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Flashcards in Gluconeogenesis Deck (19)
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describe purpose of gluconeogenesis

  • provision of glucose for cells that need glucose as metabolic fule (RBC, brain, renal medulla)
  • synthesis of glucose from non-carbohydrates and release into the blood
  • sole provider for blood glucose once glycogen is depleted in the liver


where in the body and when is gluconeogenesis performed?

  • gluconeogenesis occurs in liver (periportal cells) and kidneys
  • gluconeogenesis takes place during fasting or flight and fight situations
    • after an overnight fast gluconeogenesis occurs:
      • 90% in liver and 10% in kidney
    • during prolonged starvation, gluconeogenesis occurs:
      • 60% in liver and 40% in kidney


which cellular compartments are involved in gluconeogenesis?

  • most of the enzymes for gluconeogenesis are in the cytosol
    • the reversible steps are shared with enzymes of glycolysis
  • glucose 6-phosphatase is found in the ER
  • pyruvate carboxylase is found in the mt
  • PEP carboxykinase is found in the mt and in cytosol


gluconeogenesis takes place mainly in _____ and glycolysis mainly in _____

gluconeogenesis takes place mainly in periportal cells and glycolysis mainly in perivenous cells

they do not take place at the same time


the (4) enzymes catalyzing the irreversible steps of gluconeogenesis are:

  1. pyruvate carboxylase
  2. PEP carboxykinase
  3. fructose 1,6 bisphosphatase
  4. glucose 6-phosphatase


what are the substrates for gluconeogenesis?

  • during fasting, the liver obtains via the blood:
    • amino acids from degradation of tissue proteins, especially muscle during fasting. major source for gluconeogenesis
      • ​alanine and glutamine
    • lactate from exercising muscle or from RBC
    • glycerol from degradation of TAGs in fat cells


what is the importance of acetyl CoA in gluconeogenesis?

  • acetyl CoA from B-oxidation is used as allosteric activator for pyruvate carboxylase


describe the glucose-alanine cycle

  • the glucose-alanine cycle describes hepatic gluconeogenesis using alanine released by muscle during fasting
    • the formed glucose is released into the blood and can be taken up by muscle
  • this cycle is costly regarding ATP but is needed to provide blood glucose during fasting independent of muscle exercise


describe the Cori cycle

  • the Cori-cycle describes hepatic gluconeogenesis using the lactate formed by anaerobic glycolysis in muscle and release of glucose for uptake into muscle for glycolysis
  • the release of lactate from RBC or other cells performing anaerobic glycolysis is somtimes included in the Cori cycle


describe enzymes involved in pyruvate formation from the glucose-alanine cycle and the Cori cycle

  • pyruvate is formed from:
    • alanine catalyzed by alanine aminotransferase
    • lactate catalyzed by lactate dehydrogenase


describe the carboxylation of pyruvate

  • pyruvate is transported into mt and is carboxylated to oxaloacetate catalyzed by pyruvate carboxylase
    • the enzyme needs the vitamin biotin as a coenzyme and the allosteric activation by acetyl CoA
  • acetyl CoA is formed during fasting by mt fatty acid degradation and not by pyruvate dehydrogenase which is inhibited


how does pyruvate carboxylase form oxaloacetate?

  • pyruvate carboxylase uses pyruvate, CO2, ATP and forms oxaloacetate
  • pyruvate carboxylase is found in mt and needs acetyl CoA as an absolute allosteric activator otherwise it is not active


describe the PEP carboxykinase rxn

  • oxaloacetate formed in mt cannot pass through the inner mt membrane, therefore it is turned into malate which can travel to the cytosol, combines with NAD+, and is converted back to oxaloacetate 
  • oxaloacetate is now a substrate for cytosolic PEP carboxykinase
  • PEP carboxykinase uses GTP and forms PEP, GDP and CO2
    • this enzyme is induced by cortisol


describe function of fructose 1,6-bisphosphatase

  • fructose 1,6-bisphosphatase is the ultimately short-term regulated enzyme
  • inhibition of F1,6BPase by:
    • AMP at low energy levels (high AMP signals low ATP)
    • fructose 2,6-bisphosphate (formed when insulin is high)


how and when is hepatic frucose 2,6 bisphosphate formed and inhibits gluconeogenesis?

  • it is formed by the bifunctional enzyme when the serum insulin/glucagon ratio is high 
    • this enzyme has a phosphorylation site that responds to hormonal regulation
  • at high blood glucose levels, hepatic glycolysis is favored and gluconeogenesis is inhibited


describe the function of the bifunctional enzyme

  • only one gene and one protein for both irreversible enzyme activities
  • insulin leads to dephosphorylated bifunctional enzyme that forms fructose 2,6-bisP and promotes glycolysis (PFK-2 is active)
  • glucagon leads to the phosphorylated bifunctional enzyme that degrades frucose 2,6-bisP and promotes gluconeogenesis (PFK-2 is inactive)


what are the energy requirements of gluconeogenesis?

  • glucose synthesis from 2 pyruvates needs 4 ATP, 2 GTP and 2 NADH
  • fatty acid degradation in mt provides the energy needed for hepatocytes during gluconeogenesis 


describe location and function of glucose 6-phosphatase

  • glucose 6-phosphatase is an enzyme that is bound in the ER membrane and acts toward the ER lumen
  • glucose 6-phosphate is transported from the cytosol into the ER lumen and is cleaved by glucose 6-phosphatase to free glucose and inorganic phosphate which are transported into cytosol


glucose 6-phosphatase is used in both ____ and _____ 

  • glucose 6-phosphatase is used in both gluconeogenesis and glycogen degradation