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    1 Gluconeogenesis

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    emery
    1. The document discusses gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate carbon sources in the liver and kidneys. 2. Key pathways involved include the Cori cycle, which involves the interconversion of lactate and glucose between tissues but does not lead to net glucose production, and the alanine cycle. 3. Gluconeogenesis is regulated by hormones like glucagon and insulin, as well as by enzymes involved in glycolysis and gluconeogenesis that are activated or inhibited under different conditions like fasting.

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    1 Gluconeogenesis

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    emery
    58 views31 pages
    1. The document discusses gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate carbon sources in the liver and kidneys. 2. Key pathways involved include the Cori cycle, which involves the interconversion of lactate and glucose between tissues but does not lead to net glucose production, and the alanine cycle. 3. Gluconeogenesis is regulated by hormones like glucagon and insulin, as well as by enzymes involved in glycolysis and gluconeogenesis that are activated or inhibited under different conditions like fasting.

    Original Description:

    Lecture about gluconeogenesis metabolic pathway

    Original Title

    1-Gluconeogenesis

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    1. The document discusses gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate carbon sources in the liver and kidneys. 2. Key pathways involved include the Cori cycle, which involves the interconversion of lactate and glucose between tissues but does not lead to net glucose production, and the alanine cycle. 3. Gluconeogenesis is regulated by hormones like glucagon and insulin, as well as by enzymes involved in glycolysis and gluconeogenesis that are activated or inhibited under different conditions like fasting.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    58 views31 pages

    1 Gluconeogenesis

    Uploaded by

    emery
    1. The document discusses gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate carbon sources in the liver and kidneys. 2. Key pathways involved include the Cori cycle, which involves the interconversion of lactate and glucose between tissues but does not lead to net glucose production, and the alanine cycle. 3. Gluconeogenesis is regulated by hormones like glucagon and insulin, as well as by enzymes involved in glycolysis and gluconeogenesis that are activated or inhibited under different conditions like fasting.

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    GLUCONEOGENESIS

    Peter J. Roach
    MS 405A
    274-1582
    proach@iupui.edu
    B800
    Fall 2014
    GLUCONEOGENESIS
    Objectives:
    1. Identify the carbon sources suitable for glucose
    synthesis via gluconeogenesis. Identify the most
    important organs that carry out gluconeogenesis.

    2. Diagram the pathway of lactate gluconeogenesis.


    Be able to recognize structures of the intermediates.
    Indicate those steps that are not involved in glycolysis.
    Show the balance between NADH generation and
    utilization. Compare the production of ATP during
    anaerobic glycolysis with the requirement for ATP during
    lactate gluconeogenesis.

    3. Indicate the subcellular location of glucose


    6-phosphatase. Identify three transporters required for
    the activity of this enzyme.
    GLUCONEOGENESIS

    4. Describe the Cori cycle and the alanine cycle.


    Explain why these cycles do not lead to net glucose
    formation. Explain how net glucose formation is
    achieved during starvation.

    5. Trace how lactate, alanine, glycerol, propionate,


    galactose, and fructose are converted to glucose in the
    liver.

    6. Indicate the molecular mechanisms that can cause


    galactosemia.

    7. Illustrate the coupling between alanine


    gluconeogenesis and the urea cycle.
    GLUCONEOGENESIS

    8. Explain how fatty acid oxidation promotes


    gluconeogenesis.

    9. Explain why some amino acids are glucogenic,


    some are both glucogenic and ketogenic, and some are
    only ketogenic. Explain why palmitate is only ketogenic.

    10. Identify the regulatory enzymes of gluconeogenesis.


    Know which enzymes are regulated by allosteric
    effectors, covalent modification, and gene expression.

    11. Give the mechanism responsible for glucagon


    inhibition of glycolysis in the liver. Explain how this
    results in stimulation of gluconeogenesis by this tissue.
    GLUCONEOGENESIS

    12. Give the mechanism responsible for insulin


    stimulation of glycolysis in liver. Explain how this results
    in inhibition of gluconeogensis by this tissue.
    GLUCONEOGENESIS
    Synthesizing glucose from non carbohydrate
    precursors. The brain uses glucose as its primary fuel,
    and red blood cells use only glucose for fuel.
    Gluconeogenesis occurs mostly in liver and kidneys
    Cori and Alanine Cycles.
    Pathway of Gluconeogenesis.
    Enzymes specific to gluconeogenesis.
    Enzymes specific to gluconeogenesis.

    Fructose 1,6-bisphosphatase
    Enzymes specific to gluconeogenesis.

    Glucose-6-phosphatase
    Glucose synthesis from lactate.
    Sum: 2 Lactate + 6 ATP Glucose + 6 ADP + 6 Pi
    Synthesis of glucose from other precursors.

    Sum: 2 Alanine + CO2 +


    10 ATP Glucose +
    Urea + 10 ADP + 10 Pi
    Synthesis of glucose from other precursors.

    Urea Cycle
    Preview: Urea Cycle
    Synthesis of glucose from other precursors.

    Can we synthesize glucose from fat?


    Synthesis of glucose from other precursors.
    Synthesis of glucose from other precursors.
    Synthesis of glucose from other precursors.

    (B12)
    Synthesis of glucose from other precursors.

    Glucose formation from fructose and competing pathway of fructolysis


    Synthesis of glucose from other precursors.
    Synthesis of glucose from other precursors.
    Galactosemias.

    Classic: Severe galactose-1-P uridyltransferase


    deficiency
    Poor feeding, weight loss, vomiting, diarrhea,
    lethargy, liver dysfunction
    Cataracts in early weeks of life

    Non-classical:
    Galactokinase deficiency
    Cataracts in early weeks of life

    Non-Classical:
    Uridine diphosphate galactose 4'-epimerase\
    deficiency
    Very rare
    Presents like classic galactosemia
    Ketogenic and Glucogenic Amino Acids.
    Glucogenic amino acid Net Citric acid cycle intermediate Glucose

    Ketogenic amino acid Acetyl CoA X


    Glucose

    Ketone bodies
    Glucogenic Ketogenic Both
    Glycine Leucine Threonine
    Serine Lysine Isoleucine
    Valine Phenylalanine
    Histidine Tyrosine
    Arginine Tryptophan
    Cysteine
    Proline
    Hydroxyproline
    Alanine
    Glutamate
    Glutamine
    Aspartate
    Asparagine
    Methionine
    Regulation of Gluconeogenesis.

    Regulation combines allosteric controls, covalent phosphorylation


    and induction/repression of gene expression. Conditions
    promoting gluconeogenesis are high glucagon/low insulin.

    Main targets: Activate: 1. Pyruvate carboxylase


    2. PEP carboxykinase
    3. Fructose-1, 6-bisphosphatase
    4. Glucose-6-phosphatase

    Inactivate:
    5. Pyruvate kinase
    6. 6-phosphofructo-1-kinase
    7. Glucokinase
    8. Pyruvate dehydrogenase
    Regulation of Gluconeogenesis.

    5 1

    7
    4
    Regulation of Gluconeogenesis.

    1. Pyruvate Carboxylase
    Acetyl CoA allosteric activator
    Induced by conditions of fasting (high glucagon/low insulin)

    2. PEP Carboxykinase
    Induced by conditions of fasting (high glucagon/low insulin)

    3. Fructose-1,6-bisphosphatase
    Induced by conditions of fasting (high glucagon/low insulin)
    Activated by associated decrease in fructose-2,6-P2 and AMP

    4. Glucose-6-phosphatase
    Induced by conditions of fasting (high glucagon/low insulin)
    Regulation of Gluconeogenesis.

    5. Pyruvate kinase
    Phosphorylated and inactivated by protein kinase A
    (activated by glucagon)
    Inhibited by alanine, ATP
    Repressed by conditions of fasting (high glucagon/low insulin)

    6. 6-phosphofructo-1-kinase
    Inhibited by decreased fructose-2,6-P2 and AMP
    Coordinated with regulation of Fructose-1,6-bisphosphatase

    7. Glucokinase
    Repressed by conditions of fasting (high glucagon/low insulin)
    Inhibited by fructose-6-P
    Regulation of Gluconeogenesis.
    Alanine Lactate Fatty Acids

    FOX
    NADH
    Citric
    - 8 -
    Pyruvate Acetyl CoA Acid
    1
    - Cycle
    5 +
    X Oxaloacetate
    2 Ketone
    PEP Bodies

    F-1,6-P2
    6 X 3

    F6P

    G6P
    7 X 4

    Glucose
    Regulation of Pyruvate Dehydrogenase.
    high glucagon/insulin

    PDH
    ADP
    Inactive
    +
    PDH PDH
    - Pase
    Kinases +

    ATP Active Pi

    CoASH PDH Acetyl CoA


    Pyruvate NADH
    NAD+ CO2

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