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    The document summarizes key aspects of bioenergetics and cellular respiration. It describes how mitochondria use catabolic pathways to convert the chemical energy in food into ATP through oxidative phosphorylation. The citric acid cycle and electron transport chain generate NADH and FADH2, which carry electrons and protons. As these electrons are passed through protein complexes embedded in the mitochondrial inner membrane, protons are pumped from the matrix to the intermembrane space, creating an electrochemical gradient. ATP synthase uses this proton gradient to phosphorylate ADP, coupling electron transport to ATP production.

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    The document summarizes key aspects of bioenergetics and cellular respiration. It describes how mitochondria use catabolic pathways to convert the chemical energy in food into ATP through oxidative phosphorylation. The citric acid cycle and electron transport chain generate NADH and FADH2, which carry electrons and protons. As these electrons are passed through protein complexes embedded in the mitochondrial inner membrane, protons are pumped from the matrix to the intermembrane space, creating an electrochemical gradient. ATP synthase uses this proton gradient to phosphorylate ADP, coupling electron transport to ATP production.

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    Bioenergetics

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    The document summarizes key aspects of bioenergetics and cellular respiration. It describes how mitochondria use catabolic pathways to convert the chemical energy in food into ATP through oxidative phosphorylation. The citric acid cycle and electron transport chain generate NADH and FADH2, which carry electrons and protons. As these electrons are passed through protein complexes embedded in the mitochondrial inner membrane, protons are pumped from the matrix to the intermembrane space, creating an electrochemical gradient. ATP synthase uses this proton gradient to phosphorylate ADP, coupling electron transport to ATP production.

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    159 views27 pages

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    Uploaded by

    YoAmoNYC
    The document summarizes key aspects of bioenergetics and cellular respiration. It describes how mitochondria use catabolic pathways to convert the chemical energy in food into ATP through oxidative phosphorylation. The citric acid cycle and electron transport chain generate NADH and FADH2, which carry electrons and protons. As these electrons are passed through protein complexes embedded in the mitochondrial inner membrane, protons are pumped from the matrix to the intermembrane space, creating an electrochemical gradient. ATP synthase uses this proton gradient to phosphorylate ADP, coupling electron transport to ATP production.

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    Bioenergetics
     Living cells are in a dynamic state maintained by metabolism
     catabolism is to supply energy while anabolism is for energy storage
     purpose of catabolic pathways is to convert the chemical energy in
    food to molecules of ATP
     the mitochondria are the sites of catabolic pathways which yield ATP
     it is made of 2 membranes
    outer = permeable to small molecules and ions
    = no transporting membrane proteins
    = not folded
    inner = resistant to penetration of any ions and most uncharged
    molecules
    = transport membrane proteins abound for transfer of materials
    = highly folded
     All mitochondrial enzymes are synthesized in the cytosol
    translocator outer membrane (TOM) channels
    where enzymes cross into the intermembrane space

     chaperone-like translocator inner membrane (TIM) complexes


    accepts and inserts enzymes into the inner membrane

     enzymes are located only inside the inner membrane, thus, substrates
    must pass the 2 membranes ----- products leave the same way

     matrix is the inner nonmembranous portion of the mitochondrion


    where enzymes for the citric acid cycle are located

     the cristae (infoldings) project into the matrix and is the locale of
    enzymes involved in the oxidative phosphorylation
    THE COMMON CATABOLIC PATHWAY
     Has 2 parts
    1. Citric acid cycle (TCA cycle or Krebs cycle)
    2. Oxidative phosphorylation (electron transport chain, phosphorylation)

    A. Agents for storage of energy and transfer of phosphate groups


    AMP --- contain heterocyclic amine adenine and D-ribose
    ADP --- sugar joined together by N-glycosidic bond
    ATP --- to form adenosine; further linked to Pi

     when one phosphate group is hydrolyzed from each of these…


    ATP = 7.3 kcal/mol
    ADP = 7.3 kcal/mol
    AMP = 3.4 kcal/mole
     ATP molecules in the cells do not normally last longer than about 1 minute,
    thus, a high turnover rate (40 kg ATP/day is manufactured and degraded
    B. Agents for transfer of electrons in biological redox
    reactions
    – coenzymes, NAD+ and FAD, both contain an ADP core in the
    structure which is the link of the coenzyme to the apoenzyme

    NAD+= +charge is due to the nitrogen


    =operative part is the nicotinamide part which gets
    H+ and e-
    reduced
    transporting
    molecules FAD=operative part is the flavin part which gets reduced

    reduced forms are NADH AND FADH2


    C. Agent for transfer of acetyl groups
    – CoA is the acetyl-transporting molecules linked via a
    thioester bond (high energy bond) 7.51 kcal/mol
    – CoA contain ADP linked to pantothenic acid and
    mercaptoethylamine
    – active part is mercaptoethylamine
    o
    CH3 - c - s - CoA
    Citric acid cycle
     Common catabolism of carbohydrates and lipids
    begins when they are broken down into 2-carbon
    products (acetyl units)
     transported by CoA as acetylCoA C 2

    Step 1 C6
    C4

    •acetylCoA enters the cycle by combining with CO2


    a C4 compound called oxaloacetate to produce C5
    citrate
    • addition of -CH3 group of acetylCoA to the C4
    C=O of the oxaloacetate
    • hydrolysis of the thioester to produce the C6 C2
    compound citrate Carbon balance
    • enzyme used is citrate synthase
    Step 2
     citrate ion is dehydrated to cis-aconitate
     cis-aconitate is hydrated back to isocitrate
     enzyme used is aconitase

    Step 3
     isocitrate is oxidized to produce oxalosuccinate and decarboxylated
    at the same time to produce a C5 -ketoglutarate (can be made into
    glutamic acid)
     enzyme used is ICD
     required NAD+
    Steps 4 and 5
     removal of another CO2 from -KG to produce succinate
    (C4)
     uses a complex enzyme system
     production of a high energy compound, GTP

    Step 6
     succinate is oxidized by FAD to produce fumarate (by
    removal of 2 hydrogen)
     fumarate has a trans-double bond
     enzyme used is succinate dehydrogenase
    Step 7
     fumarate is hydrated to give the malate ion (C 4)
     enzyme used is fumarase

    Step 8
     final step is the oxidation of malate by NAD + to give
    oxaloacetate
     enzyme used is malate dehydrogenase
     An acetyl unit enters the TCA cycle and 2 CO2 molecules are given off
    How does the TCA cycle produce energy?
    – Production of GTP
    – most of the energy is produced via reactions that convert NAD+ to
    NADH and FAD to FADH2
    – NADH and FADH2 carries the e- and H+ that will produce ATP in
    mitochondrion
     Stepwise degradation and oxidation of acetate in the TCA cycle for
    most efficient extraction of energy
     Other advantages of the TCA cycle

    1. By-products provide raw materials for amino acid synthesis as


    per need
    2. The many-component cycle provides an excellent method for
    regulating the speed of catabolic reactions
     In summary, the overall reactions in the TCA
    cycle:
    GDP + Pi + CH3 - CO - S - CoA + 2H2O + 3NAD+ + FAD

    (exhaled)

    CoA + GTD + 2CO2 + 3NADH + FADH2 + 3H+


     feedback mechanism occurs when
    NADH + H+ accumulates - inhibit steps 1, 3 and 4
    ATP accumulates - inhibit steps 1, 3 and 4
    acetylCoA is in abundance - cycle accelerates
    presence of ADP and NAD+ - stimulates ICD
    ELECTRON and H+ TRANSPORT

     The reduced coenzymes, NADH and FADH2, are end products


    of the TCA cycle

     they carry H+ and e-, thus, have the potential to yield energy
    when these combine with oxygen to form water
    EXO 4 H+ + 4e- + O2 2H2O + energy

     involves a number of enzymes embedded in the inner


    membrane of mitochondria arranged in an (assembly line)
    increasing affinity for e-
    The sequence of the electron - carrying enzyme systems starts with

    Complex I
     largest complex
     some 40 subunits, among them a flavoprotein and
    several FeS clusters
     CoQ or ubiquinone is associated with complex I
     oxidizes the NADH produced in the citric acid cycle
    and reduces the CoQ
    NADH + H+ + CoQ -- NAD+ + CoQH2
     some of the energy released in this reaction is used
    to move 2H+ across the membrane (matrix to
    intermembrane space)
    Soluble in lipid,
    thus, can move
    laterally within
    the membrane
    Complex II
     also catalyzes the transfer of e- to CoQ from
    the oxidation of succinate in the TCA cycle,
    producing FADH2

     energy derived from this is not enough to


    pump two protons across the membrane nor
    a channel for such transfer is possible
    Complex III
     an integral membrane complex contains 11 subunits, including cytochrome b,
    cytochrome C1 and FeS clusters

     delivers the e- from CoQH2 to cytochrome c

     the complex has 2 channels through which two H+ are pumped from CoQH2
    into the intermembrane space

     since each cyt c can pick up only electron, 2 cytochrome c’s are needed:

    CoQH2 + 2 cyt c (reduced)

    CoQ + 2H+ + 2 cytochrome c (oxid)

     each cytochrome has an iron-ion-containing heme center embedded in its own


    protein and the letters used to designate them were given in order of their
    discovery
    Complex IV
     known as cytochrome oxidase, contains 13 subunits-most importantly,
    cyt 3, a heme that has an associated copper center

     an integral membrane protein complex

     e- moves from cyt c  cyt a  cyt 3  cleavage of O-O bond

     oxidized form of the enzyme takes up two H+ from the matrix for each
    oxygen atom forming H2O which is released into the matrix
    1/2 O2 + 2H+ + 2e- -- H2O

     during this process, two more H+ are pumped out of the matrix and into
    the intermembrane space (energy driving this process comes from the
    energy of water formation)

     this final pumping into the intermembrane space makes a total of


    6H+/NADH + H+ and 4H+/FADH2 molecules
    PHOSPHORYLATION AND THE CHEMIOSOMOTIC PUMP

    CHEMIOSMOTIC THEORY by Mitchell


    proposed that the electron transport is accompanied
    by an accumulation of protons in the intermembrane
    space of the mitochondrion, which in turn,

    creates an osmotic pressure

    protons driven back to mitochondrion under this


    pressure generate ATP
    How do the e- and H+ transports produce the chemical
    energy of ATP?
    The energy in the e- transfer chain creates a proton gradient

    Spontaneous flow of ions from a A continuous variation in the


    region of high concentration to a H+ conc along a given region
    region of low concentration results
    in a driving force that propels the
    protons back to the mitochondrion  H+ conc in intermembrane
    through the proton translocating space than matrix
    ATPase in the inner membrane of
    mitochondrion catalyzing
    ATPase
    ADP + Pi ATP + H2O
     Proton translocating ATPase is a complex “rotor
    engine” made of 16 different proteins
    – has Fo sector, embedded in the membrane, contains the
    proton channel
    – the proton channel composed of 12 subunits rotate every
    time a proton passes from the cytoplasmic side
    (intermembrane) to the matrix side of the mitochondrion

    rotation is transmitted to the F1 sector “rotor”

    - F1 sector contains 5 kinds of • Rotor (γ &  subunits)


    • catalytic unit ( &  subunits)
    polypeptides surrounds the rotor & makes the
    - the F1 catalytic unit converts the ATP
    mechanical energy of the rotor to • stator unit () for stability of
    chemical energy of the ATP the whole complex
    molecule
    OUTER

    INNER
    INTERMEMBRANE SPACE
    A molecule of
    ATP synthesized / pair of translocated H+
    Accumulated H+ storage of electrical energy (due to flow of charges)
    in the form of chemical energy

    Pump H+ out Hydrolysis of ATP

    • ONLY when the two parts of the proton translocating ATPase, F 1


    and Fo, are linked is energy production possible

    • disruption of the interaction between F1 and Fo is disrupted –


    energy transduction is lost
     Protons that enter a mitochondrion combine with the electrons
    transported through the electron transport chain and with oxygen to form
    water
    Electron/H+ transport Each O2 molecule
     the net result of the two processes ATP formed
    we breathe in

    2H2O Combines with 4H+


    ions & 4 e-

     The oxygen has two functions


    Coming from the
    1. Oxidize NADH to NAD+ and FADH2 to FAD so that NADH and FADH2
    these molecules can go back and participate in the molecules (TCA
    TCA cycle cycle

    2. Provide energy for the conversion of ADP to ATP


    which is indirectly accomplished
    ATP formation is driven by the entrance of H+ into the mitochondrion

    HOH from O2 ------- increase in H2O depleted the H+ conc

    O2 is not utilized but is needed for cell’s survival !


     The overall reactions in oxidative phosphorylation is

    NADH + 3ADP + 1/2 O2 + 3Pi + H+ NAD+ + 3ATP + H2O

    FADH2 + 2ADP + 1/2 O2 + 2Pi FAD + 2ATP + H2O


    THE ENERGY YIELD
     The energy released during electron transport is now finally built into the ATP molecule
     each pair of protons entering a mitochondrion results in the production of one ATP
    molecule
     for each NADH molecule, we get 3 ATP molecules
     for each FADH2 molecule, only 4 protons are pumped out of the mitochondrion, thus,
    only 2 ATP molecules are produced for each FADH2
     combining the TCA cycle and oxidative phosphorylation:
    – for each c2 fragment entering the TCA cycle
    A. we obtain 3NADH x 3ATP/NADH = 9ATP
    1FADH2 x 2ATP/FADH2 = 2ATP
    1GTP = 12ATP

    B. uses up to 2O2 molecules


    one c2 fragment is oxidized with two molecules of O2 to produce two molecules
    c2 + 2O2 + 12 ADP + 12 Pi 12 ATP + 2CO 2
    COMPARISON OF CHEMICAL ENERGY TO OTHER FORMS OF ENERGY
     Activity of many enzymes is controlled and regulated by
    phosphorylation
    Phosphorylase b Phosphorylase (seryl-PO4)

    ATP ADP
    Glycogen glucose

    Body maintains a high conc of K+ inside the cells, low outside the cells
    – the reverse is true for Na+
    – special transport proteins in the cell membranes constantly pump K+
    into and Na+ out of the cells
    – pumping requires energy via hydrolysis of ATP to ADP
    – with this pumping, the charges in and out of the cell are unequal which
    generates electrical potential
    – chemical energy of ATP is transformed into electrical energy which
    operates in neurotransmission
     ATP is the immediate source of energy in muscle contraction
    – as ATP binds to myosin the actin-myosin complex
    (contracted muscle) dissociates and the muscle relaxes
    – when myosin hydrolyses ATP, it interacts with actin once
    more, and new contraction occurs

     a molecule of ATP upon hydrolysis to ADP yields 7.3 kcal/mol


    = some of this energy is released as heat and used to maintain
    body temperature.
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