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    Gluconeogenesis is the process by which the liver converts precursors like lactate, pyruvate, glycerol and amino acids into glucose. This occurs primarily in the liver during periods of fasting when glucose needs to be synthesized from non-carbohydrate sources. The major precursor is pyruvate, which can come from lactate produced in muscles during exertion. All amino acids except leucine and lysine can contribute to gluconeogenesis. Key regulatory enzymes allow certain steps of glycolysis to be bypassed, generating phosphoenolpyruvate from pyruvate, which is then decarboxylated and phosphorylated to produce glucose-6-phosphate and ultimately glucose through additional steps. The

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    Gluconeogenesis is the process by which the liver converts precursors like lactate, pyruvate, glycerol and amino acids into glucose. This occurs primarily in the liver during periods of fasting when glucose needs to be synthesized from non-carbohydrate sources. The major precursor is pyruvate, which can come from lactate produced in muscles during exertion. All amino acids except leucine and lysine can contribute to gluconeogenesis. Key regulatory enzymes allow certain steps of glycolysis to be bypassed, generating phosphoenolpyruvate from pyruvate, which is then decarboxylated and phosphorylated to produce glucose-6-phosphate and ultimately glucose through additional steps. The

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    23 views16 pages

    Gluco Neo Genesis

    Uploaded by

    waldo_reyes_1
    Gluconeogenesis is the process by which the liver converts precursors like lactate, pyruvate, glycerol and amino acids into glucose. This occurs primarily in the liver during periods of fasting when glucose needs to be synthesized from non-carbohydrate sources. The major precursor is pyruvate, which can come from lactate produced in muscles during exertion. All amino acids except leucine and lysine can contribute to gluconeogenesis. Key regulatory enzymes allow certain steps of glycolysis to be bypassed, generating phosphoenolpyruvate from pyruvate, which is then decarboxylated and phosphorylated to produce glucose-6-phosphate and ultimately glucose through additional steps. The

    Copyright:

    Attribution Non-Commercial (BY-NC)
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    of 16

    Gluconeogenesis

    Ronwaldo Reyes

    Gluconeogenesis
    A process whereby precursors such as lactate, pyruvate, glycerol, and amino acids are converted to glucose. Occurs in the Liver Fasting requires all the glucose to be synthesized from these non-carbohydrate precursors. Major precursor for glucose is Pyruvate

    Sources of Pyruvate
    Lactate mostly from muscle. Lactate is produced in great quantities during exertion. Lactate is released from the muscles to the blood and travels to the liver for conversion to pyruvate and, ultimately to glucose.

    All Amino Acids can feed into gluconeogenesis except leucine and lysine

    Irreversible glycolytic steps bypassed


    Glycolysis
    1. 2. 3. Hexokinase (hexK) Phosphofructokinase-1 (PFK-1) Pyruvate kinase (PyrK)

    Gluconeogenesis
    by Glucose-6-phosphatase by Fructose 1,6-bisphosphatase (FBP-1)

    by Pyruvate Carboxylase & Phosphoenolpyruvate carboxykinase (PEPCK)

    These 3 key enzymes

    Pyruvate can go up or down depending upon energy needs

    First bypass step is generation of PEP from pyruvate via oxaloacetate

    Addition of CO2 to pyruvate to form oxaloacetate

    Hydrolysis of ATP

    Decarboxylation and phosphorylation to PEP


    Regulation of FBP-1 by AMP and F2,6P

    2nd & 3rd bypass steps are near the end of gluconeogenesis (top of glycolysis)
    Regulation of FBP-1 by AMP and F2,6P

    Dephosphorylation of G6P, 3rd bypass reaction

    Glucose 6-phosphatase removes the phosphate to liberate free glucose

    G6Pase glucose-6-P + H2O glucose + Pi


    This is primarily a function of the liver to buffer blood glucose levels G6Pase is NOT present in brain and muscle! tissues) (Gluconeogenesis does not occur in these

    Gluconeogenesis is energetically expensive to cells (hepatocytes)

    cost

    Liver is the major source of blood glucose from GN


    Is the primary gluconeogenic organ Produces glucose for export to brain, muscle, RBCs Uses many small metabolites and fatty acids to feed GN Liver function is highly sensitive to insulin & glucagon

    The Cori Cycle


    Gluconeogenesis

    6 ATP 2

    Lactate and glucose shuttle between active muscle/RBC and liver (glucagon/insulin reg.) Liver gluconeogenesis buffers the blood glucose for use by muscle, RBCs and brain (120 g/day) *Note: the brain fully oxidizes glucose, so it does not funnel back lactate

    RBCs
    2 ATP Glycolysis

    THANK YOU

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