gluconeogenesis
The synthesis of glucose from non-carbohydrate precursors.
Where does gluconeogenesis mainly occur?
Liver (major site) and kidney (minor site).
When is gluconeogenesis most important?
During fasting, starvation, and when liver glycogen is depleted (after ~10–18 hours).
Name the major substrates for gluconeogenesis.
Lactate, glycerol, glucogenic amino acids, propionate (odd-chain fatty acids).
How does lactate enter gluconeogenesis?
Lactate → pyruvate (via LDH).
How does glycerol enter gluconeogenesis?
Glycerol → glycerol-3-P → DHAP.
Which amino acids are used in gluconeogenesis?
Glucogenic amino acids (e.g., alanine).
Why can odd-chain fatty acids contribute to glucose synthesis?
They produce propionyl-CoA → succinyl-CoA → gluconeogenesis.
Which glycolytic enzymes are irreversible and must be bypassed?
Hexokinase/glucokinase, PFK-1, pyruvate kinase.
Which enzymes bypass pyruvate kinase?
Pyruvate carboxylase and PEP carboxykinase (PEPCK).
Where is pyruvate carboxylase located?
Mitochondria.
What cofactor does pyruvate carboxylase require?
Biotin.
What activates pyruvate carboxylase?
Acetyl-CoA.
Why is oxaloacetate converted to malate?
To cross the mitochondrial membrane and generate cytosolic NADH.
Which enzyme bypasses PFK-1?
Fructose-1,6-bisphosphatase.
What molecule inhibits fructose-1,6-bisphosphatase?
Fructose-2,6-bisphosphate.
Which enzyme converts glucose-6-P to glucose?
Glucose-6-phosphatase.
Where is glucose-6-phosphatase found?
Liver and kidney (ER membrane).
How many ATP equivalents does gluconeogenesis use?
6 high-energy phosphates.
Why must glycolysis and gluconeogenesis not occur together?
It would create a futile cycle wasting 4 ATP per turn.
What is the Cori cycle?
Lactate from muscle → liver → converted to glucose → returned to muscle.
What is the role of the Cori cycle?
Maintains blood glucose and removes lactate from muscle.
Why does the Cori cycle cause energy loss?
Liver uses ATP to convert lactate into glucose.
What does the glucose-alanine cycle transport?
Nitrogen and carbon from muscle to liver as alanine.