Topic 8.1 : Cellular Respiration

Cellular Respiration - controlled release of energy from organic compounds in cells to form ATP
          -Occurs in both plants and animals

2 Pathways of Cellular Respiration:

      

- Both begin with glycolysis

        

        a.) Anaerobic Respiration

            

                 - Oxygen = not available

                       

                        1.) Alcoholic Fermentation - Yeast

                       

                        2.) Lactic Acid Fermentation - Muscles

       

        b.) Aerobic Respiration

                

                 - Most efficient pathway

                 - Oxygen = available

                

                 - Yields large amounts of ATP

                 - Occurs in mitochondria

Glycolysis                                                                                

 -Takes place in cytosol                                            

     - First pathway of cellular respiration

     - Begins with glucose

   

Lactic Acid and Alcoholic Fermentation

Lactic Acid Fermentation

          - Muscle cells, yogurt cheese

          - Produces NAD+ and lactic acid

Alcoholic Fermentation

        - Yeast

        - Produces NAD+ and ethyl alcohol

Aerobic Cellular Respiration

   a.) Glycolysis in cytoplasm

   b.) Krebs Cycle and ETC in Mitochondria

   

2 Types of Chemical Reactions:

    a.) Oxidation 

      - Results in many C-O bonds

      - Results in compounds with lower potential energy

    b.) Reduction

      - Results in many C-H bonds

      - Results in compounds with higher potential energy

          

  

Fe2+à Fe3+ + electron       Oxidation

Fe3+ + electron à Fe2+        Reduction    

Terms:

   -Phosphorylation: addition of phosphate group to compound/molecule

        Ex: Glucose + 2 ATP --> Hexose Bi-phosphate

   - Substrate-Level Phosphorylation: way of producing ATP

        Ex: ADP + Phosphate --> ATP

   - Decarboxylation: removal of carbon atom

   - Oxidative Decarboxylation: removal of hydrogen atom and carbon dioxide

   - Coenzyme: molecule that aids an enzyme in its action by acting as electron donor/acceptor

       Ex: Acetyl CoA

Uses for ATP in Respiration

     a.) Releasing energy

           - Breaking of chemical bonds

           - Loses phosphate

                  - Bond between 2nd and 3rd phosphate group broken

      b.) Substrate Level Phosphorylation

              - Forming ATP

                  - Cells create ATP to store energy

                  - ADP--> grabs Pi --> Energy stored in ATP bond

                  - Breaking down ATP to make ADP to release energy

Glycolysis

     - Splitting of glucose into two pyruvate (3-carbon molecules)

     - One hexose sugar converted into two 3-C atom compounds (pyruvate) with net gain of 2 ATP and 2 NADH + H+

               - Both pathways begin with:

                         - Total of 4 ATP molecules

                         - Requires 2 ATP to start process -- net gain of 2 ATP per glucose molecule

4 Steps to Glycolysis:

Step 1 - Phosphorylation - Energy Investment Phase

      - Phosphates from 2 ATPs are added to glucose to create hexose bi-phosphate molecule

    1.) Hexokinase (enzyme that transfers 1st phosphate to sugar)

         - Product formed called Fructose-6-Phosphate

    2.) Phosphofructokinase (2nd enzyme that transfers 2nd phosphate to sugar) -

         - Product formed called Fructose-1, 6-bi-phosphate (hexose bi-phosphate) 

                -- 6 carbon sugar with 2 phosphates attached

Step 2 - Lysis

      1.) 6-carbon phosphorylated fructose splits by enzyme aldolase into two, 3-carbon sugars with       phosphate attached

          -Product formed: 3-carbon sugars (G3P) - triose phosphate molecules

Step 3 - Oxidation - Energy Payoff Phases begin

      1.) Each G3P undergoes oxidation by enzyme triose phosphate dehydrogenase where it loses 2 atoms of hydrogen by reducing NAD+ into NADH + H+

        2.) While NADH is formed, releases energy enzyme then uses to add phosphate group to both of 3-carbon molecules with one phosphate group

          - Results in a 3-carbon molecule with 2 phosphate groups attached (Phosphogylcerate - PGA)

Step 4 - ATP Formation

      1.) Enzyme removes the 2 phosphate groups

      2.) Enzyme Enolase extracts water molecule, forming phosphoenolpyruvate (PEP)

      3.) Phosphate groups transferred from PEP to ADP (substrate-level phosphorylation_)

      4.) ATP is produced

           - Product: 2, 3-carbon molecules called Pyruvate

Glycolysis Summary

     - 2 ATPs used to start process

     - 4 ATP produced (net gain of 2)

     - 2 NADH molecules produced (NAD+ converted into NADH + H+

     - Includes: phosphorylation, lysis, oxidation, ATP formation

     - Pathway controlled by enzymes

     - In cytoplasm, one glucose (6C) is converted into 2 pyruvate (3C) molecules

Mitochondrial Structure in Relation to its Functions

1. Cristae folds increase surface area for electron transfer system

2. Double membrane creates small space into which H+ can be concentrated

3. Matrix creates isolated space in which Krebs cycle can occur

 

Aerobic Cellular Respiration

1.) Glycolysis (see above)

2.) Link Reaction and Krebs Cycle

     - Occurs in mitochondrial matrix

     - Requires Oxygen

 a.) Link Reaction:

         - Produces 1 CO2 and 1 NADH for every pyruvate

 b.) Krebs Cycle

         - 2 ATP produced for life processes

                 *1 from one Krebs Cycle runs twice

         - 6 Molecules of NADH produced

                 *3 from one Krebs Cycle that runs twice

         - 2 Molecules of FADH2 produced

                 *1 from Krebs Cycle that runs twice

         - 4 Molecules of CO2 produced

                 * 2 from Krebs Cycle that runs twice

3.) Electron Transport Chain

         - Requires oxygen

               a.) Final electron acceptor

         - Where most of ATPs from glucose catabolism produced

         - Occurs in intermembrane space and membranes of cristae

         - Water = waste product

Aerobic Cellular Respiration Step 2 Part A: Link Reaction

   1.) Pyruvate from glycolysis absorbed by mitochondria after glycolysis when oxygen = present

   2.) Pyruvate enters matrix of mitochondria by active transport

   3.) Oxidative decarboxylation

        - Goal = hydrogen and carbon dioxide removed from pyruvate

   4.) Enzymes in matrix of mitochondria remove hydrogen and carbon

   5.) Pyruvate = decarboxylated to form acetyl group (2C)

         - CO2 released

   6.) Pyruvate = oxidized

         - Hydrogen atom accepted by NAD+ to form NADH + H+

     7.) Acetyl group combines with coenzyme (CoA) to form Acetyl CoA

    8.) Acetyl CoA then enters Krebs cycle to continue aerobic respiration process in matrix of mitochondria

Acetyl coenzyme A (Acetyl CoA)

     - Pyruvic Acid from Glycolysis converted to Acetyl CoA - 2C compound

Cellular Respiration using Fatty Acids
    - Fatty acids = source of energy in cellular respiration
CH3(CH2)nCOOH
   ** Glycolysis = not needed; goes straight  to link reaction **
- Fatty acids have long chain of carbon atoms.
- CoA can oxidize this chain and break it down

 - Fatty acids make Acetyl CoA with two carbons and carries them to Krebs Cycle

                      - If odd number of carbons, remaining carbon atom released as CO2

Krebs Cycle

—Acetyl CoA (CH3CO) yields 2 CO2

C2 + C4 = C6 → C5 + CO2 → C4 + CO2

    

Aerobic Cellular Respiration Step 2: Part B: Krebs Cycle
1.) Formation of citrate
      - Acetyl CoA from link reaction combines acetyl group (2C) with oxaloacetate (4C)
           2C + 4C = 6C
      - Results in 6-carbon molecule called citrate/citric acid
2.) Citrate converted to isocitrate by removal of one water molecule and addition of another
3.) Oxidation
      - Isocitrate (6C) goes through oxidative decarboxylation to form a 5C compound (Alpha-ketoglutarate)
             NAD+ is reduced to NADH + H+ (oxidized).
             Carbon dioxide removed decarboxylation process to form waste product
4.) 5C = oxidized and decarboxylated again
      - Coenzyme A added to form 4C compound (succinyl-CoA)
      - CO2 released

      - NAD+ --> NADH + H+ 

      5.) This 4C undergoes various changes to be converted back into oxaloacetate (4C)
            
                   - Phosphate group displaces CoA from succinyl-CoA which produces succinate (4C)
           
          - Substrate-Level Phosphorylation
        
        6.) Succinate is oxidized by molecule FAD (Flavin adenine dinucleotide)
          
              - Creates Fumarate (4C) FAD--->FADH2

        7.) Enzyme adds water to fumarate to form malate (4C)

        8.) Malate oxidized by NAD+ molecule reducing NAD+ to NADH + H+ and regenerating oxaloacetate
             Produces:
              - 2 ATP
              - 6 NADH
              - 2 FADH2
              - Oxaloacetate
              - 4 CO3
        Oxaloacetate will begin cycle again 
             

            

          - Cycle follows one acetyl group
          
          - Each glucose that enters will produce 2 acetyl groups                        

           

      Aerobic Cellular Respiration Step 3- Electron Transport Chain 

      

      - Pathway where most of ATPs from glucose catabolism are produced

     

      - Contains series of electron carriers

                - Carriers will form "chain" to pass electrons and proteins from one another

 -              - As electrons are transported, small amounts energy released

      - NADH and FADH2 from Krebs Cycle will pass electrons to ETC

      

      - Electrons passed as H+ ions to be pumped out of matrix --> cross into inner mitochondrial matrix --> travel into intermembrane space

                   - Proton gradient = produced

                   - Energy = released in process

       ETC Steps

       1.) NADH supplies 2 electrons to first carrier in chain (initially flavoprotein - FMN) and then series of Fe-S proteins

             - Drops off H2 in inner mitochondrial space

             - Turns into NAD+ again

       2.) The 2 electrons pass along chain of carriers because they give up energy each time they pass from one carrier to next

       3.) At 3 points along chain enough energy is given up for ATP to be made by ATP synthase

       4.) Proteins move from inner membrane space to matrix and produce ATP (Oxidative Phosphorylation)  

               - ATP synthase = located in inner mitochondrial membrane         (look on ppt for detailed arrows)

* In the chain, electrons pass from one carrier to another because receiving molecule has a higher electronegativity (stronger attraction of electrons)

- Process accomplishes pumping of four protons across inner mitochondrial membrane to inner membrane    space (used to generate ATPs)

5.) The iron sulfur protein then passes electrons to compound ubiquinone (Q - lipid (only member not a protein)

       - Most of remaining electron carriers between Q and oxygen are proteins - cytochromes (cyt)

       - Cytochromes prosthetic group = heme (iron atom) 

6.) FADH2 enters ETC further along --> sufficient energy released for ATP production by electrons for FADH2

       - FADH2 passes electrons to electron carrier

       - Hydrogen = moved from matrix to intermembrane space

  - Products: Carbon dioxide, water, and ATP

Role of Oxygen

 - Final electron acceptor in ETC

 - Oxygen accepts hydrogen ions to form water

 - If oxygen = not available, electron flow along ETC stops

 - Glycolysis can still occur

Oxidative Phosphorylation in terms of Chemiosmosis
- Process that occurs at inner membrane
- Chemiosmosis involves movement of protons (H2 ions) moving across membrane (down its concentration gradient) to provide energy so that oxidative phosphorylation (ATP synthesis) can occur
    A.) ATP synthase:
          - too many H2 ions are in intermembrane space (high concentration)
          - creates overall positive charge
          - Accumulation of H2 will cause proton force
                    - Allows movement of H2 ions through ATP synthase --> uses energy from H2 flow to couple phosphate with ADP to produce ATP

         - The Production of ATP

               - ATP synthase uses energy from H2 flow to phosphorylate with ADP

                     - ATP = produced

                  * Each NADH pumped 3 pairs of H2 atoms --> produces 3 ATPs

Protons move from inner membrane space to matrix

7.5 Proteins

Four levels of protein structure

1. Primary Structure = amino acid sequences

   a) These are polypeptide chains (between 50-1000 amino acids in length)

   b) 20 amino acids

   c) R groups of amino acids aid in shaping the protein

Primary Structure

   a) The primary structure forms a –N-C-C-N-C-C-N-C-C- backbone to the molecules

   b) The primary structure is read from the NH2 – terminal to the –COOH terminal

   c) Each amino acids is identified by its specific R group

Secondary Structure

1. Secondary Structure = describes the shape of the protein

   a) There are two main types:

      i) Alpha helix

      ii) Beta pleated sheets

   b) Both stabilized by hydrogen bonding between groups in the main chains

   c) The primary structure of a polypeptide has group projecting from the N-C-C backbone

   d) There are three noted forms of secondary structure

Secondary Structure- Alpha Helix

   a) Formed from hydrogen bonds

   b) This is drawn as a helix that follows the –N-C-C-N-C- backbone of a polymer

   c) Alpha helices are often the basis of fibrous polymers (i.e. collagen)

   d) Right handed helix

   e) The alpha helix was first discovered by Linus Pauling

Secondary Structure- Beta-Pleated Sheet

   a) Beta-pleated sheets are so called because of the ‘pleated’ or folds when viewed from the side

   b) The polypeptide chain is much more stretched out in comparison to the alpha helix

   c) This ‘sheet’ often has twists that increase the strength and rigidity of the structure

   d) This beta-pleated sheet was discovered by Pauling and Corey

Structure- Open Loops

   a) Alpha helices and beta-pleated sheets are often connected together by short chains of amino acids which form neither of the previous structures but simply link other sections together

   b) They are in fact often important regions of proteins including the active sites of enzymes

Tertiary Structure

   a) The overall shape of conformation of a polypeptide.  Basically its just referring to the folds in a polypeptide chain

   b) These folds are formed just after translation

   c) Caused by bonding of the R groups together

   d) Hydrophilic R groups bond to each other

   e) Hydrophobic R groups bond to each other

   f) Types of intramolecular bonds may include covalent, ionic, hydrogen, disulphide bridges, and hydrophobic interactions

Tertiary Structure- Disulphide Bridges

   a) R groups that have sulfer will form covalent bonds between one another (i.e. between two adjacent cysteine amino acids).  This forms a disulphide bridge.

   b) The covalent bond stabilizes the tertiary shape of a protein

 

Quaternary Structure

   a) A number of tertiary polypeptides joined together

   b) Hemoglobin is a quaternary structure

   c) It is composed of 4 different polypeptide chains

   d) Each chain forms a tertiary structure called a hem (haem) group

   e) Prosthetic groups: proteins are often bond to inorganic groups (e.g. Hemoglobin has four polypeptide ‘hem’ groups each associated with Fe2+.)

Fibrous Proteins

   a) Are water insoluble, long and narrow proteins

   b) Are associated with providing strength and support to tissue

   c) Collagen is the basis of the connective tissue and is composed of three left handed helices.  They make up the extracellular matrix and are found in cartilage, ligiments, tendons, etc.

   d) This is the most common protein in animals

   e) Keratin is another common fibrous protein which is composed of seven helices (major protein in hair and nail structure)

Globular Protein

   a) Are near soluble (colloids)

   b) They have more compact and rounded shape

   c) Are associated with functions such as: pigments and transport proteins (hemoglobin, myoglobin, lipoproteins)

   d) Immune system (immunoglobins)

   e) Structural motifs- sophisticated method of describing protein structure

   f) Examples are enzymes, hormones, hemoglobin and immunoglobin (antibodies)

Significance of Polar and Non-Polar amino acids

   a) Polarity of amino acids depends on the R groups

   b) Polar amino acids have hydrophilic R groups

   c) Non-Polar amino acids have hydrophobic R groups

Polar A.A.

   a) Water soluble

   b) In the cell membrane:

      i) They create channels in proteins for hydrophobic substances to pass through

      ii) They cause part on the membrane proteins to protrude from the cell membrane

      iii) Transmembrane proteins have two polar regions (one on surface and one in channel)

   c) Cell membrane proteins:

      i) The sections of the molecule that contain polar amino acids are hydrophilic and can exist in contact with water.

      ii) Polar amino acids allow the positioning proteins on the external and internal surface of a cell membrane.  Both cytoplasm and tissue fluid are water based regions.

Non-Polar A.A.

   a) Water insoluble

   b) They stabilize the entire protein when found in the center of the water soluble amino acids

   c) They cause proteins to remain embedded in the cell membrane

Polar v. Non-Polar

   a) The lining of the channel itself will be of polar amino acids to allow the diffusion of charged molecules and ions

   b) Polar amino acids within the active site of an enzyme allow a chemical interaction between the substrate and the enzyme to form an activated complex

Four Functions of Protein:

1. Hormones (globular)-

   a) Insulin is a hormone that reduces blood sugar

   b) Produced in the beta- cells of the pancreas islets

   c) Main target tissue is muscle cells and liver cells

   d) Function: to bring about the update of glucose across the cell membrane and the storage of glucose as the insoluble polymers glycogen

2. Immunoglobulins (globular):

   a) Known as antibodies

   b) Produced by the plasma cells in an immune response to an infectious antigen

   c) Great variation exists in the heavy chains which allows a response to virtually any possible antigen surface

3. Enzymes (globular):

   a) Enzymes reduce the energy of activation and allows biochemical reaction to reach equilibrium more quickly

   b) Enzymes are large globular proteins often with prosthetic groups

   c) The maximum number of substrate molecules that can be converted into product per second (excess substrate) is called the ‘turn-over rate’

4. Gas Transport (globular):

   a) Hemoglobin molecules aid in binding oxygen to red blood cells then transporting it to respiring tissues

   b) They are contained within the erythrocytes (red cells) of the circulatory system

   c) Composed of 4 hem groups each associated with a prosthetic Fe2+ ion

   d) Each hem group can carry an oxygen atom

Proteins contd.

   a) Collagen (fibrous): provides structure for the skin

   b) Actin and Myosin (fibrous): aids muscle contraction

   c) Fibrin (fibrous): aids in the clotting of blood