Phosphorylation & dephosphorylation as a mechanism for metabolic control

High carbon (Energy rich) Low carbon (Energy Poor)

  • Phosphorylation is the most common covalent regulatory mechanism, and occurs of the serine, threonine or tyrosine residues of proteins in the cell.
  • Phosphate groups are added by kinases and removed by phosphatases.

High carbon/energy rich cell:

  • High blood glucose levels = high blood insulin levels.
  • When insulin binds to its receptor it causes the activation of a phosphoprotein phosphatase, which removes phosphate groups from proteins.
  • Gluconeogenesis and glycolysis are partially regulated by phosphorylation and dephosphorylation: in a high energy cell, PFK2 is dephosphorylated which activates the enzyme.
  • PFK2 converts F-6-P to F-2,6-diP which favours glycolysis over gluconeogenesis. This allows the carbon to flow through glycolysis to the TCA cycle.
  • Pyruvate kinase in glycolysis is also regulated by phosphorylation and dephosphorylation.
  • Another pathway that is regulated similarly is the synthesis of glycogen.
  • When there is high energy/carbon, once again insulin is high and leads to activation of a phosphoprotein phosphatase.
  • This PPP removes the phosphate from phosphorylase and phosphorylase kinase, inactivating them and prevents the breakdown of glycogen.
  • It also removes the phosphate from glycogen synthase which activates the enzyme- this leads to the synthesis of glycogen from glucose precursors.

Low energy/ low carbon cells:

  • When glucose (carbon) is low, glucagon levels are high in the blood.
  • Glucagon binding to its receptors leads to the activation of a protein kinase which adds phosphate groups to proteins in the cell.
  • In glycolysis and gluconeogenesis: when glucagon is high, a protein kinase will add a phosphate group to PFK2.
  • This phosphorylation inactivates the enyzyme, decreasing the levels of F-2,6-diP, which usually inhibits gluconeogenesis and stimulates glycolysis.
  • Due to less F-2,6-diP, gluconeogenesis is favoured over glycolysis.
  • Now gluconeogenesis will synthesise glucose which can enter the blood stream to increase the blood sugar levels again.
  • As for glycogen synthesis and breakdown: the kinase activated in the cell adds a phosphate group to phosphorylase kinase activating it and to glycogen synthase inactivating it.
  • Phosphorylase kinase will then phosphorylate phosphorylase which breaks down glycogen stores, making glucose.

 

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