Koster text: Life5th Edition - Purves..: Read Chapter 7 for this lecture

General Biology2 Spring 2000

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CELLULAR RESPIRATION

Living systems depend on an input of energy to fuel the reactions that constitute life.  Remember that ATP is the molecule that cells use for short-term energy.  ATP carries a useful amount of energy within its molecular structure, and this energy can be released when an inorganic phosphate (Pi)is removed by hydrolysis to form ADP.  So the next question is: how do cells get a new supply of ATP to fuel their endergonic reactions?

I. Cellular respiration (aerobic respiration) = catabolic metabolic pathway that uses oxygen to release stored energy from carbohydrates, lipids, and proteins.

 A. Energy is released slowly, step-wise, through many enzymatic reactions in the cytoplasm and the mitochondria of the cell.  The released energy is ultimately used to add Pi to ADP to regenerate ATP.
  1. ATP and ADP are constantly cycled.  Energy is added to ADP with Pi to form energy-rich ATP; energy is released when Pi is removed from ATP to re-form ADP.
   a. estimate that single working muscle cell recycles ATP at rate of 10 million molecules per second.

    B. Energy stored in most organic compounds in the potential energy of electrons.
 
        1. Energy is transferred from one molecule to another via the
        transfer of these electrons in redox reactions.
 

        2. Redox reactions (oxidation-reduction reactions) involve two molecules,
        one of which, the reducing agent, donates one or more electrons to the other,
        the oxidizing agent.

            a. reduction =  gain of electrons

            b. oxidation = loss of electrons

        3. Reduced molecules are energy-rich; they give up their energy as they are oxidized.

        4. Hydrogen ions are often transferred along with electrons to keep charges neutral.

            a. AH + B --> A + BH
              AH is reducing agent; it becomes oxidized during redox reaction.
              B is oxidizing agent; it becomes reduced during reaction.
              AH loses energy; B gains energy as it becomes BH.

    C. During cellular respiration, reduced organic molecules are slowly oxidized
    to release their stored energy.

        1. Electrons are systematically removed from organic fuel molecules and
            shuttled to O₂, the ultimate oxidizing agent in the process.

        2. This process is accomplished by a set of metabolic pathways, so all
            reactions are catalyzed and regulated by enzymes.

        3. Electrons (along with H⁺) are usually passed to the coenzyme NAD⁺,
            which carries them to an electron transport chain, where their energy
            can be captured to make ATP.

                a. NAD⁺ = nicotinamide adenine dinucleotide [Fig. 7.3]
                b. NAD+ + 2e- + H+ <--> NADH
               c. NAD+ is most common electron acceptor in respiration,
                but there are others, such as FAD, in the cell.
               d. NAD+ must be regenerated from NADH to keep respiration going.

II. Respiration = mobilization of reduced organic molecules and their
controlled oxidation to release energy for the growth and maintenance of the organism.

    A. Substrates = reduced carbon-based molecules

  1. Carbohydrates
   a. sugars:
   i) small, soluble in water
   ii) intermediate energy storage molecules that can be mobilized quickly.
   e.g., sucrose, glucose, fructose

   b. starch (plants), glycogen (animals):
   i) large, soluble in water
   ii) long-term energy storage molecules made by linking thousands of glucose molecules together into highly branched structures.

  2. Lipids
   a. triglycerides: oils (plants), fats (animals):
   i) glycerol + 3 fatty acids
    ii) insoluble in water
   iii) more reduced than carbohydrates, so have more energy per weight

  3. Proteins
   a. polymers of amino acids
   i) not normally used for energy storage, but do yield energy when they are catabolized
   ii) amino acids are catabolized; excess N waste product from animals goes into urea, excreted in urine.
 

III. Pathways of Aerobic Respiration [Fig. 7.5]
(Aerobic respiration requires O₂; produces maximal amount of ATP per substrate.
Lack of O₂ leads to anaerobic respiration = fermentation.)

    A. Glycolysis = oxidative catabolism of glucose (or other sugar) to yield two molecules of pyruvate, a 3-carbon molecule, plus two ATP and two NADH. [Fig. 9.8]
 Glucose --> 2 pyruvate + 2 ATP + 2 NADH

  1. occurs in cytoplasm of cells
  2. believed to be most ancient respiratory pathway (first evolved)
  3. as glucose is broken down, some energy is captured by substrate-level phosphorylation (= direct formation of ATP), some energy is captured by the reduction of NAD+, but most of the energy is still in the end product, pyruvate.
  4. can occur either in the presence or absence of O2;
   a. if O2 is present, pyruvate goes into Krebs Cycle, and NADH goes to electron transport chain.
   b. if O2 is absent, pyruvate is fermented, which regenerates NAD+ from NADH.
 

        The pathway:

    B. Krebs Cycle = Citric Acid Cycle =  complete oxidative catabolism of pyruvate to CO2, NADH, FADH2, and ATP.
 Substrates enter the Krebs cycle as 2-carbon molecules called acetate, carried by coenzyme A (CoA).
 Pyruvate --> acetyl-CoA + CO2 + NADH

 Acetyl-CoA --> CoA + 2 CO2 + 3 NADH + FADH2 + ATP

      1. occurs in mitochondrial matrix of all eukaryotic cells
           a. mitochondrion = organelle composed of:
                i) smooth outer membrane
                ii) folded inner membrane (cristae)
                iii) matrix = gel-like inner compartment
      2. acetate is added to pre-existing 4-carbon molecule (oxaloacetate) to form a 6-carbon molecule, citrate.  This citrate undergoes several reactions to release 2 CO2 and regenerate oxaloacetate.  During this process, the energy in the acetate is harnessed by substrate-level phosphorylation to form an ATP and by using its electrons to reduce 3 NAD+ and 1 FAD. ]
      3. NADH and FADH2 carry electrons to the electron transport chain, where their energy is harnessed to make ATP.
      4. requires O2 to regenerate NAD+ and FAD (because electron transport chain requires O2).

       5. The pathway:

        6. The process:

 C. Electron Transport Chain = sequence of electron carriers that uses the energy of the electrons brought by NADH and FADH2 to make ATP.
 Oxidative phosphorylation = using controlled redox reactions to phosphorylate (add Pi to) ADP to form ATP.
 2NADH + 6ADP + 6Pi + O2 --> 2NAD+ + 6ATP + H2O
 2FADH2 + 6ADP + 6Pi + O2 --> 2FAD + 6ATP + H2O
(*numbers are approximate, but close)

  1. occurs in inner mitochondrial membrane (cristae)
  2. O2 requiring step of respiration
  3. O2 is reduced by electrons to form H2O
  4. uses chemiosmosis to couple electron transport to ATP synthesis.
   a. Chemiosmosis = potential energy stored in a concentration gradient can be used to do work as substances diffuse down their gradient.  In the case of respiration, the gradient is a proton (H+) gradient.
  5. Electrons are passed along a series of proteins in the membrane.  As the electrons move through, their energy is captured and used to pump protons (H+) across the membrane from the matrix to the intermembrane space.  This creates a proton gradient across the membrane that is effectively like a battery.  The energy of the electrons now is stored in the potential energy of the gradient.  The electrons, at low energy after passing through the e.t.c., are used to reduce O2.  The protons can diffuse back into the matrix by passing through a protein complex called the coupling factor.
  6. ATP synthase = coupling factor = proteins in inner mitochondrial membrane that couple the energy released by proton diffusion to ATP synthesis.

IV. Fermentation = anaerobic respiration

 A. In the absence of O2, the electron transport chain cannot function, so no NAD+ can be regenerated from NADH in the mitochondria.  The Krebs cycle stops.  Only glycolysis can continue to function because fermentation can regenerate NAD+ in the cytoplasm.
  1. Glycolysis makes some ATP by substrate-level phosphorylation, so cells can survive (somewhat).
   a. not nearly as energy efficient as aerobic respiration.
 B. Types of anaerobes:
  1. Obligate anaerobes = some prokaryotes do not possess the enzymes for the aerobic pathways (Krebs cycle and e.t.c.), so they can only perform fermentation.
  2. Facultative anaerobes = other organisms and tissues can survive in the absence of O2, but can also perform aerobic respiration if O2 is present.
 C. Pathways:
  1. lactic acid fermentation = pyruvate acts as the oxidizing agent to regenerate NAD+.
 Glucose --> 2 pyruvate + 2 NADH + 2 ATP
 Pyruvate + NADH --> lactic acid + NAD+

  2. alcohol fermentation = pyruvate is decarboxylated to form acetaldehyde, which is then reduced by NADH to form ethanol.
 Glucose --> 2 pyruvate + 2 NADH + 2 ATP
 pyruvate --> acetaldehyde + CO2
 Acetaldehyde + NADH --> ethanol + NAD+

V. Metabolic connections

    A. Glycolysis and Krebs cycle are not the only catabolic pathways in the cell.  They
    are central in the metabolism of most cells and connect to many other pathways. [Fig. 9.19]

        1. Lipid catabolism
            a. lipids broken down by process called ß-oxidation
                i) feeds glycerol into glycolysis
                ii) fatty acids are broken into 2-carbon acetate units that enter Krebs cycle.

        2. Protein catabolism
            a. amino acids can be catabolized to form pyruvate, acetate, or other
                metabolites that enter Krebs cycle.
            b. excess nitrogen is excreted as urea by animals.

        3. Metabolites can also be taken from glycolysis and Krebs cycle and used
            for synthesis of other compounds in the cell, such as amino acids.

VI. Regulation of Respiration

    A. Enzymes that catalyze reactions control the rate at which substrates are broken down.

        1. Allosteric enzymes at rate-limiting steps are the key regulatory spots.
   a. Glycolysis -- Phosphofructokinase, enzyme in middle of pathway, is most important regulatory site.
    i) ATP is an allosteric inhibitor
    ii) ADP is an allosteric activator
    iii) citrate (from Krebs cycle) inhibits

   b. Makes sense because overall goal of respiration is to produce ATP, so if cell has enough, the pathway slows down.  If cell doesn't have enough ATP, it has a lot of ADP, so this speeds up respiration.
   c. ATP and citrate regulation of phosphofructokinase is an example of feedback inhibition.

   d. Other allosteric enzymes help regulate glycolysis and Krebs cycle, too.
 

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