Respiration

Main Points:

  1. Cells harvest the potential energy stored in chemical bonds. Ultimately this is the same energy that arrived to the surface of the as kinetic energy in form of solar radiation and was converted to chemical energy through the process of photosynthesis.
  2. Cellular Respiration oxidizes organic molecules and has three steps: Glycolsis, the TCA cycle and electron transport.
  3. The catabolism of proteins and fats can release a large amount of energy
  4. Cells can metabolize food without oxygen, but the process is much less efficient than aerobic respiration.

I. Cells Harvest the Potential Energy Stored in Chemical Bonds

Only plants, algae and some types of bacteria can harvest the energy of sunlight directly (most prominently via Photosysnthesis). For the remaining 95% of the diversity of life on earth, gaining energy requires harvesting the energy the autotrophs store in the chemical bonds of organic molecules such as glucose and other carbohydrates, proteins and fats.

Digestion - large molecules enzymatically are broken down into smaller ones

Catabolism - continues the process, harvesting energy

As we will see, many organic molecules can be used to drive cellular metabolism, but for simplicity we will consider glucose (C6H12O6) to be the substrate for respiration.

The overall equation is simply the reverse of the one we used for photosynthesis

C6H12O6 + 6O2 --> 6CO2 + 6H2O + energy

The energy released from the covalent bonds is ultimately converted to ATP or lost as heat. Electrons also become available as the bonds are broken and can be donated to molecules via Redox reactions. When electrons (and an associated H+) are transfered to oxygen, a molecule of water is formed. Obviously this form of respiration requires oxygen and simply can not be accomplished without it and thus is known as Aerobic Respiration. Anaerobic Respiration is the alternative (and older) form of catabolism and results in the reduction of an inorgainc moleulce other than oxygen.

Cellular Respiration is a very similar process to buring wood. The required componets are carbohydrates and oxygen and the products are carbon dioxide, water and energy.

Within a cell the change in Free Energy betwen the reactants and the products of respiration (the complete oxidation of glucose) is -720 kcal mol-1. This energy is primarily harvested by breaking the six C-H contained within a glucose molecule. In order for this energy to be usefule (not lost as an increase in entropy) cells convert this energy to ATP.


Figure 9.3 from your text

Within cells ATP is used as an energy source for movement and to drive endergonic reactions (energy requiring).

Enzymes that complete endergonic reactions have two binding sites - one is the active site for the reactant to bind to the enzyme the other for ATP. As the reaction proceeds an inorgainc phosphate molecule (Pi) is cleaved from the ATP by the ezyme, liberating the energy (>7kcal mol-1) stored in the bonds between the negatively charged phosphate groups.


Figure 9.4 from your text

II. Cellular Respiration Oxidizes Organic Molecules And Makes ATP

Cells are able to make ATP during the catabolism of organic moleculesin two different ways.

  1. Substrate-level phosphorylation: ATP formation by the the direct transfer of a Pi to ADP from phosphate containing intermediates.


    Figure 9.5 from your text?

  2. Aerobic Respiration: via redox reactions using an electron transport chain and ultimate oxygen as an electron acceptor.

Overview of Glucose Catabolism


Figure 9.6 from your text

  1. Glycolysis
    • 10 reaction biochemical pathway which produces ATP via substrate-level phosphorylation
    • Enzymes are found in the cytoplasm and are not membrane bound
    • requires 2 ATP to drive and produces 4 ATP (a net gain of 2 mol ATP mol of Glucose)
    • 4 electrons are transfered to NAD+ and can be used to form ATP in aerobic respiration (if oxygen is present)
  2. Aerobic Respiration
  3. Anaerobic Respiration
    • In the absence of oxygen, some organisms respire anerobically, using different inorganic electron acceptors in place of oxygen
      • Methanogens - primative archaebacteria such as thermophiles can use CO2 as the ultimate electron acceptor producing methane (CH4)
      • Sulfur Bacteria - also present in primitive bacteria, sulfate reduction to H2S can provide energy for cellular metabolism

There are 3 component processes of Aerobic Respiration:

  1. Glycolysis
    • carried out in the cytoplasm of a cell (not membrane bound, not associated with a specific organelle)
    • can work in the absence of O2 (uses no oxygen)
    • oxidizes glucose to pyruvate
      • Priming
        • 5 reactions convert glucose to glyceraldehyde 3-phospate (G3P)
        • Demand the input of ATP to break the covalent bonds of the glucose molecule
          • The first three reactions rearrange the molecule (Priming), requiring 2 ATP
          • Two reactions cleave the six-C product into 2 molecules of G3P (ultimately)
      • Substrate-Level Phosphorylation
        • 5 reactions convert G3P into pyruvate
          • Two electrons and a proton are transfered from G3P to NAD+
          • Four reactions convert G3P into pyruvate
          • generates 2 ATP and two NADH
    • 3.5% energy capture
      • Each ATP represents 12 kcal mol-1 (under cellular condidtions)
      • Total energy harvest from glycolysis of 24 kcal mol-1
      • Total energy available in glucose is 686 kcal mol-1
    • thought to be among the earliest of all biochemical processes to evolve
    • used by all cells
    • can be followed by one of two processes:
      1. Fermentation
      2. Oxidative respiration

    Figure 9.7 from your textbook

    As Glycolysis continues the cellular concentration of NADH is increased and the concentration of NAD+ is depleted. Since the cellular pool of NAD+ is quite limited the NADH must be recycled into NAD+ for the glycolytic reactions to continue. A secondary electron acceptor is needed to re-oxidize NADH. Two pathways are available for this purpose:

    1. Fermentation
      • anaerobic
      • can recycle NADH back to NAD+ (in order to allow glycolysis to continue)
      • common in bacteria
        • can produce organic acids
          • acetic acid
          • butyric acid
          • propionic acid
          • lactic acid
      • Yeast
        • produce ethanol (decarboxylation of pyruvate forms CO2 and makes your bread rise or your beer carbonated!)
      • Multicellular animals
        • produces lactic acid
    2. Aerobic respiration
      • O2 is an excellent electron acceptor and forms water in respiration
      • uses the Citric Acid or Krebs cycle
      • takes place in mitochondria
      • aerobic
      • extracts a large amount of energy
        • 2 ATP directly
        • The rest of the electrons removed from glucose bonds are transported to the mitochondrial electron transport chain as NADH or FADH2
        • cyclic - regenerative like the Calvin cycle of the dark reactions of photosynthesis

      Figure 9.8 from your textbook

    3. The Oxidation of Pyruvate

      In the presence of oxygen the continuation of the oxidation of glucose takes place inside the mtiochondion

      Figure 5.23 from your textbook

      Pyruvate is converted to Acetyl Coenzyme A

      • decarboxylation (gives off CO2) and leaves an acetyl group
      • redox (transfers electrons and a proton to NAD+)
      • complex mulenzyme process (pyruvate dehydrogenase multienzyme complex)
      • combines with a coenzyme (CoA)
      • acetyl-CoA a commonly used molecule in cellular metabolism and is a key to energy storage (fatty acid sysnthesis)
      • acetyl-CoA is further oxidized by the Krebs cycle

        Figure 9.10 from your textbook

  2. The Krebs Cycle
  3. Acetyl-CoA is oxidized in a series of nine reactions called the Krebs Cycle, after its founder Sir Hans Krebs. This cycle is also known as the Tri Carboxylic Acid cycle (TCA) and the Citric Acid Cycle.

    Krebs won the 1953 Nobel Prize in Medicine for his discovery of the citric acid cycle

    1900-1981
    Place of Birth: Hildesheim, Germany
    Residence: Great Britain
    Affiliation: Sheffield University

     

    The reactions of the Krebs cycle are completed within the mitochndrial matrix

    • the two-carbon acetyl group combines with a four-carbon oxaloacetate.
    • the resulting six-carbon compound is oxidized yielding electrons that are transfered to NAD+ and FAD+
    • two CO2 molecules are split off and the original four-carbon oxaloacetate is reformed
    • the reductant formed is used to generate a proton gradient to drive the fromation of ATP

    The Nine reactions can be divided into two steps:

    1. Priming - 3 reactions form citrate and prepare it for energy extration
      • Condensation - Citrate formation from Acetyl-CoA and Oxaloacetate
      • Isomerizaton - repositioning of the hydroxyl goup to form isocitrate (two steps)
    2. Energy Extraction - six reactions, four of which are oxidations (giving up electrons) and a fith generates ATP directly via substrate-level phosphorylation
      • Oxidative Decarboxylation of isocitrate to alpa-ketoglutarate
        • yields a CO2 and reduces NAD+
      • Oxidative Decarboxylation of alpa-ketoglutarate to Succinyl-CoA.
        • yields CO2 and reduces NAD+
        • requires the input of CoA
      • Substrate-Level Phosphorylation
        • guanosine diphosphate (GDP) is used as an intermediate
        • forms guaosine triphosphate (GTP)
        • GTP is converted into ATP
        • CoA is relased
        • the four-carbon succinate remains in the cycle
      • Oxidation of succinate to fumarate
        • reduces FAD+ (flavin adenine dinucleotide) - energy not sufficinet to reduce NAD+
        • FADH2 remains within the inner mitochondria lmembrane
      • Regeneration of Oxaloacetate
        • Fumarate is hydrated
        • Malate is oxidized
        • Oxaloacetate is formed
        • NAD+ is reduced

    Figure 9.11 from your textbook

    In Areobic Respirtion, glucose is entirely consumed

    • Glucose cleaved in two two 3 carbon Pyruvate molecules
    • One carbon from each of the two pyruvate molecules is lost during the conversion to Acetyl-CoA
    • Two more carbons are lost per pyruvate in the Krebs cycle
    • 4 ATP molecules are formed
    • 10 NADH are formed
    • 2 FADH2 are formed

    4. Harvesting Energy By Extracting Electrons

    Figure 9.12 from your textbook

    In respiration, the energy contained in the covalent bonds holding glucose together is transfered in a series of steps as the electrons are shifted to form water, from oxygen, a more electronegative compound. By transferring the energy in smaller steps less is lost to entropy and more energy remains in the useful form. (similar to buring a tank of gas a spoonful at a time instead of exploding the entire tank at once.

    Enzymes always extract two electrons and two protons. Then these electrons and one of the H+ ions is transfered to a coenzyme carrier - NAD+. The other proton is released into the surrounding fluid. The transfer of electrons from NADH to oxygen happens in many smaller steps, regulated by the electron transport chain embedded within the inner membranes of the mitochondria. In total 53 kcal mol is released and gradually the energy is extracted.

    5. The Mitochondrial Electron Transport Chain

    The NADHand FADH2 formed in the earlier parts of respiration are transfered to the inner mitochondrial membrane, where a group of membrane bound proteins are used to transport electrons away from these combounds to oxygen.

    Figure 9.15 from your textbook

    The energy harvested from the breakdown of glucose and transferred to NAD+ eventually enters the mitochondrial electron transport chain where it is passed from protein to protein. upiquinone (Q) and cytochrome c (C) are mobile in the membrane lipid bilayer and shuttle the energy between the proteins. It takes four electrons to reduce one molecule of oxygen to water. Three of the five most common proteins involved in this process use part of the electrons energy to transport protons out of the matrix and into the intermembrane space.

    The final electron acceptor is oxygen and the final enzyme complex is the largest of the membrane bound proteins, composed of 11 subuints that form a channel through the membrane for proteins and electrons.

    Figure 9.14 from your textbook

    Since 3 of the 5 proteins in the chain exclude protons and 2 protons are consumed in the reduction of oxygen, a strong electrical gradient is built up between the mitochondrial matrix (proton poor) and intermembrane space (becomes proton rich). The negative charge within the matrix attracts the positively charged protons which must re-enter the matrix via a proton channel in the membrane leading to the formation of ATP.

    Figure 9.16 from your textbook

    Chemiosmosis - the formation of ATP driven by the diffusion of protons from the intermembrane space into the mitochondrial matirx through specialized channels.

     

    Summary of ATP generation, begining with pyruvate and ending with ATP

    Figure 9.17 from your textbook

Summary of Aerobic Respsiration

Theoretical Yield:

From Figure 9.18 of your textbook

Actual Yield:

At 12 kcal mol-1 of ATP, thats 360 kcals per glucose (12 * 30)

Glucose contains 686 kcals so the actual harvest of energy is about 52%, not bad considering the typical car harvest only about 25% of the energy in gasoline!

Regulating Aerobic Respiration

  1. ATP/ADP
    • activation
    • deactivation
    • feedback regulation
  2. Phosphofructokinase
  3. Citrate
    • indicative of Krebs cycle activity
    • deactivation
  4. NADH

Figure 9.19 from your textbook

 

C. Catabolims of proteins and fats can yield considerable energy

Organic molecules other than glucose are important sources of cellular energy

Proteins are first broken down into amino acids via deamination

the remaining carbon can enter glycolysis or the Krebs cycle

Fats are broken down into fatty acids plus glycerol.

many -CH2 links rich in energy

2 carbon acetyl groups are cleaved one at a time to form Acetyl-CoA via beta-oxidation.

Yield

6 carbon fatty acid via beta-oxidation (twice)

  • 2 rounds of beta-oxidation = 3 molecules Acetyl-CoA (=10 ATP per Acetyl-CoA = 30 ATP total)
  • 1 ATP per round to prime (-2 ATP)
  • 1 NADH per round (=2.5 ATP * 2 = 5)
  • 1 FADH2 per round (=1.5 ATP * 2 = 3)
  • Total = 30 - 2 + 5 + 3 = 36 mol ATP per mol glucose

compares to 30 mol ATP per glucose!

Fatty Acids yeild 20% more energy

And fatty acids weigh about 2/3 as much as glucose, so a gram of fatty acid contains more than twice as many kcals and a gram of glucose! No wonder animals store energy as fat!

Figure 9.20 from your textbook

 

D. Cells can metabolize food without oxygen

Without oxygen areobic metabolims can occur and cells must rely exclusively on glycolysis for ATP production.

Leads to the reduction of organic molecules bia fermentation.

more than a dozen types (each using an orgainc molecule to accept the electrons from NADH and regenerate NAD+)

often produces organic acids or alcohols

  • acetic acid
  • butyric acid
  • propionic acid
  • lactic acid
  • ethanol

Ethanol Fermentation

carried out by single celled fungi called yeast and begins with pyruvate

pyruvate is decarboxylated giving off CO2 and forming acetaldehyde

(guess what this does for your bread or your beer!)

acetaldehyde accepts a hydrogen from NADH and regenerates NAD+

Ethanol is is the final product!

as a byproduct of the reaction, ethanol is actually toxic to the yeast and as the concentration approaches 12% the yeast begins to die. What is the alcohol content of a dry wine?

 

Lactic Acid Fermentation

In animal cells the regeneration of NAD+ can proceed without a decarboxylation reaction

pyruvate can be converted into lactic acid

Anerobic excercise leads to the production of lactic acid and if this acid is not removed by the circulatory system it will lead to muscle fatigue.

Figure 9.21 from your book

 

 


Useful Links

MIT's Biology Hypertextbook

Online Biology Book from MaricopaCommunity College

U of A Metoblism Problem Set

Rice University

Lecture by Professor Kevin Griffin.

Updated April 19, 2005
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