Chapter 9 Cellular respiration and fermentation (Dr. Raf ppt)

Overview of Respiration

• Glycolysis

  • This is the first step where one glucose molecule, a 6-carbon sugar, is broken down or "oxidized" into two smaller molecules called pyruvate, which each have 3 carbons.

  • It happens in the cytoplasm (the jelly-like substance) outside the cell's powerhouses, the mitochondria.

  • No oxygen is needed for glycolysis to occur, making it an anaerobic (without oxygen) process.

  • It creates a small amount of ATP (cellular energy) by directly transferring a phosphate group to ADP, a process known as substrate-level phosphorylation. It also produces electron carriers called NADH.

• Pyruvate Oxidation

  • This step acts as a bridge, preparing the pyruvate molecules to enter the next stage.

  • It takes place inside the mitochondrial matrix (the innermost compartment of the mitochondrion).

  • Each pyruvate is converted into an Acetyl-CoA molecule, releasing carbon dioxide (CO2CO2​) and generating more NADH.

• Citric Acid Cycle (Krebs Cycle/TCA Cycle)

  • This cycle completely finishes the breakdown (oxidation) of the original glucose molecule. The Acetyl-CoA from pyruvate oxidation enters this cycle.

  • It also occurs in the mitochondrial matrix.

  • It produces a small amount of ATP (or GTP, which is similar to ATP) through substrate-level phosphorylation, along with a lot of high-energy electron carriers (more NADH and FADH₂).

• Oxidative Phosphorylation (OxPhos)

  • This is the stage where most of the ATP is generated, using the energy from the high-energy electrons collected by NADH and FADH₂.

  • It happens on the inner mitochondrial membrane.

  • It involves two main parts:

    1. ETC (Electron Transport Chain): A series of proteins that pass electrons along, gradually releasing their energy.

    2. Chemiosmosis: Uses the energy released by the ETC to make a large amount of ATP.

Detailed Process of Cellular Respiration

Glycolysis

1. Overview

   • Glycolysis literally means "sugar splitting." It occurs in the cytosol (the fluid part of the cytoplasm) of the cell, outside the mitochondria.

   • It's a ten-step process, with each step helped by a specific enzyme.

   • It begins with one molecule of glucose (6 carbons).

   • The glucose molecule is first activated by adding phosphate groups, which makes it unstable and easier to split.

   • This 'activation' uses a small amount of ATP in what's called the Energy Investment Phase.

2. Energy Investment Phase (1st1st - 5th5th steps)

   • Costs 2 ATP molecules: Two ATPs are used to attach phosphate groups to the glucose molecule. This turns glucose into fructose-1,6-bisphosphate.

   • Splits Glucose: This 6-carbon molecule then splits into two identical 3-carbon molecules called glyceraldehyde-3-phosphate (G3P).

   • Think of it like priming a pump: you put in a little energy to get a lot more out later.

3. Energy Payoff Phase (6th6th - 10th10th steps)

   • Now, the two G3P molecules are processed, and the cell reclaims its energy investment, plus more.

   • Electron Carriers (NADH) are Generated: For each of the two 3-carbon G3P molecules, electrons are removed and transferred to the electron carrier NAD⁺, turning it into NADH. This means 2 NADH are produced in total.

   • Water Production: Each 3-carbon molecule also generates one molecule of water (H2OH2O), so 2 H2OH2O are produced in total.

   • ATP is Produced Directly: Through substrate-level phosphorylation, phosphate groups are directly transferred from a substrate molecule to ADP, making ATP. This creates 2 ATP per 3-carbon molecule, for a total of 4 ATP made.

   • Net Gain of ATP: Since 2 ATP were used in the investment phase and 4 ATP were made, the net gain from glycolysis is 2 ATP.

   • No Oxygen or CO₂: Remember, oxygen is still not needed for any of these steps, and no carbon dioxide is released.

4. Summary of Glycolysis: Inputs and Outputs (Net)

   • What Goes In (Net Inputs): 1 Glucose molecule, 2 NAD⁺ (which become NADH), and a net consumption of 2 ATP (though 4 are made, 2 are used).

   • What Comes Out (Net Outputs): 2 Pyruvate molecules, 2 NADH, and a net gain of 2 ATP.

Pyruvate Oxidation (or Decarboxylation)

• After glycolysis, the two pyruvate molecules need to be modified before they can enter the Krebs Cycle.

• They are actively moved from the cytoplasm into the mitochondrial matrix.

• A large group of enzymes, called the pyruvate dehydrogenase complex, performs these changes for each pyruvate molecule:

  1. Carbon Dioxide Release (Decarboxylation): A carboxyl group (COO−COO−) is removed from each pyruvate and released as a molecule of carbon dioxide (CO2CO2​). This means the 3-carbon pyruvate becomes a 2-carbon molecule.

  2. Electron Transfer (Oxidation): The remaining 2-carbon molecule is oxidized, meaning it loses electrons. These electrons are picked up by NAD⁺, reducing it to NADH. This carrier will take its energy to the ETC.

  3. Coenzyme A Attachment: A molecule called Coenzyme A (CoA) attaches to the 2-carbon fragment, forming Acetyl-CoA. This Acetyl-CoA is now ready to enter the Krebs Cycle.

• Yield (per glucose molecule, since 2 pyruvates are processed): 2 CO₂, 2 NADH, and 2 Acetyl-CoA molecules.

Krebs Cycle (Citric Acid Cycle)

1. Overview

   • This cycle, also known as the tricarboxylic acid (TCA) cycle, consists of 8 steps, each facilitated by a specific enzyme, and it forms a continuous loop.

   • Each Acetyl-CoA (a 2-carbon molecule) enters the cycle by combining with a 4-carbon molecule called Oxaloacetate. This creates a 6-carbon molecule known as Citrate (citric acid).

   • The amazing part is that Oxaloacetate is regenerated at the end of each cycle, so it's ready to accept another Acetyl-CoA, keeping the cycle going.

2. Processes and Outputs (for each single turn of the cycle, which means per Acetyl-CoA)

   • During each turn, the 6-carbon citrate molecule is systematically broken down:

     • Carbon Dioxide Release: Two carbon atoms from the original Acetyl-CoA are fully oxidized and released as 2 CO₂ molecules.

     • Electron Carrier Production: A lot of high-energy electrons are captured:

       • 3 NADH molecules are produced as NAD⁺ accepts electrons.

       • 1 FADH₂ molecule is produced as FAD accepts electrons.

     • Direct ATP Production: 1 ATP (sometimes as GTP, which quickly converts to ATP) is produced via substrate-level phosphorylation.

   • Total Yield per Glucose Molecule: Since one glucose molecule yields two pyruvates, which then yield two Acetyl-CoA molecules, the Krebs cycle actually runs twice for every original glucose molecule. Therefore, for one glucose:

     • 4 CO₂ (2 from each turn)

     • 6 NADH (3 from each turn) (This is in addition to the 2 NADH from glycolysis and 2 NADH from pyruvate oxidation)

     • 2 FADH₂ (1 from each turn)

     • 2 ATP (or GTP) (1 from each turn)

Oxidative Phosphorylation

• This is the final and most productive stage for ATP synthesis, making nearly 90% of the ATP in aerobic respiration. It literally means "adding phosphate using oxygen."

• It combines two processes: the electron transport chain (ETC) and chemiosmosis.

• The high-energy electrons carried by NADH and FADH₂ (from previous stages) are delivered to the ETC, located in the inner mitochondrial membrane.

• The overall goal is to gradually extract energy from these electrons to create a special energy gradient, which then powers ATP production.

• Electron Transport Chain (ETC)

  • The ETC is a series of four large protein complexes (called Complex I, II, III, and IV) embedded in the inner mitochondrial membrane, along with small mobile carriers (Ubiquinone and Cytochrome c).

  • Electron Flow: Think of the ETC as a series of downhill steps for electrons. NADH and FADH₂ drop off their electrons. NADH delivers electrons to Complex I, and FADH₂ delivers them to Complex II. These electrons then move sequentially through the other complexes (III and IV) via the mobile carriers.

  • Proton Pumping: As electrons pass from one complex to the next, they release small amounts of energy. This energy is used by Complexes I, III, and IV to act as "pumps," actively moving protons (H⁺ ions) from the mitochondrial matrix (the innermost part) into the intermembrane space (the area between the inner and outer mitochondrial membranes).

  • Terminal Electron Acceptor: At the very end of the chain, after passing through all the complexes, the electrons are finally handed off to molecular oxygen (O2O2). Oxygen is crucial here; it acts as the "final electron acceptor." When oxygen accepts these electrons and combines with protons, it forms water (H2OH2O).

Chemiosmosis

1. Mechanism

   • Proton Gradient: The continuous pumping of H⁺ ions into the intermembrane space creates a proton gradient. This means there's a much higher concentration of H⁺ ions in the intermembrane space than in the matrix. This difference in concentration, along with the electrical charge difference (more positive in the intermembrane space), creates a strong potential energy, much like water held behind a dam. This energy is called the proton-motive force (PMF).

   • ATP Synthase: The inner mitochondrial membrane also contains a remarkable enzyme complex called ATP Synthase. This complex acts like a tiny turbine or an enzyme-channel combination. The high concentration of protons in the intermembrane space causes them to want to flow back into the matrix, following their concentration gradient.

   • ATP Production: The only way for these protons to flow back is through the ATP Synthase channel. As H⁺ ions pass through ATP Synthase, their physical movement causes parts of the enzyme to rotate. This mechanical energy is harnessed by the enzyme to drive the chemical reaction of adding a phosphate group to ADP, actively synthesizing large amounts of ATP from ADP and inorganic phosphate (PiPi​).

   • Thus, the energy of the proton-motive force is brilliantly converted into the chemical energy stored in ATP.

2. Importance of Oxygen

   • Oxygen is absolutely essential for the entire process of oxidative phosphorylation to work effectively.

   • If oxygen is not available, there's no final acceptor for the electrons in the ETC. The electrons get backed up, and the ETC stops functioning.

   • If the ETC stops, protons cannot be pumped, and the proton gradient necessary for ATP synthase to work cannot be established.

   • This means that most ATP synthesis stops almost immediately. Also, the electron carriers (NADH and FADH₂) cannot unload their electrons, so they remain in their reduced state and cannot be regenerated. This effectively halts the Krebs cycle and pyruvate oxidation, as they depend on NAD⁺ and FAD being available.

Summary of ATP Yield in Cellular Respiration

• The complete breakdown of one glucose molecule through aerobic respiration yields approximately 30-32 ATP molecules.

• This number is an estimate because factors like the shuttle system used to transport NADH electrons into the mitochondria (different systems yield different amounts) and other minor energy losses can affect the final count.

• The efficiency of energy transfer from glucose to ATP is around 34%. The remaining energy is lost primarily as heat, which helps maintain body temperature in warm-blooded organisms but is part of the inefficiency of energy conversion.

Anaerobic Respiration and Fermentation

1. Definition

   • When oxygen is absent or very scarce, cells must find alternative ways to produce ATP. This leads to either anaerobic respiration or fermentation.

   • Anaerobic Respiration: This process still uses an electron transport chain and chemiosmosis, similar to aerobic respiration. However, instead of oxygen, it uses a different molecule as the terminal electron acceptor (like sulfate (SO42−SO42−), nitrate (NO3−NO3−, or elemental sulfur). It usually produces less ATP than aerobic respiration (e.g., about 21-24 ATP per glucose).

   • Fermentation: This process does NOT use an electron transport chain. Its primary purpose is to regenerate NAD⁺ from NADH so that glycolysis can continue to produce its modest 2 ATP. It is a much less efficient way to make ATP, producing only 2 ATP per glucose (from glycolysis alone).

2. Types of Fermentation

   • Alcoholic Fermentation: In this process (common in yeast and some bacteria), pyruvate is first converted into acetaldehyde, releasing CO2CO2​. Then, acetaldehyde accepts electrons from NADH, becoming ethanol (alcohol) and regenerating NAD⁺. This NAD⁺ can then be used again in glycolysis.

   • Lactic Acid Fermentation: In this process (common in muscle cells during intense exercise when oxygen supply is low, and also in many bacteria used to make yogurt or cheese), pyruvate directly accepts electrons from NADH, converting into lactic acid (lactate) and regenerating NAD⁺. This buildup of lactic acid can cause muscle soreness.

3. Comparison of Anaerobic Processes

   • Obligate Anaerobes: These organisms can only survive and produce energy in environments without oxygen. Oxygen is actually toxic to them.

   • Facultative Anaerobes: These organisms are flexible. They can switch between aerobic respiration (when oxygen is available, which is more efficient) and anaerobic processes like fermentation (when oxygen is scarce or absent) to meet their energy needs.

Catabolic Versatility

• Cellular respiration isn't only about breaking down glucose. The pathways are flexible and can process other types of food molecules too:

  • Lipids (Fats): Fats are excellent sources of energy. They are broken down into glycerol and fatty acids. Glycerol can enter glycolysis, while fatty acids undergo a process called beta-oxidation to be converted into Acetyl-CoA, which then directly enters the Krebs cycle.

  • Proteins: Proteins are broken down into their amino acid building blocks. The amino acids have their amino groups removed (a process called deamination). The remaining carbon skeletons can then enter glycolysis, pyruvate oxidation, or the Krebs cycle at various points, depending on their structure.

  • Carbohydrates (Polysaccharides and Disaccharides): Complex carbohydrates like starch (polysaccharide) or sucrose (disaccharide) are first broken down (hydrolyzed) into simpler monosaccharide units, like glucose, which then enter glycolysis.

Regulation of Respiration

• The cell carefully controls the rate of cellular respiration to match its energy (ATP) needs. This is primarily done through feedback mechanisms.

• One key regulatory enzyme is Phosphofructokinase, which is an enzyme in glycolysis. It essentially commits the glucose molecule to the glycolysis pathway. Its activity is controlled by:

  • Inhibition: High levels of ATP (meaning the cell has enough energy) and citrate (an intermediate of the Krebs cycle, indicating the cycle is busy) will inhibit phosphofructokinase. This slows down glycolysis and thus the entire respiration process, preventing wasteful energy production.

  • Stimulation: High levels of AMP (adenosine monophosphate, which is similar to ADP but with only one phosphate, signaling very low energy) will stimulate phosphofructokinase. This speeds up glycolysis and ATP production when the cell desperately needs energy.

Vocabulary

• Glycolysis: The initial breakdown of glucose into pyruvate in the cytoplasm, producing a small amount of ATP and NADH without oxygen.

• Substrate-Level Phosphorylation: A direct method of ATP synthesis where a phosphate group is transferred from an organic substrate to ADP.

• Pyruvate: The 3-carbon end product of glycolysis.

• Acetyl-CoA: A 2-carbon molecule formed from pyruvate, which enters the Krebs cycle.

• Oxaloacetate: A 4-carbon molecule that combines with Acetyl-CoA to start the Krebs cycle and is regenerated at the end.

• Oxidative Phosphorylation: The process using the electron transport chain and chemiosmosis to produce the majority of ATP in aerobic respiration.

• Electron Transport Chain: A series of protein complexes on the inner mitochondrial membrane that pass electrons to pump protons.

• Proton Gradient: A difference in proton (H⁺) concentration across a membrane, storing potential energy.

• Proton-Motive Force: The potential energy stored in the proton gradient, used to drive ATP synthesis.

• ATP Synthase: An enzyme complex that uses the energy from the proton-motive force to synthesize ATP from ADP and PiPi​.

• Terminal Electron Acceptor: The final molecule that accepts electrons at the end of an electron transport chain; oxygen in aerobic respiration.

• Anaerobic Respiration: Respiration that uses an ETC with a terminal electron acceptor other than oxygen.

• Fermentation (Lactic Acid vs. Alcohol): Metabolic pathways that regenerate NAD⁺ from NADH without an ETC, producing either lactic acid or ethanol and CO2CO2​.

• Obligate Anaerobes: Organisms that can only survive in the absence of oxygen.

• Facultative Anaerobes: Organisms that can switch between aerobic respiration and fermentation depending on oxygen availability.

• Aerobic Respiration: A process that requires oxygen to produce ATP through an electron transport chain with oxygen as the terminal electron acceptor.