Gluconeogenesis

• synthesis of glucose

• maintains blood glucose - tissues required(blood,testes) , starvation, prolonged exercise, normal homeostasis

• source of glucose - polysaccharides, glycolipids, glycoproteins

• generates 160g/day - body

• 120g/day - brain

Gluconeogenesis

• converts pyruvate to glucose

• occurs in liver and kidneys

• irreversible to glycolysis (but no completely)

Pathway of Gluconeogenesis

• Pyruvate carboxylase

• PEPCK

• Fructose 1,6 1,6-bisphosphatase

• glucose 6 phosphatase

• Insulin represses these enzymes

• Glucagon/glucocorticoids induce all of these enzymes

Enzymes

1. pyruvate to oxaloacetate - via pyruvate carboxylase

2. oxaloacetate to phosphoenolpyruvate - via phosphoenolpyruvate carboxykinase

3. phosphatase - reverse of glycolysis 1st/2nd steps

steps

• regulates gluconeogenesis: i

• If GTP is used up, the TCA cycle does not cycle properly, as gluconeogenesis is removing oxaloacetate from the cycle if it is not supplied directly from pyruvate.

• If the cycle stops, so does GTP synthesis, and the PEPCK-catalysed reaction cannot occur.

• GTP - comes from TCA reaction

GTP from TCA

• alanine/ other gluogenic amino acids - source of pyruvate from muscle

• glycerol - source of triose phosphate - adipose tissue

• lactate - source of pyruvate, muscle and erythrocytes

• 80% - liver, 20% kidneys

Prescursors - what can be used to make glucose

• glucose to lactate

• between liver cells and cells without mitochondria, anaerobic

Coric cycle

• requires 6 ATP to turn into a favourable reaction

ATP

• glucose to alaine

• aerobic

• liver cells and cells with mitochondria

• urea produced

• glucose - 2 pyruvates - 2 alanine

• muscle trans-aminate pyruvate to alainine rather than TCA

Alanine cycle

• Acetyl CoA levels in liver mitochondria - control pyruvate carboxylase

• high aceytl coA - turn on enzymes

• low aceytl coA - turn off the enzyme

• Phosphofructokinase-2- fructose 1,6, biphosphatase complex - regulates the process

Regulation

• almost the reverse of glycolysis

• uses 6 ATP

key points for gluconeogenesis