Gluconeogenesis

Cards (58)

  • pH is not a metabolic signal in the liver because it does not produce lactic acid
  • The formed Citrate is an inhibitor of phosphofructokinase as the metabolite produced from the substrate is already enough
  • Fructose 2,6 bisphosphate is formed from a deviation in glycolysis
  • Fructose 1,6 bisphosphate stimulates forward to pyruvate by keeping the PK in pace with PFK to prevent any buildup
  • In the liver, high concentration of fructose 6 phosphate activates phosphofructokinase through an intermediary fructose 2, 6 bisphosphate
  • PFK has a tight and relaxed conformation, and ATP is both an inhibitor and a substrate
  • ATP as a substrate favors T and R conformation, while ATP as an inhibitor favors T conformation
  • Fructose 2,6 Bisphosphate is formed by phosphorylating with PFK 2 from Fructose 6 phosphate
  • Fructose 2,6 Bisphosphate releases its phosphate with the enzyme Fructose 2,6 Bisphosphatase to produce Fructose 6 Phosphate
  • Fructose 2,6 Bisphosphate is an allosteric effector which activates PFK 1 to shift conformational equilibrium to the R state
  • In the liver, hexokinase has another isozyme called glucokinase which is not inhibited by glucose 6 phosphate
  • Glucokinase has a high Km value and a low affinity of glucose
  • Glucokinase can phosphorylate glucose if the concentration of glucose in blood is high
  • The low affinity of glucokinase allows brain, muscle and RBC to call glucose, without wasting any energy
  • Pyruvate kinase has The liver and muscle isozymic forms
  • The Liver enzyme behave much like the muscle enzyme
  • In the pyruvate, the L form is controlled by covalent modification through phosphorylation
  • Glucagon is released when the blood glucose is low, activating the phosphatase function of PFK 2 reducing level of F2,6 Bisphoshate in the cell decreasing PFK 1
  • Insulin is released when blood glucose are high. Activates the kinase function of PFK 2, increasing the fructose 2,6 bisphosphate in the cell thereby activating PFK 1
  • Gluconeogenesis is an important pathway during a longer period of starvation
  • The substrates for gluconeogenesis include Lactate, Glycerol, and Alanine
  • Lactate is released by the skeletal muscle from the Cori cycle. Liver lactate It is converted with lactate dehydrogenase requiring NAD+ and becomes pyruvate and NADH
  • Glycerol can be converted to Dihydroxyacetone phosphate which can enter into gluconeogenesis
  • Pyruvate is the deaminated form of Alanine
  • Alanine is generated from pyruvate in exercising muscle, Alanine is converted to pyruvate and then glucose in the liver
  • Oxidation of Glycerol 3 phosphate to form Dihydroxyacetone phosphate occurs when cytoplasm NAD+ concentration is high
  • Large amounts of pyruvate is produced at exercising muscles, with glutamate and the enzyme alanine transaminase, it is converted to alanine and alpha ketoglutarate
  • Noncarbohydrate precursors are converted to Pyruvate or enter glycolysis at a later intermediate of like oxaoacetate or DHAP
  • Aspartic acid and NAD+ when deaminated with Aspartate dehydrogenase becomes oxaloacetate and NADH
  • Glutamate with NAD+ when trans aminated with glutamate dehydrogenase becomes alpha ketoglutarate and NADH
  • Fructose bisphosphatase and Glucose 6 phosphatase releases the energy of inorganic phosphate, an irreversible process
  • Gluconeogenesis in the liver and kidney maintain glucose in the blood so that the brain and muscle can extract sufficient glucose to meet their metabolic demands
  • Lactate, Pyruvate, citric acid cycle intermediate such as oxaloacetate, and carbon skeletons of most amino acids
  • The three high energy compounds or the irreversible reactions in glycolysis are bypassed by gluconeogenesis to be spontaneous
  • The three high energy compounds are Fructose 1,6 Bisphosphate, Glucose 6 Phosphate, and Pyruvate
  • The first step is in the mitochondria, where pyruvate is carboxylated with ATP and carbonic acid with the enzyme pyruvate carboxylase yielding Oxaloacetate, inorganic phosphate and ADP
  • There are 2 generated pyruvate, which needs 2 ATP
  • Oxaloacetate must be migrated to the cytosol for the reaction to proceed
  • In reaction 2, oxaloacetate used guanosine triphosphate (GTP) as a source of phosphate group with the enzyme PEP carboxykinase by decarboxylation and phosphorylation to yield Phosphoenol pyruvate, GDP and CO2
  • The GTP that is used by PEPCK is provided by Succinyl CoA synthetase, an enzyme linked the citric acid cycle