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  • neogenesisGlycolysis and Gluco

    الفريق الطبي األكاديمي

    لكــية الطب البرشي

    البلقاء التطبيقية / املركز

    6102/6166أ حياها و من

    Done By :- Renad Aburumman

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    neogenesisGlycolysis and Gluco و من أحياها

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    Biochemistry of Carbohydrates

    The figure represent the overall carbohydrate metabolic

    reaction that start glucose which glycolysis to pyruvate

    Using 2 ATP,2NADH and in the presense of O2 they will

    enter citric acid cycle (aerobic oxidation )and convert to

    CO2 +H2O ,2NAD +, 30-38 ATP by the oxidative

    phosphorylation, And without O2 (anaerobic)

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    (fermentation) they will convert to Lactate in ANIMALS

    but in yeast, bacteria they will convert to 2CO2+2Ethanol

    and only 2ATP.

    Therefore, what we notes here that there is from 15to

    19 increasing in ATP aerobic oxidation (30-38) VS

    anaerobic oxidation (2).

    Which is better for losing weight, aerobic or anaerobic

    oxidation? Anaerobic, because we are going to oxidize

    a lot of Glucose to produce enough of ATP.

    Glycolysis • The Breakdown of Glucose

    • Primary Energy Source of Cells

    • Central Metabolic Pathway

    • All Reactions Occur in Cytoplasm

    • Two Phases

    • Produces 2Pyruvates, 2 ATP, 2 NADH

    • Regulation

    Phase 1

    ATP Investment

    ATP ADP

    ATP ADP

    Phase 2

    Energy Production

    2ADP 2ATP

    2ADP 2ATP

    2 NAD+ 2NADH

    This pathway is important because it is the central

    pathway to energy production.

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    Glucose is not found free in our muscle but its stored as

    glycogen, once your body need glucose the glycogen will

    Be degrade and glucose will be produced immediately

    although fatty acid will be oxidized they will provide

    more energy than glucose because they are not

    dissolved easily in blood to be transported to your

    muscles like glucose.

    Every cell must do glycolysis because it regulates

    metabolism, and without it metabolism will stop.

    All reactions of glycolysis occur in cytoplasm but other

    pathways of citric acid cycle take place in mitochondria.

    Other metabolic pathways such as gluconeogenesis,

    which has two places, one in mitochondria and the

    other one in cytoplasm.

    Glycolytic pathway could be divided into two phases. In

    Phase 1 the reactions require ATP in order to Start

    oxidizing, (in glycolysis there is only one oxidation

    reaction and it is completed when CO2 and H2O in citric

    acid cycle).

    In phase 2, there is ATP production.

    The net production of the two phases is two ATP

    molecules

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    Glycolysis • Glucose

    • Stored in Polymers (Amylose/Amylopectin/Glycogen)

    • poison

    • Readily Released

    • Travels Easily in Blood

    • Made from Simple Precursors (Gluconeogenesis)

    Glycolysis: the oxidation of glucose.

    Phase 1

    • Regulated Step of Glycolysis

    • ΔG°’ = -16.7 kJ/mol

    Glucose

    Hexokinase

    Glucose-6-Phosphate (G6P)

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    First reaction .

    Hexokinase:

     Hexo= Work on substrate of six carbon atoms.

     Kinase = phosphorylation.

     Phosphorylation---> Glucose, fructose, galactose

     Inhibited by G6P.

     Low Km.

    Phosphorylation is important because you are trapping

    glucose in cell and preventing it from going back to blood

    cycle.

    Phosphate group will be transferred into the Carbon

    number 6.

    Glycolysis

    Hexokinase

    • Found in Virtually All Cells

    • Hexokinase is Not Specific for Glucose

    • Glucokinase - Higher Km

    ATP

    Glucose

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    • Inhibited by G6P Product

    Glucokinase is another Enzyme that is specific to glucose

    only found in liver induce by insulin unlike Hexokinase.

    Induction means that insulin will stimulate the synthesis

    of Glucokinase and the synthesis of other enzymes is

    one of the regulatory steps in metabolism and when you

    synthesis more of this enzyme you are activating it.

    (18:45)**

    In the figure, we noticed very big enzyme and very tiny

    substrate so enzyme is important, how? it will help

    these small substrate to find each other and start

    catalyzing and without Enzymes the reaction will not

    take place.

    Hexokinase

    Substrates

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    7 reaction reversible &3 reactions irreversible.

    2nd

    Enzymatic

    reaction

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    high (-) ^G, one direction ,irreversible.

    Seven reactions out of ten of the glycolysis are

    reversible.

    Regulation of PFK1 is important so that ATP (substrate)

    regulate the enzyme. How? At low concentration of

    ATP, the enzyme is very active and at high ATP

    concentration, the enzyme will be inhibited, why?

    Because the purpose of glycolysis is to produce energy,

    so if we have excess of energy in the form of ATP the

    glycolysis will shut off.

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    How does the same molecule at low concentration act

    as activator, but at high concentration act as inhibitor?

    Because of Different sites of binding. At high

    concentration, it binds to regulatory site and shift it to

    right (T state, low affinity to substrate).

    When F6P convert to F1, 6BP the reaction must continue

    to the end.

    Transporting phosphate group into the Carbon number

    1.

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    F2, 6BP is the most Important regulator of carbohydrate

    glycolysis but it is not an Intermediate in glycolytic

    pathway .

    Why is AMP positive (activator) regulator to PFK1? AMP

    presents in low energy state but ATP presents in high-

    energy state.

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    Why is ΔG’° odd?

    Because it is reversible, highly positive and in order to

    make this reaction go forward the cell have to make ^G

    negative, how? Next slide…

    Two half each one have 3

    carbon

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    In order to make this reaction happen in forward pathway, the cell has to maintain ^G negative, by making less logarithmic term more negative than 23.9, how? By increasing the concentration of the reactants and decreasing the concentration of products. As much as negative quantities we have, as much as negative ^G.

    It does that by pushing and pulling. Pushing of reactants to be in high concentration, and pulling of products to be in law concentration. (the pushing and pulling mechanisms)

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    Because glycolysis must continue, the cell is being very active in producing F-1,6BP and it will accumulate at high (+) ^G and this high [F1,6BP] is used by the cell as an activator for the last step of glycolysis which is pyruvate kinase (that will convert phosphoenolpyruvate to pyruvate), (phosphoenolpyruvate coming from GA1P,GA3P,dihydroxyacetone phosphate(DHAP),2PG)so When this enzyme is activated by this feed forward activation, the product will be absorbed and taken out and thus will decrease the products and increase the reactants, thus we will have the ^G negative, and the Reaction will go forward.

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    Triose Phosphate Isomerase  Not regulatory but

    important which is controlled by diffusion of substrate.

    Perfect enzyme  the enzymes that regulated substrate diffusion & work Very fast.

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    All dehydrogenizes (enzyme) require coenzyme NAD or FAD, and Pi.

    Conversion of oxidation of aldehyde to Ester(carboxylic group stifled to phosphate), usually in order to bond

    Very toxic to cell s