Gluconeogenesis

When does gluconeogenesis occur?

After prolonged starvation

Sources of non-carbohydrate precursors

Lactate, glucogenic amino acids, glycerol

Sources of lactate

Red blood cells and skeletal muscle

The Cori Cycle

Lactate transport to liver via bloodstream → converted to glucose → return to bloodstream

Importance of Cori cycle

Shifts metabolic burden from muscles to liver

Sources of glucogenic amino acids

Muscle protein breakdown

Glucose-alanine cycle

Alanine enters liver → converted to glucose → re-enters bloodstream

Importance of glucose-alanine cycle

Transports amino acids in bloodstream in non-toxic form

Source of glycerol

Triglyceride lipolysis in adipose tissue

Glycerol transport to liver

Glycerol enters liver via bloodstream → glycerol conversion to glycerol 3-phosphate → dihydroxyacetone phosphate

Which steps in gluconeogenesis bypass step 10 in glycolysis?

Step 1 and 2

Step 1

Pyruvate → oxaloacetate

Enzyme used in Step 1

Pyruvate carboxylase

Where does Step 1 occur?

In the mitochondria

Expense of Step 1

1 ATP

Step 2

Oxaloacetate to phosphoenolpyruvate

Enzyme used in Step 2

Phosphoenolpyruvate carboxykinase

Expense of Step 2

1 GTP

Steps 3-8

Reverse of glycolysis

Which step of gluconeogenesis bypasses step 3 in glycolysis?

Step 9

Step 9

Fructose 1,6-biphosphate → fructose 6-phosphate

Enzyme used in step 9

Fructose 1,6-biphosphatase

Step 11

G6P transported in sER, dephosphorylated to glucose

Enzyme used in step 11

Glucose 6-phosphatase

Location of glucose 6-phosphatase

Bound to inner membrane of sER

Energetics to synthesize 1 glucose molecule

4 ATP, 2GTP, 2NADH

Regulatory enzymes of gluconeogenesis

Pyruvate carboxylase, fructose 1,6-biphosphatase, fructose 2,6-biphosphate

Regulatory steps of gluconeogenesis

Step 1 and 9

What activates pyruvate carboxylase?

Acetyl-CoA

What inhibits pyruvate carboxylase?

ADP

What activates Fructose 1,6-biphosphatase?

Citrate

What inhibits Fructose 1,6-biphosphatase?

AMP and fructose 2,6-biphosphate

Hormonal control of Fructose 2,6-biphosphate

Insulin → synthesis
Glucagon → suppression