Gluconeogenesis Flashcards Preview

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Flashcards in Gluconeogenesis Deck (19)
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1

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

2

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

3

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

4

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

5

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

6

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

7

what is the importance of acetyl CoA in gluconeogenesis?

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

8

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

9

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

10

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

11

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

12

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

13

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

14

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)

15

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

16

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)

17

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 

18

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

19

glucose 6-phosphatase is used in both ____ and _____ 

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