Gluconeogenesis (lec 11)

Gluconeogensis

• the creation of 6 carbon glucose from 3-4 carbon precursors, normally non carbohydrate sources

• pretty much the reverse of glycolysis but has 4 extra steps, starts from pyruvate and goes back up

• requires 6 energy equivalents to produce 1 molecule of glucose from 2 pyruvate

precursors for gluconeogenesis

• Lactate: skeletal muscle, erythrocytes

• Amino Acids: dietary protein, muscle protein breakdown

• propionate: derived from fatty acids, amino acids

• glycerol, and stored fats under starvation conditions

The Cori cycle

Purpose: turn lactate to glucose then transport it back to muscles

• After exercise

• Lactate is transported from muscle to liver

• Glucose is transported from liver to muscles

Anabolic Glucose Metabolism

• glucose is made within most organism

• pathway is also known as gluconeogenesis

• process is strikingly similar to glycolysis, with the exception of 4 reactions

Step 1

• pyruvate cannot be directly converted to PEP

• pyruvate carboxylase is in the mitochondria and turned into oxaloacetate (OAA)

• OAA cannot cross mitochondrial membrane so it is converted to malate

• malate is transported to cytosol then converted back to OAA

Step 2

• cytosolic OAA is converted to PEP by PEP carboxykinase (PEPCK)

• Uses GTP— another energy currency

Step 3: Fructose Bisphosphatase

• comes after step 8 of glycolysis

• removes one of the phosphates on F-1,6-bP

• removes 1 x Pi

Step 4: Glucose 6-phospatase

• removes the last Pi

• Allows glucose to leave the cell

A futile cycle

pathways running in opposite directions resulting in a net loss of energy

• this is how we keep cells from spending all the energy they make from glycolysis going gluconeogenesis

An enzyme used in both glycolysis and gluconeogenesis is:

3-phosphoglycerate kinase

Which substrate CANNOT contribute to net gluconeogenesis in mammalian liver?

palmitate