Gluconeogenesis

•  Anaplerosis: Replenishing intermediates that have been used for biosynthesis
• The ATP invested during glycolysis is not returned during gluconeogenesis
• G6Pase only occurs in the liver
• G6Pase System

  • In the liver ER, G6Pase removes the phosphate from G6P to form glucose
  • Glucose diffuses out of the cell via GLUT2 transporters
• Diagnostics with hexokinase:

  1. Deoxyglucose is tagged with fluorine and hexokinase traps it within cells via phosphorylation
  2. The missing -OH group prevents it from being metabolised further, so it can be seen in cells consuming a lot of glucose.
• ATP and citrate inhibit PFK-1
• ADP and AMP stimulate PFK-1
• AMP inhibits FBPase-1
• PFK-2 converts fructose 6-phosphate to fructose 2,6-bisphosphate
• fructose 2,6-bisphosphate is a regulatory molecule made in small amounts
• fructose 2,6-bisphosphate highly activates glycolysis and inhibits gluconeogenesis
• PFK-2 (makes regulatory molecule) and FBPase-2 (breaks down regulatory molecule) are the same enzyme
• The interconversion of PFK-2 and FBPase-2 is catalysed by protein kinase A (PKA)
• PKA is sensitive to cAMP (and therefore glucagon and insulin)
• Reversing the Conversion of PEP to Pyruvate requires two ATP consuming steps
• Pyruvate carboxylase is stimulated by acetyl CoA (produced by fatty acid oxidation)
• PC uses an ATP to add carbon dioxide (obtained from bicarbonate) to pyruvate, forming oxaloacetate
• Where does PC occur?

  Mitochondria
• PEPCK is stimulated by increased transcription/translation of the gene
• PEPCK uses a GTP to decarboxylate oxaloacetate and add a phosphate