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 PFK1 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 6phosphatase 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