Gluconeogenesis

Major site of gluconeogenesis

liver (also occurs in kidneys)

Step 1

pyruvate is converted to oxaloacetate

What enzyme converts pyruvate to oxaloacetate?

pyruvate carboxylase (ATP is needed and biotin (vitamin B7) is a cofactor)

Step 2

oxaloacetate is converted to phosphoenolpyruvate (PEP)

What enzyme converts oxaloacetate to PEP?

PEP carboxykinase (PEPCK) (GTP is consumed)

Step 3

phosphoenolpyruvate (PEP) to 2-phosphoglycerate (2PG) by enolase

Step 4

2-phosphoglycerate (2PG) to 3-phosphoglycerate (3PG) by phosphoglycerate mutase

Step 5

3-phosphoglycerate (3PG) to 1,3-bisphosphoglycerate (1,3-BPG) by phosphoglycerate kinase 

Step 6

1,3-bisphosphoglycerate (1,3-BPG) to two glyceraldehyde phosphate (GAP/G3P) by glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Step 7

1 glyceraldehyde phosphate (GAP/G3P) to dihydroxyacetone phosphate (DHAP) by triose phosphate isomerase

Step 8

dihydroxyacetone phosphate (DHAP) and glyceraldehyde phosphate (GAP) to fructose-1,6-bisphosphate (FBP) by aldolase

Step 9

fructose-1,6-bisphosphate (FBP) to fructose-6-phosphate (F6P) by fructose bisphosphatase

Step 10

fructose-6-phosphate (F6P) to glucose-6-phosphate (G6P) by phosphoglucose isomerase

Step 11

glucose-6-phosphate (G6P) to glucose by glucose-6-phosphatase

allosteric modulator of glycolysis and gluconeogenesis

fructose-2,6-bisphosphate (F2,6P)

high concentration of fructose-2,6-bisphosphate activates

glycolysis (activates phosphofructokinase)

high concentration of fructose-2,6-bisphosphate inhibits

gluconeogenesis (inhibits fructose bisphosphatase)