Lecture 19 - Gluconeogenesis

Question 1

What is Gluconeogenesis?

Answer 1

Synthesis of glucose from non-carb precursors
Maintains blood glucose
- in starvation
- during prolonged exercise
- normal homeostasis
Source of glucose for other biomolecules e.g. polysaccharides
Generates 160g glucose/day for whole body
12g is for brain

Question 2

Gluconeogenesis Pathway

Answer 2

Converts pyruvate into glucose 
Main precursors are:
- lactate
- amino acids
- glycerol
Occurs predominantly in liver and kidney cortex

Question 3

Gluconeogenesis Enzymes

Answer 3

1. Pyruvate carboxylase
2. Phosphoenolpyruvate carboxykinase (PEPCK)
3. Fructose 1,6 bisphosphatase
4. Glucose 6 phosphatase
   Insulin represses all 4 enzymes
   Glucagon and glucocorticoids induce all 4 enzymes

Question 4

Steps for Gluconeogenesis

Answer 4

1. Pyruvate becomes oxaloacetate with help of pyruvate carboxylase
2. Oxaloacetate then becomes phosphoenolpyruvate with help from PEPCK
3. Phosphoenolpyruvate becomes fructose 1,6 bisphosphate
4. This then uses frucotse 1,6 bisphosphatase to convert to fructose 6 phosphate
5. This then converted to glucose 6 phosphate
6. Glucose 6 phosphate then converted to glucose with help from glucose 6 phosphatase

Question 5

Gluconeogenesis links to the TCA Cycle

Answer 5

Pyruvate carboxylase is activated by high Acetyl CoA levels

GTP needed for PEPCK reaction - GTP comes from TCA reaction of succinyl CoA to Succinate reaction

Question 6

Gluconeogenesis Precursors

Answer 6

Alanine
- source of pyruvate
- from muscle
- amino acids classified as glucogenic
Glycerol 
- source of triose phosphate
- from adipose tissue
Lactate
- source of pyruvate
- muscle
- erythrocytes
All sources processed through:
Liver - 80-90%
Kidney 10-20%

Question 7

Cori Cycle

Answer 7

Between glucose and lactate

Occurs between liver cells and cell without mitochondria or when O2 is not available

Question 8

Alanine Cycle

Answer 8

Between glucose and alanine
Occurs between liver cells and cells with mitochondria and when O2 is available
Urea produced

Question 9

Regulation of Gluconeogenesis

Answer 9

More glucagon = more gluconeogenesis

More insulin = inhibits gluconeogenesis

Question 10

Glucose-Alanine Cycle in Fasted State

Answer 10

Muscle will transaminate pyruvate to alanine rather than put it through TCA cycle
Allows it to travel to liver where it can be converted back to pyruvate as muscles cant do gluconeogenesis
Way to use glycogen stores in muscles to help maintain blood glucose