Gluconeogenesis & Oxidative Phosphorylation Flashcards Preview

DEMS: Unit II > Gluconeogenesis & Oxidative Phosphorylation > Flashcards

Flashcards in Gluconeogenesis & Oxidative Phosphorylation Deck (16):
1

Metabolic role of gluconeogenesis

  • liver is the most important site for gluconeogenesis
  • kidney has the capability for gluconeogenesis and is responsible for roughly 20% of whole body glucose production under conditions of prolonged starvation.

2

General process of gluconeogenesis

  • Gluconeogenesis is the process whereby glucose is synthesized from non-carbohydrate precursors
  • takes place mostly in the cell cytosol, although pyruvate carboxylase, one of its enzymes, is in mitochondria.

3

Major gluconeogenic precursors & generation

  • lactate
    • formed @ skeletal m. during exercise
    • formed @ RBCs (no mitochondria)
    • lactate ==> pyruvate ==> gluconeogen
  • amino acids
    • alanine, when trans-aminated ==> pyruvate ==> gluconeogen
    • glutamine, when trans-aminated ==> alpha-ketoglutarate ==> gluconeogen
    • AA ==> TCA cycle ==> ocaloacetate ==> gluconeogen
  • glycerol
    • hydrolysis of triglycerides ==> glycerol ==> gluconeogen

4

Can fatty acids be converted to glucose?

  • NO -- no in mammals, anyway
  • FA ==> TCA cycle as acetyl CoA ==> CO2 + electron carriers; leaves no net carbons to contribute to glucose synthesis
  • fatty acids DO provide energy for gluconeogenesis
    • FA oxidation is critical as it generates the ATP necessary for gluconeogenesis which is an energy requiring pathway

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5

General proces of gluconeogenesis

  • gluconeogenesis = ~ reverse of glycolysis
  • EXCEPT certain steps must be bypassed:
    • a. Pyruvate kinase/PEPCK (PEP + ADP ==> pyruvate + ATP)

    • b. Phosphofructokinase (F6P + ATP ==> F1,6BP)

    • c. Hexokinase (Gluc + ATP ==> G6P)

6

Gluconeogenesis bypass rxn #1

  • overall: pyruvate ==> oxaloacetate ==> phosphoenol pyruvate 
  1. pyruvate ==> mitochondria
  2. pyruvate + HCO3- + ATP ==> oxoaloacetate (OAA) + ADP + Pi
    1. ​mediated by Pyruvate carboxylase
    2. pyruvate caroxylase = regulated enzyme
      1. acetyl CoA = positive effector
  3. OAA + NADH + H+ ==> malate + NAD+ 
    1. mediated by malate dehydrogenase (mitochondrial)
  4. malate ==> cytosol ==> OAA
  5. OAA + GTP <==> phosphenolpyruvate + CO2 + GDP
    1. phosphenol pyruvate carboxykinase (PEPCK; cytosol)

7

Pathway and rxn involving pyruvate carboxylase?

  • pathway: gluconeogenesis
  • rxn: pyruvate + HCO3- + ATP ==> oxoaloacetate (OAA) + ADP + Pi
  • regulation
    • acetyl CoA = positive effector

 

8

Pathway and rxn involving malate dehydrogenase (mitochondrial)?

  • pathway: gluconeogenesis OR TCA cycle
  • rxn: OAA + NADH + H+ ==> malate + NAD+ ​

 

9

Pathway and rxn involving PEPCK (cytosol)

  • PEPCK = phosphoenol pyruvate carboxykinase
  • pathway: gluconeogenesis
  • rxn: OAA + GTP <==> phosphenolpyruvate + CO2 + GDP

10

Gluconeogenesis bypass rxn #2

  • fructose-1,6-bisphosphate + H2O ==> F6P + Pi
  • catalyzed by fructose 1,6 bisphosphatase
    • key regulator = fructose 2,6 bisphosphate
    • also regulated by phosphorylation

11

regulation of PFK vs. F-1,6-bisphosphatase (schematic)

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12

Gluconeogenesis bypass rxn #3

  • G6P + H2O ==> glucose + Pi
  • mediated by Glucose-6-phosphatase
    • found in ER membrane @ hepatocytes, kidney cells
  1. G6P ==> ER lumen ==> glucose ==> transported out

13

Mechanisms for generation of energy via oxidative phosphorylation

  • 4 multi protein complexes establish a proton gradient across the inner mitochondrial membrane
  •  [H+] is higher in the intermembrane space. H+ then drives ATP synthase/Complex V to create ATP from ADP.
  • Complex II is not shown in the picture below, but it has the same function as complex I except it oxidizes FADH2.

 

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14

Components of electron transport chain + locations

  • Complex I - IV are embedded in the inner membrane and develop the H+ gradient in the intermembrane space.
    • Complex I uses NADH
    • Complex II uses FADH2
    • Complex III + IV use Fe2+along with CoQ and Cytochrome C respectively
  • ATP synthase, otherwise known as Complex V, is also embedded in the inner membrane

15

Substrates for oxidative phosphorylation

  • FADH2
  • NADH
  • H+
  • O2
  • ADP, Pi
  • electrons!

16

Consequences of defects in electron transport chain

  • inborn defects ==> problems after exercise e.g.:
    • retinal dysfunction
    • encephalopathy
    • Muscle myopathies
  • possible connections to obesity and type 2 diabetes
  • also...
    • heart failure, alzheimer’s, hypoglycemia