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    Tca Cycle

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    fatimamuzammil406
    The citric acid cycle involves a series of chemical reactions that occur in the mitochondria of cells. It is the final common pathway for oxidation of fuel molecules like carbohydrates, fats, and proteins. During the cycle, acetyl groups from carbohydrates, fats, and proteins are oxidized, producing carbon dioxide and electron carriers NADH and FADH2 that fuel the electron transport chain. The cycle regenerates oxaloacetate from succinate so that the cycle can continuously oxidize acetyl groups and produce reduced electron carriers to generate ATP through oxidative phosphorylation.

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    Tca Cycle

    Uploaded by

    fatimamuzammil406
    13 views29 pages
    The citric acid cycle involves a series of chemical reactions that occur in the mitochondria of cells. It is the final common pathway for oxidation of fuel molecules like carbohydrates, fats, and proteins. During the cycle, acetyl groups from carbohydrates, fats, and proteins are oxidized, producing carbon dioxide and electron carriers NADH and FADH2 that fuel the electron transport chain. The cycle regenerates oxaloacetate from succinate so that the cycle can continuously oxidize acetyl groups and produce reduced electron carriers to generate ATP through oxidative phosphorylation.

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    Tca

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    The citric acid cycle involves a series of chemical reactions that occur in the mitochondria of cells. It is the final common pathway for oxidation of fuel molecules like carbohydrates, fats, and proteins. During the cycle, acetyl groups from carbohydrates, fats, and proteins are oxidized, producing carbon dioxide and electron carriers NADH and FADH2 that fuel the electron transport chain. The cycle regenerates oxaloacetate from succinate so that the cycle can continuously oxidize acetyl groups and produce reduced electron carriers to generate ATP through oxidative phosphorylation.

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

    Tca Cycle

    Uploaded by

    fatimamuzammil406
    The citric acid cycle involves a series of chemical reactions that occur in the mitochondria of cells. It is the final common pathway for oxidation of fuel molecules like carbohydrates, fats, and proteins. During the cycle, acetyl groups from carbohydrates, fats, and proteins are oxidized, producing carbon dioxide and electron carriers NADH and FADH2 that fuel the electron transport chain. The cycle regenerates oxaloacetate from succinate so that the cycle can continuously oxidize acetyl groups and produce reduced electron carriers to generate ATP through oxidative phosphorylation.

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    © All Rights Reserved
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    of 29

    TCA CYCLE

    Introduction
    •The citric acid cycle is the central
    metabolic hub of the cell.
    •It is the final common pathway for the
    oxidation of fuel molecule such as amino acids,
    fatty acids, and carbohydrates.
    •I n eukaryotes, the reactions of the citric acid
    cycle take place inside mitochondria, in contrast
    with those of glycolysis, which take place in the
    cytosol.
    Alcoholic Fermentation
    Acetyl CoA from Pyruvate
    Overview of the Citric Acid
    Cycle
    The citric acid cycle (Krebs cycle, tricarboxylic
    acid cycle) includes a series of oxidation-
    reduction reactions in mitochondria that
    result in the oxidation of an acetyl group to
    two molecules of carbon dioxide and reduce
    the coenzymes that are reoxidized through
    the electron transport chain, linked to the
    formation of ATP.
    Overview of the Citric Acid
    Cycle
    A four- carbon compound (oxaloacetate) condenses
    with a two-carbon acetyl unit to yield a six-carbon
    tricarboxylic acid (citrate).
    An isomer of citrate is then oxidatively
    decarboxylated.
    The resulting five-carbon compound (α-ketoglutarate)
    also is oxidatively decarboxylated to yield a four
    carbon compound (succinate).
    Oxaloacetate is then regenerated from succinate.
    Two carbon atoms enter the cycle as an acetyl unit
    and two carbon atoms leave the cycle in the form of
    two molecules of carbon dioxide.
    Overview of the Citric Acid Cycle
    o Three hydride ions (hence, six
    electrons) are transferred to
    three molecules of
    nicotinamide adenine
    dinucleotide (NAD+), whereas
    one pair of hydrogen atoms
    (hence, two electrons) are
    transferred to one molecule of
    flavin adenine dinucleotide
    (FAD) .
    o The function of the citric acid
    cycle is the harvesting of
    high- energy electrons from
    carbon fuels.
    Citric acid cycle and requirement of
    oxygen

    Oxygen is required for the citric acid cycle indirectly in as


    much as it is the electron acceptor at the end of the
    electron- transport chain, necessary to regenerate NAD+ and
    FAD.
    Citric acid cycle and requirement of
    oxygen (contd.)
    o The citric acid cycle itself neither generates a large amount of
    ATP nor includes oxygen as a reactant.
    o Instead, the citric acid cycle removes electrons from acetyl
    CoA and uses these electrons to form NADH and FADH2 .
    o In oxidative phosphorylation, electrons released in the
    reoxidation of NADH and FADH2 flow through a series of
    membrane proteins (referred to as the electron-transport
    chain) to generate a proton gradient across the membrane
    o The citric acid cycle, in conjunction with oxidative
    phosphorylation, provides the vast majority of energy used
    by aerobic cells in human beings, greater than 95%.
    Role of oxaloacetate in citric acid cycle
    • The four-carbon molecule, oxaloacetate that
    initiates the first step in the citric acid cycle is
    regenerated at the end of one passage through
    the cycle.
    • The oxaloacetate acts catalytically: it
    participates in the oxidation of the acetyl
    group but is itself regenerated.
    • Thus, one molecule of oxaloacetate is capable
    of participating in the oxidation of many
    acetyl molecules.
    Reactions of the Citric Acid Cycle
    • Step-1 Formation of Citrate- The citric acid
    cycle begins with the condensation of a four-
    carbon unit, oxaloacetate, and a two-carbon
    unit, the acetyl group of acetyl CoA.
    Oxaloacetate reacts with acetyl CoA and H2O
    to yield citrate and CoA.
    Step-1-Formation of Citrate

    Oxaloacetate first condenses with acetyl CoA


    to form citryl CoA, which is then hydrolyzed to
    citrate and CoA.
    Step-2-Formation of Isocitrate

    • Citrate is isomerized into isocitrate to enable


    the six-carbon unit to undergo oxidative
    decarboxylation.
    The isomerization of citrate is accomplished by
    a dehydration step followed by a hydration
    step.
    Step-2-Formation of Isocitrate
    Step-3- Formation of α- Keto
    Glutarate
    Isocitrate undergoes dehydrogenation catalyzed by
    isocitrate dehydrogenase to form, initially, Oxalo
    succinate, which remains enzyme-bound and
    undergoes decarboxylation to α -ketoglutarate.
    The decarboxylation requires Mg++or Mn++ions.
    There are three isoenzymes of isocitrate
    dehydrogenase.
    One, which uses NAD+, is found only in
    mitochondria.
    The other two use NADP+ and are found
    in mitochondria and the cytosol.
    Step-3- Formation of α- Keto Glutarate

    Respiratory chain-linked oxidation of


    isocitrate proceeds almost completely
    through the NAD+-dependent
    enzyme.
    Step-4-Formation of Succinyl Co
    A
    o α-Ketoglutarate undergoes oxidative
    decarboxylation in a reaction catalyzed by a
    multi-enzyme complex similar to that involved
    in the oxidative decarboxylation of pyruvate.
    o The α--ketoglutarate dehydrogenase
    complex requires the same cofactors as the
    pyruvate dehydrogenase complex—thiamine
    diphosphate, lipoate, NAD+, FAD, and CoA—
    and results in the formation of succinyl-CoA.
    Step-4-Formation of Succinyl Co A

    The conversion of isocitrate into α-


    ketoglutarate is followed by a second
    oxidative decarboxylation reaction, the
    formation of Succinyl CoA from α-
    ketoglutarate.
    Step-5- Formation of Succinate
    • Succinyl CoA is an energy-rich thioester
    compound
    • The cleavage of the thioester bond of succinyl
    CoA is coupled to the phosphorylation of a
    purine nucleoside diphosphate, usually GDP.
    • This reaction is catalyzed by succinyl CoA
    synthetase (succinate thiokinase).
    Step-5- Formation of Succinate

    o This is the only example in the citric acid cycle


    of substrate level phosphorylation.
    Tissues in which gluconeogenesis occurs (the liver
    and kidney) contain two isoenzymes of succinate
    thiokinase, one specific for GDP and the other for
    Step-5- Formation of Succinate
    • The GTP formed is used for the
    decarboxylation of oxaloacetate to
    phosphoenolpyruvate in gluconeogenesis, and
    provides a regulatory link between citric acid
    cycle activity and the withdrawal of
    oxaloacetate for gluconeogenesis.
    • Nongluconeogenic tissues have only the
    isoenzyme that uses ADP.
    Step-6- Formation of
    Fumarate
    • The first dehydrogenation reaction, forming
    fumarate, is catalyzed by succinate
    dehydrogenase, which is bound to the inner
    surface of the inner mitochondrial membrane.
    • The enzyme contains FAD and iron-sulfur
    (Fe:S) protein, and directly reduces
    ubiquinone in the electron transport chain.
    Step-7- Formation of
    Malate
    Fumarase (fumarate
    hydratase) catalyzes
    the addition of water
    across the double
    bond of fumarate,
    yielding malate.
    Step-8- Regeneration of
    oxaloacetate
    • Malate is converted to oxaloacetate by
    malate dehydrogenase, a reaction requiring
    NAD+.
    • Although the equilibrium of this reaction
    strongly favors malate, the net flux is to
    oxaloacetate because of the continual
    removal of oxaloacetate (to form citrate, as a
    substrate for gluconeogenesis, or to undergo
    transamination to aspartate) and also the
    Step-8- Regeneration of
    oxaloacetate
    TCA
    CYCLE

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