Gluconeogenesis is the
synthesis of glucose from non-carb precursors
What are the precursors for gluconeogenesis?
1) Lactate (from skeletal muscle via lactic acid fermentation)
2) Amino acids (from proteins in diet vs starvation = breakdown of proteins in skeletal muscle)
3) Glycerol from triacylglycerols hydrolysis (may enter gluconeogenic or glucolytic pathway at DHAP)
Pyruvate to phosphoenolpyruvate
Pyruvate + ATP + CO2 +H2O -> oxaloacetate +ADP + Pi + H+
enzyme: pyruvate carboxylase
Oxaloacetate +GTP -> phosphoenolpyruvate + GDP + CO2
enzyme: phosphoenolpyruvate carboxykinase
Pyruvate to oxaloacetate requires:
Biotin (vit B7) - carrier of activated CO2, occurs in the mitochondria
Need to get oxaloacetate from mitochondria to cytosol!!
Oxaloactate -> malate (which now passes through membrane to cytosol) -> oxaloacetate now in cytosol!
Gluconeogenesis is the same as glycolysis from _____ to ______
Phosphoenolpyruvate to F-1,6-BP
F-1,6-BP to F-6-P enzyme is:
fructose 1,6-biphosphatase
F-6-P to G-6-P is
like in glycolysis
G-6-P to glucose enzyme:
glucose 6-phosphatase
In most tissues, gluconeogenesis ends with the formation of g-6-p because
there is a lack of glucose-6-phophatase, so instead make glycogen
Gluconeogenesis and glycolysis regulation for f-6-p < > f-1,6-bp
1) energy is needed = high AMP
- glycolysis/PFK is activated by AMP and F-2,6-BP
- PFK is inhibited by citrate, H+, and ATP
2) Energy is high = high ATP and high citrate
- Gluconeogenesis/Fructose 1,6-biphosphatase is activated by citrate
- F-1,6-BP is inhibited by AMP amd F-2,6-BP
In the liver, gluconeogenesis and glycolysis regulation
1) Energy is needed = high ADP
- F-1,6-BP activates pyruvate kinase
- ATP and Alanine inhibit pyruvate kinase
2) Energy is high = high ATP, alanine, and acetyl CoA
- ADP inhibits PEP carboxylase and pruvate carboxylase
- Acetyl CoA actives pyruvate carboxylase