4. Mechanical work

Question 3

Carbohydrate biosynthesis:

Why do cells need to synthesis carbohydrates?

Answer 3

• reserve materials eg glycogen, starch
• the carbohydrate moiety of glycoproteins and glycolipids (cell membranes)
• components of connective tissue eg hyaluronic acid
• cell wall materials (bacteria and plants)

Question 4

Carbohydrate biosynthesis:
We know that plants synthesis glucose from CO2 via the dark reactions of photosynthesis.
What about heterotrophs such as animals? Ie the synthesis of glucose from non-carbohydrate precursors

Answer 4

Gluconeogenesis:
The major site of this occurs in the liver and kidneys
-other tissues can produce glycogen but not glucose eg skeletal muscle
Glycolysis:
Glucose —> 2 pyruvate
Gluconeogenesis:
2 pyruvate —-> glucose however gluconeogenesis isn’t a reverse of glycolysis. Glycolysis has 3 irreversible steps that must be passes

Question 5

Glycolysis has 3 irreversible steps that must be passes for gluconeogenesis. What are they?

Answer 5

1. Phospheonolpyruvate -> pyruvate
2. Fructose-6-phosphate + ATP ——-> (phosphofructokinase) fructose-1,6-bi phosphate + ADP
3. Glucose -> glucose -6 phosphate
   These three reactions are overcome by four enzymes essential for gluconeogenesis

Question 6

These three reactions are overcome by 4 enzymes known as the gluconeogenic quartet.
Name them and what reactions the overcome

Answer 6

1. Pyruvate carboxylase (mitochondria)
   Pyruvate + CO2 + ATP -> oxaloacetate + ADP + Pi
2. PEP carboxykinase (cytoplasm)
   Oxaloacetate + GTP –> PEP + GDP + CO2
3. Fructose 1,6-diphosphatase (cytoplasm)
   Fructose -1,6-diphosphatase + H2O –> fructose 6-P + Pi
4. Glucose 6-phosphatase (endoplasmic reticulum)
   Glucose 6-P + H2O –> glucose + Pi

Question 7

What is the overall reaction of gluconeogenesis

Answer 7

Pyruvate + ATP + GTP —> phosphoenolpyruvate + ADP + GDP + Pi