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    Gluconeogenesis New

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    Gluconeogenesis New

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    of 10

    Carbohydrate Metabolism

    Gluconeogenesis

    Dr. Mahesh Kumar


    MBBS, DCP, PhD

    Assistant Professor
    Gluconeogenesis
    Gluconeogenesis
    • Gluconeogenesis is the synthesis of new glucose molecules from non
    carbohydrate sources (pyruvate, lactate, glycerol, or fat).
    • This process takes place primarily in the liver during periods of low
    glucose, that is, under conditions of fasting, starvation, and low
    carbohydrate diets.
    • Certain key organs, including the brain, can use only glucose as an energy
    source; therefore, it is essential that the body maintain a minimum blood
    glucose concentration.
    • When the blood glucose concentration falls below that certain point, new
    glucose is synthesized by the liver to raise the blood concentration to
    normal.
    Gluconeogenesis
    Gluconeogenesis
    Gluconeogenesis
    • Gluconeogenesis is not simply the reverse of glycolysis. There are some important
    differences.
    • Pyruvate is a common starting material for gluconeogenesis.
    • First, the pyruvate is converted into oxaloacetate.
    • Oxaloacetate then serves as a substrate for the enzyme phosphoenolpyruvate carboxykinase
    (PEPCK), which transforms oxaloacetate into phosphoenolpyruvate (PEP).
    • From this step, gluconeogenesis is nearly the reverse of glycolysis.
    • Phosphoenolpyruvate (PEP) is converted back into 2-phosphoglycerate, which is converted into 3-
    phosphoglycerate.
    • Then, 3-phosphoglycerate is converted into 1,3 bisphosphoglycerate and then into glyceraldehyde-
    3-phosphate.
    • Two molecules of glyceraldehyde-3-phosphate then combine to form fructose-1-6-bisphosphate,
    which is converted into fructose 6-phosphate and then into glucose-6-phosphate.
    • Finally, a series of reactions generates glucose itself.
    • In gluconeogenesis (as compared to glycolysis), the enzyme hexokinase is replaced by glucose-6-
    phosphatase, and the enzyme phosphofructokinase-1 is replaced by fructose-1,6-bisphosphatase.
    • This helps the cell to regulate glycolysis and gluconeogenesis independently of each other.
    • Overview
    • Definition: a series of metabolic events that allows for the production of glucose from non-
    carbohydrate precursors.
    • Purpose: During fasting, gluconeogenesis becomes the main method of glycemic control after
    glycogen stores are depleted (after 1–3 days of normal activity).
    • Cell location: : Responsible enzymes are located in the cytosol and mitochondria

    • Sites of gluconeogenesis
    • Primarily carried out in the liver
    • Renal cortex
    • Intestinal epithelium
    • Skeletal muscle

    • Rate-limiting enzyme: fructose 1,6-bisphosphatase


    • Non-carbohydrate precursors: Glucogenic amino acids (mainly alanine and glutamine), lipids,
    glycerol, pyruvate, and lactate can all be converted to glucose in order to preserve serum glucose
    levels. These reactions are energy intensive, as they rely on the consumption of high-energy
    molecules (GTP, ATP).
    Figure 7.
    Gluconeogenesis is the synthesis
    of glucose from pyruvate, lactate,
    glycerol, alanine, or glutamate.
    Gluconeogenesis and Glycolysis Pathways

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