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    Glycolysis Gluconeogenesis

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    jaleemjames
    Glycolysis is a 10 step pathway that breaks down glucose to produce energy in the form of ATP and the reduced molecule NADH. It occurs in the cytosol of cells and can proceed aerobically or anaerobically. Glucose first enters cells via glucose transporter proteins and is phosphorylated by hexokinase in the energy investment phase. It is then broken down by multiple phosphorylation and cleavage reactions in the splitting phase. In the payoff phase, pyruvate is produced and can be converted to lactate anaerobically or acetyl-CoA aerobically through entry into the citric acid cycle to further oxidize and produce ATP. Glycolysis is tightly regulated by enzymes like

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    Glycolysis Gluconeogenesis

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    jaleemjames
    18 views29 pages
    Glycolysis is a 10 step pathway that breaks down glucose to produce energy in the form of ATP and the reduced molecule NADH. It occurs in the cytosol of cells and can proceed aerobically or anaerobically. Glucose first enters cells via glucose transporter proteins and is phosphorylated by hexokinase in the energy investment phase. It is then broken down by multiple phosphorylation and cleavage reactions in the splitting phase. In the payoff phase, pyruvate is produced and can be converted to lactate anaerobically or acetyl-CoA aerobically through entry into the citric acid cycle to further oxidize and produce ATP. Glycolysis is tightly regulated by enzymes like

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    Glycolysis Gluconeogenesis Lecture Slides

    Original Title

    Glycolysis Gluconeogenesis

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    Glycolysis is a 10 step pathway that breaks down glucose to produce energy in the form of ATP and the reduced molecule NADH. It occurs in the cytosol of cells and can proceed aerobically or anaerobically. Glucose first enters cells via glucose transporter proteins and is phosphorylated by hexokinase in the energy investment phase. It is then broken down by multiple phosphorylation and cleavage reactions in the splitting phase. In the payoff phase, pyruvate is produced and can be converted to lactate anaerobically or acetyl-CoA aerobically through entry into the citric acid cycle to further oxidize and produce ATP. Glycolysis is tightly regulated by enzymes like

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    18 views29 pages

    Glycolysis Gluconeogenesis

    Uploaded by

    jaleemjames
    Glycolysis is a 10 step pathway that breaks down glucose to produce energy in the form of ATP and the reduced molecule NADH. It occurs in the cytosol of cells and can proceed aerobically or anaerobically. Glucose first enters cells via glucose transporter proteins and is phosphorylated by hexokinase in the energy investment phase. It is then broken down by multiple phosphorylation and cleavage reactions in the splitting phase. In the payoff phase, pyruvate is produced and can be converted to lactate anaerobically or acetyl-CoA aerobically through entry into the citric acid cycle to further oxidize and produce ATP. Glycolysis is tightly regulated by enzymes like

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    of 29

    Glycolysis

    CARBOHYDRATE METABOLISM – TOPIC 1


    Objectives

    • Students should be able to:


    • State the significance of glycolysis in living cells
    • Describe how glucose enters the liver and peripheral tissues
    • Describe the phases of glycolysis
    • Should be able to explain the importance of :
    • The committed step in glycolysis
    • Key intermediates in the glycolytic pathway which are also
    common intermediates in other metabolic pathways
    • Identify the irreversible steps in glycolysis
    • Identify the steps where ATP is utilized
    • Identify the steps where ATP and NADH are synthesized
    • Describe the fates of pyruvate and explain how it is utilized to
    synthesize ATP under aerobic and anaerobic conditions
    • Describe how other sugars enter the glycolytic pathway
    Glycolysis

    • also called Embden-Meyerhof pathway (E.M-Pathway).


    • It occurs in cytosol
    • 10 step catabolic pathway
    • Objective of pathway
    • to produce energy (ATP) and the reducing agent (NADH) from
    catabolizing hexose sugars
    • Can occur aerobically or anaerobically
    Sources of
    Carbohydrates
    • Glycolysis is a major pathway for ATP
    synthesis in tissues lacking mitochondria -
    erythrocytes, cornea, lens etc.
    Importance • Glycolysis is very essential for brain tissues
    of Glycolysis which is dependent on glucose for energy.
    • Independently, it can catabolize carbs
    anaerobically unlike many other energy
    yielding substrates
    • Glycolysis is a central metabolic pathway
    • Many of its intermediates are primary
    substrates or shared intermediates for
    other pathways e.g. glycogen synthesis, the
    Pentose Phosphate Pathway, fatty acid
    synthesis, amino acid synthesis etc.
    • Glucose transporters (GLUT) are transmembrane
    proteins that facilitate entry into cells - bidirectional
    • GLUT -1
    • Found in all cells of the body
    Glucose • Blood glucose level is ~5mM but this transporter
    has a KM of 1mM – high affinity for glucose
    Entry Into • GLUT – 3
    Cells • Similar to GLUT-1
    • Found in neural tissue in the brain
    • GLUT – 2
    • Found primarily in the β-cells of the pancreas but
    also in liver, kidney and intestines
    • Has a high Km value (~15mM) which means
    pancreas will only respond to glucose in high conc
    • GLUT-4
    • Found in muscle, heart and adipose tissue
    • Sensitive to insulin – causes increased production
    and presence in membrane
    • Km = 5mM.
    Entry of Glucose into Cells
    Phases of Glycolysis
    • Divided into three distinct
    phases.
    1. Energy investment phase
    or priming phase
    2. Splitting phase
    3. Payoff phase.
    Energy Investment & Splitting Phases

    • Glucose is obtained
    from diet via intestinal
    hydrolysis of lactose,
    sucrose, maltose,
    glycogen, or starch

    • Can be synthesized in
    the liver from non-
    glucose precursors and
    released into the blood
    to be used by other
    tissues
    • Phosphorylated sugar molecules do not
    readily penetrate cell membranes without
    specific carriers
    • this commits glucose to further metabolism
    in the cell.
    • One of 3 key regulatory enzymes of glycolysis.
    Hexokinase • Hexokinase
    • Allosterically inhibited by glucose-6-PO4
    Reaction • Allosterically stimulated by Pi
    • Step is irreversable
    Hexokinase vs Glucokinase
    Phosphofructokinase Reaction

    • Fructose 6- phosphate is phosphorylated to Fructose-1, 6-


    bisphosphate by Phosphofructokinase (PFK-1)
    • The PFK reaction is the rate-limiting step.
    • Enzyme allosterically activated by ADP and AMP conc
    • Inhibited by ATP and citrate (high energy)
    • Irreversible reaction
    PFK2 and Regulation
    The
    Payoff
    Phase
    Regulation of Pyruvate Kinase
    Regulation of Pyruvate Kinase
    Fates of Pyruvate
    Energetic Fates of Pyruvate
    Fates of Pyruvate – Acetyl CoA

    • In the presence of O2 pyruvate enters the mitochondria


    (outer – aquaporin, inner – pyruvate translocase in symport
    with H+)
    • Where it is oxidatively decarboxylated to acetyl CoA and
    enters the TCA
    Aerobic Fate of Pyruvate
    Fates of Pyruvate - Lactate

    • During glycolysis NAD+ is reduced NADH

    • NADH in the cytosol is limited

    • Problem – without oxygen NADH cannot be re-oxidized back to


    NAD+ and glycolysis will stop

    • Solution:
    Fates of
    Pyruvate -
    Lactate
    Summary
    Gluconeogenesis
    • Gluco – sugar (think glucose)
    • Neo – new
    • Genesis – origin

    • Pathway synthesizes glucose from non-


    carbohydrate precursors namely:
    • Alcohols – glycerol
    • Amino acids
    • Lactate
    • pyruvate
    Entry of Gluconeogenic Substrates
    Entry of Amino Acids into
    Gluconeogenesis
    Gluconeogenesis – Bypass
    Reactions
    • Glycolysis has 3
    irreversible
    reactions
    • In order to
    synthesize glucose,
    these reactions
    must be bypassed
    Reciprocal
    Regulation of
    Glycolysis &
    Gluconeogenesis

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