Topic 11: Cellular Respiration

Cell respiration is catabolic.  This means organic compounds are broken down into smaller molecules (like CO2 and H2O) and energy is released
- carbohydrates (mainly glucose) and fats are the main sources of energy
- proteins are rarely used for energy - they are important as building blocks for growth and repair - they will only be converted to carbohydrates and used for energy if there are no carbohydrates available.

2 types of respiration:
1. Aerobic:  called biological oxidation, it needs O2
-in simplified version: C6H12O6 and 6 O2 react in the presence of enzymes to produced 6 H2O, 6 COand energy.
2.  Anaerobic:  called fermentation, it doesn't need O2, the overall process is simpler and faster than biological oxidation, but produces much less energy.

GLYCOLYSIS
- this is the 1st step of both aerobic and anaerobic respiration
-it occurs in the cell cytosol
-it doesn't need O2, but it does require energy (2 ATP)

 Image from http://www.factmonster.com/images/cig/biology/03fig02.png
Step 1.  Energy is required to begin the process, so a molecule of glucose accepts two high-energy phosphate groups from two ATP molecules.

Step 2. The resulting intermediary molecule immediately divides into two, three-carbon molecules called PGAL, each containing a high-energy phosphate group.

Step 3.  A second high-energy phosphate group is added to the three-carbon PGAL molecule and two NADH + H+ molecules are produced.

Step 4.  Finally, the three-carbon PGAL molecules donate their high-energy phosphate to create ATP and the three-carbon pyruvate forms as the final products.

- 4 ATP molecules are produced in glycolysis, but since 2 are required to start the process, the net gain is 2 ATP.  This is not sufficient energy to maintain complex life systems, so pyruvate (also called pyruvic acid) (which still contains energy) will continue into biological oxidation or fermentation, depending on the availability of O2

-if O2 is present, then pyruvate enters the mitochondria:
 
AEROBIC RESPIRATION
- has 2 parts:  biological oxidation and terminal oxidation
- requires O2
- occurs in the mitochondria


Image from http://imagineannie.files.wordpress.com/2009/11/mitochondria1.jpg


Biological oxidation
-the first reaction occurs in the outer membrane of the mitochondria:
pyruvate (CH3COCOOH) reacts with CoA (coenzyme A)to form acetyl-CoA (CH2CO-CoA) by losing a carbon as CO2.

-acetyl-CoA will enter the Kreb's Citric Acid Cycle in the mitochondrial matrix


Note: Acetyl-CoA is a 2-carbon compound, citric acid is a 6-carbon compound and oxaloacetic acid is a 4-carbon compound.  When CoA is released it will return to the membrane to produce more acetyl-CoA.
Image from http://www.factmonster.com/images/cig/biology/03fig03.png

- the image above is a summary of nine enzyme-controlled reactions.

Step 1. Acetyl-CoA donates the two-carbon acetyl group to a four-carbon intermediary compound, oxaloacetic acid, to create the six-carbon citric acid molecule.

Step 2. The high-energy electrons are oxidized to create the energy-rich NADH + H+ molecule when the six-carbon compound loses a carbon dioxide molecule to become a five-carbon molecule.

Step 3. A second molecule of NADH + H+ and a molecule of ATP are produced when another carbon dioxide molecule is released from the five-carbon molecule, which then degrades to a new four-carbon molecule.

Step 4. The four-carbon molecule is further oxidized to transfer high-energy electrons to create the high-energy compound, FADH2, and more NADH + H+.

Step 5. Enzymes rearrange bonding within the four-carbon molecule to become oxaloacetic acid, which combines with the acetyl-CoA to restart the Kreb's cycle.

Summary:  The Kreb's Cycle produces 10 ATP and molecules of FADH2 and NADH + H+, which will be used in terminal oxidation.  The CO2 is a waste product and will be expelled.



-Szent-Györgyi Albert won a Nobel Prize in 1937 for his discoveries in connection with biological oxidation

Terminal Oxidation 
-it occurs on the cristae (inner membrane) of the mitochondria
-it is an electron transport chain, made up of a series of coupled oxidation-reduction reactions
-each of the reactions releases energy, which is eventually used to form ATP from ADP and P.  


Image from http://www.molvray.com/sf/exobio/images/electron_chain.jpg

Step 1:  High energy electrons from NADH + H+ and FADH2 enter the electron transport chain and are passed from molecule to molecule, losing energy in a controlled stepwise manner.

Step 2:  The energy lost from the electrons is used to pump hydrogen ions from the inner mitochondrial compartment to the outer mitochondrial compartment across the mitochondrial membrane. This creates an area of high hydrogen ion concentration on one side of the mitochondrial membrane and a low hydrogen ion concentration on the other side of the membrane. The result is a concentration gradient across the inner membrane creating a source of potential energy, which is again comparable to the potential energy of water held back by a giant dam.

Step 3:  The concentration gradient is used as a source of potential energy to drive the chemiosmotic synthesis of ATP.

Step 4:  A carrier protein helps the hydrogen ions diffuse through a channel protein opening in the membrane. As the hydrogen ions diffuse from the area of high concentration to the area of low concentration, the carrier protein harnesses the kinetic energy of the hydrogen ion to add a high-energy phosphate group to ADP forming ATP, with the help of the enzyme ATP synthetase.

Step 5.  The high-energy electron is passed along the electron transport chain until the excess energy is removed and then it is combined with the excess hydrogen ions and oxygen to form water, which then becomes a waste and must be removed from the system.

For an animated view see:  The electron transport chain (http://vcell.ndsu.edu/animations/etc/movie-flash.htm) - don't worry about the names of all the cytochrome enzymes!

In summary, the oxidation of glucose is approximately 37 percent efficient and produces all the energy required for almost every type of cell. The complete aerobic respiration of 1 molecule of glucose creates a maximum yield of 36 ATP molecules, as follows:
-Glycolysis = 4 ATP
- Kreb's cycle = 10 ATP
- Electron transport chain = 22 ATP 

If there is no O2 as a final acceptor, the whole system jams and another pathway must be followed:
FERMENTATION
-occurs when there is no O2
-after glycolysis, there are 2 pyruvates, 2 ATP's and 2 NADH + H+
-the reaction occurs in the cytosol
Image from http://www.bio.miami.edu/~cmallery/255/255atp/mcb8.5.fermentation.jpg

- no ATP is produced by fermentations, BUT NADH + H+ is used up and NAD+ is regenerated and returns to take part in glycolysis reactions, so glycolysis can continue (and produce some ATP).

Lactic acid fermentation occurs in some bacteria (this is how we make yogurt and cheese) and in most animals (this causes muscle pain)
Alcoholic fermentation occurs in bacteria and fungi (such as yeast).  We make use of it to make beer, wine, etc

-in general fermentation means that lots of energy is lost.  Fortunately, lactic acid can be changed back to pyruvate and run through biological oxidation when O2 is available. 

Metabolism of other Organic Compounds

- while carbohydrates are the major source of energy in the cell, other organic compounds may enter these cycles (although this is not the usual situation!)

Lipids:  fatty acids are oxidized to form many C2 molecules, which are converted into acetyl-CoAAcetyl-CoA enters the Kreb's cycle.  Glycerol is converted to PGAL, which enters glycolysis.

Proteins:  NH2 is removed and then resused or excreted.  Remaining C chains are broken down to many C2 molecules and converted to acetyl-CoA, which enters the Kreb's cycle.


Nucleic acids N parts are reused or excreted.  Pentose sugars are converted to PGAL, which enters glycolysis.


(Acetyl-CoA is an extremely important intermediary, which is found in many catabolic and anabolic reactions.)


Respiratory quotient (RQ) - Légzési hányados
-is a measure of the respiration (oxidation) rate
-determined by dividing the amount of CO2 evolved by the amount of O2 consumed.  It is usually about 0.8-0.9 in resting animals.

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