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Overview of Gluconeogenesis
Gluconeogenesis generally occurs in cells such as liver and kidney cells because they are responsible for regulating the blood glucose levels in the body. Gluconeogenesis begins in the mitochondrial matrix, where the pyruvate molecules are transformed into oxaloacetate intermediates via the action of pyruvate carboxylase. The oxaloacetate is then reduced into malate for transport across the membranes of the mitochondrion. Once inside the cytoplasm, the malate is oxidized back into oxaloacetate by the action of malate dehydrogenase. Oxaloacetate then undergoes the second step in which phosphoenolpyruvate carboxykinase transforms it into phosphoenolpyruvate (PEP). PEP is then transformed in a series of steps that are reverse of glycolysis until fructose 1,6-bisphosphate is formed. Fructose 1,6-bisphosphate is then transformed into fructose 6-phosphate via an exergonic hydrolysis reaction by the action of fructose 1,6-bisphosphatase. Once glucose 6-phosphate is formed, the fate of this molecule depends on the type of cell we are in. If we are in a liver or kidney cell, the glucose 6-phosphate is transformed into glucose within the lumen of the endoplasmic reticulum. The ER membrane contains a special enzyme called glucose 6-phosphatase that can catalyze the hydrolysis of the ester bond and release the glucose and inorganic phosphate. The glucose and orthophosphate are then moved back into the cytoplasm through two different types of membrane transporters (T2 for inorganic phosphate and T3 for glucose). The dephosphorylated glucose can now exit the cell and enter the blood. If we are not in the liver or kidneys, the glucose 6-phosphate generally is not converted into glucose. Glycerol molecules can enter this pathway as DHAP molecules while amino acids can enter as either pyruvate molecules or oxaloacetate molecules. Lactate enters the cycle as pyruvate.
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