The Killers Are Coming! The Killers Are Coming!

1. All active organisms, including the infamous killer bees, use energy on a steady basis.



2. Carbon dioxide and water are metabolic byproducts produced by living cells.



3. At the biochemical level, there is unity among all forms of life.

8.1   How Do Cells Make ATP?

1. ATP is the prime energy carrier for all cells.



2. Comparison of the Main Types of Energy-Releasing Pathways.
   
   
   1. Aerobic respiration (with oxygen) is the main pathway for energy release from carbohydrate to ATP.
   
   
   
   2. All energy-releasing pathways start with glycolysis.
      
      
      1. Glucose is split into two pyruvate molecules.
      
      
      
      2. Glycolysis reactions occur in the cytoplasm without the use of oxygen.


3. Overview of Aerobic Respiration
   
   
   1. Aerobic respiration yields thirty-six ATPs; fermentation yields merely two.
   
   
   
   2. The aerobic route is summarized:

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

   3. Three series of reactions are required for aerobic respiration:
      
      
      1. Glycolysis is the breakdown of glucose to pyruvate; small amounts of ATP are generated.
      
      
      
      2. Krebs cycle degrades pyruvate to carbon dioxide, water, ATP, H⁺ ions, and electrons (accepted by NAD⁺ and FAD).
      
      
      
      3. Electron transfer phosphorylation processes the H⁺ ions and electrons to generate high yields of ATP; oxygen is the final electron acceptor.

8.2   Glycolysis: First Stage of Energy-Releasing Pathways

1. Enzymes in the cytoplasm catalyze several steps in glucose breakdown.
   
   
   1. Glucose is first phosphorylated in energy-requiring steps, then the six-carbon intermediate is split to form two molecules of PGAL.
   
   
   
   2. Enzymes remove H⁺ and electrons from PGAL and transfer them to NAD⁺ which becomes NADH (used later in electron transfer).
   
   
   
   3. By substrate-level phosphorylation, four ATP are produced.


2. The end products of glycolysis are: two pyruvates, two ATP (net gain), and two NADH for each glucose molecule degraded.

8.3   Second Stage of the Aerobic Pathway

1. Preparatory Steps and the Krebs Cycle
   
   
   1. Pyruvate enters the mitochondria and is converted to acetyl-CoA, which then joins oxaloacetate already present from a previous "turn" of the cycle.
   
   
   
   2. During each turn of the cycle, three carbon atoms enter (as pyruvate) and three leave as three carbon dioxide molecules.


2. Functions of the Second Stage
   
   
   1. H⁺ and e^- are transferred to NAD⁺ and FAD.
   
   
   
   2. Two molecules of ATP are produced by substrate-level phosphorylation.
   
   
   
   3. Most of the molecules are recycled to conserve oxaloacetate for continuous processing of acetyl-CoA.
   
   
   
   4. Carbon dioxide is produced as a by-product.

8.4   Third Stage of the Aerobic Pathway

1. NADH and FADH₂ give up their electrons to transfer (enzyme) systems embedded in the mitochondrial inner membrane.



2. Electron Transfer Phosphorylation
   
   
   1. According to the chemiosmotic model, energy is released in the passage of electrons through components of the transfer series.
      
      
      1. The energy is used to pump hydrogen ions out of the inner compartment.
      
      
      
      2. When hydrogen ions flow back through the ATP synthase in the channels, the coupling of P_i to ADP yields ATP.
   
   
   2. Oxygen joins with the "spent" electrons and H⁺ to yield water.


3. Summary of the Energy Harvest
   
   
   1. Electron transfer yields thirty-two ATP; glycolysis yields two ATP; Krebs yields two ATP for a grand total of thirty-six ATP per glucose molecule.
   
   
   
   2. Normally, for every NADH produced within the mitochondria and processed by the electron transfer chain, three ATP are formed; FADH₂ yields two ATP.
   
   
   
   3. But NADH from the cytoplasm cannot enter the mitochondrion and must transfer its electrons!
      
      
      1. In most cells (skeletal, brain) the electrons are transferred to FAD and thus yield two ATP (for a total yield of thirty-six).
      
      
      
      2. But in liver, heart, and kidney cells, NAD⁺ accepts the electrons to yield three ATP; because two NADH are produced per glucose, this gives a total yield of thirty-eight ATP.

8.5   Anaerobic Routes of ATP Formation

1. Anaerobic pathways operate when oxygen is absent (or limited); pyruvate from glycolysis is metabolized to produce molecules other than acetyl-CoA.



2. Fermentation Pathways
   
   
   1. With an energy yield of only two ATPs, fermentation is restricted to single-celled organisms and cells of multicelled organisms only at certain limited times.
   
   
   
   2. Glycolysis serves as the first stage, just as it does in aerobic respiration.
   
   
   
   3. Lactate Fermentation
      
      
      1. Certain bacteria (as in milk) and muscle cells have the enzymes capable of converting pyruvate to lactate.
      
      
      
      2. No additional ATP beyond the net two from glycolysis is produced but NAD⁺ is regenerated.
   
   
   4. Alcoholic Fermentation
      
      
      1. Fermentation begins with glucose degradation to pyruvate.
      
      
      
      2. Cellular enzymes convert pyruvate to acetaldehyde, which then accepts electrons from NADH to become alcohol.
      
      
      
      3. Yeasts are valuable in the baking industry (carbon dioxide byproduct makes dough "rise") and in alcoholic beverage production.


3. Anaerobic Electron Transfer
   
   
   1. Some kinds of bacteria are able to strip electrons from organic compounds and send them through a special electron transfer in their membranes to produce ATP.
   
   
   
   2. Examples of such bacteria include those that reduce sulfate to hydrogen sulfide ( a foul-smelling gas indeed) and those that convert nitrate to nitrite.

8.6   Alternative Energy Sources in the Human Body

1. Carbohydrate Breakdown in Perspective.
   
   
   1. Excess carbohydrate intake is stored as glycogen in liver and muscle for future use.
   
   
   
   2. Free glucose is used until it runs low, then glycogen reserves are tapped.


2. Energy from Fats.
   
   
   1. Excess fats (including those made from carbohydrates) are stored away in cells of adipose tissue.
   
   
   
   2. Fats are digested into glycerol, which enters glycolysis, and fatty acids, which enter the Krebs cycle.
   
   
   
   3. Because fatty acids have many more carbon and hydrogen atoms, they are degraded more slowly and yield greater amounts of ATP.


3. Energy from Proteins
   
   
   1. Amino acids are released by digestion and travel in the blood.
   
   
   
   2. After the amino group is removed, the amino acid remnant is fed into the Krebs cycle.

8.7   Perspective on the Molecular Unity of Life

1. Photosynthesis and cellular respiration are intimately connected.



2. Life is not some mysterious force, but a series of chemical reactions under highly integrated control.

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