BIOL 425/001CH 6 NOTES: Respiration1. Overviewa. A preliminary step to respiration (the complete oxidation of sugars or other organic molecules to carbon dioxide and water) is the hydrolysis of the storagemolecules to the monosaccharides glucose and fructoseb. Respiration begins with glucosec. In the oxidation of glucose, the molecule is split apart, and the hydrogens (electrons) break off and combine with oxygen, thereby reducing O2, releasing free energyd. C6H12O6 + 6O2  6CO2 + 6H2O + energyi. Highly exergonicii. More energy released than through fermentatione. Processi. Glycolysis  pyruvateii. Pyruvate  acetyl CoAiii. Acetyl CoA  Citric Acid Cycleiv. Citric Acid Cycle  ETC (leads to oxidative phosphorylation)f. As the glucose molecule is oxidized, some energy is extracted in a series of small, discrete steps and is stored in the phosphoanhydride bonds of ATPg. Most energy is lost as heat2. Glycolysisa. The 6-Carbon glucose molecule is split into two molecules of pyruvateb. Occurs in 10 steps, each catalyzed by a specific enzymec. Anaerobic process occurring in the cytosold. Considered a primitive processe. 2 ATP are used for the reaction, but 4 ATP are formedf. 2 NADH are formed from NAD+g. Processi. Step 1: ATP donates a phosphate to glucose, forming glucose 6-phosphateii. Step 2: Glucose 6-phosphate is converted to fructose 6-phosphateiii. Step 3: fructose 6-phosphate gains another phosphate, becoming fructose 1,6-bisphosphateiv. Steps 4 and 5: the six carbon sugar is split in half, producing 2 glyceraldehyde 3-phosphatesv. Step 6: Two molecules of NAD+ are reduced to NADHvi. Steps 7 and 10: two molecules of ADP take energy from the system and form ATP – substrate-level phosphorylationh. Most energy is still presenti. Glucose +2NAD+ + 2ADP + 2Pi  2 Pyruvate + 2 NADH + 2 ATP + 2H2Oii. Most of the energy from the glucose makes it to the 2 pyruvates3. The Aerobic Pathwaya. Pyruvate is a key intermediateb. In presence of oxygen, pyruvate is oxidized to CO2c. The aerobic pathway occurs in the mitochondriai. Contains folds in the inner compartment called cristaeii. Within the inner compartment is the mitochondrial matrix, which contains enzymes, coenzymes, water, phosphates, and other moleculesiii. Mitochondria are like energy factoriesd. Pyruvate enters mitochondrion and is oxidized and decarboxylatedi. Electrons are removedii. CO2 is split out of the moleculeiii. NADH is produced for each pyruvateiv. Now the pyruvates have been oxidized to acetyl groupsv. The acetyl groups areattached to coenzyme A (CoA) (nucleotide plus pantothenic acid, B5)e. The citric acid cycle oxidizes the acetyl groupsi. Acetyl coA enters and the acetyl group is combined with oxaloacetate, producing citrateii. 2 of the 6 carbons are removed and oxidized to CO2iii. Oxaloacetate is regeneratediv. Each turn uses 1 molecule of Acetyl coA and regenerates 1 molecule ofoxaloacetatev. One molecule of ATP is formed per cyclevi. Three molecules of NADH are formedvii. One molecule of FADH2 is formed from FAD (another electron carrier)viii. Oxaloacetate + Acetyl CoA + 3H2O + ADP + P + 3NAD+ + FAD  Oxaloacetate + 2CO2 + CoA + ATP + 3NADH + 3H + FADH2f. Electrons are transferred to oxygen in the ETCi. The high energy electrons found in NADH and FADH2 are passed step by step to the low energy level of oxygenii. Made possible by the transporters of the ETCiii. Each carrier is capable of accepting or donating one or two electrons, and each carrier holds electrons at a slightly lower energy than the nextiv. Almost all carriers are in the mitochondrial membranev. Cytochromes1. Some carriers2. Protein molecules with an iron-containing porphyrin ring, or heme group3. Pick up electrons on the iron atoms which are reduced from Fe3+ (Ferric) to Fe2+ (Ferrous)4. In reduced form, cytochromes carry a single electron without a proteinvi. Iron-sulfur proteins1. The iron is not attached to a porphyrin ring, but to sulfides, andon the sulfur atoms of the sulfur-containing amino acids in the protein2. Picks up electrons on iron atomsvii. Coenzyme Q1. The most abundant components of the ETC are the quinone molecules2. CoQ is also known as ubiquinone3. Can accept or donate 1 or 2 electrons4. CoQ serves as an intermediate between two-electron carriers and one-electron carriers5. Picks up a proton with the electron, the equivalent of a hydrogen atom  can shuttle proteins across the inner mitochondrial membrane6. When an electron is released, the protein is released into the intermembrane space7. Forms a proton gradient across the inner mitochondrial membrane8. Can move among protein complexes in the ETC9. Moves freely within the lipid bilayerviii. NADH1. All electrons are donated to FMN (flavin mononucleotide)2. First component of the ETCix. FADH21. Electrons are transported to CoQ2. Farther down than FMNx. Released energy is harnessed and a proton gradient is formed by transferring protons from the matrix to the intermembrane spacexi. The proton gradient drives the formation of ATP form ADP and an inorganic P through oxidative phosphorylationxii. Each time one pair of electrons passes from NADH to oxygen, enough protons are pumped across the membrane to generate 3 molecules of ATPxiii. Each time a pair of electrons passes from FADH2, enough protons are pumped to form two molecules of ATPg. Oxidative phosphorylation is achieved by the chemiosmotic coupling mechanismi. Depends on a gradient of protons across the mitochondrial membrane and the subsequent use of the free energy stored in that gradient to form ATPii. There are 4 complexes in the mitochondrial membrane that have a relationship with the electron carriers (pp. 109)iii. The complexes are also proton pumpsiv. For each pair of electrons moved through the ETC, 10 protons are pumped out of the matrixv. Protons cannot easily move back through, producing a steep gradient1. Potential energy is created2. This creates an electrochemical gradient (number of moleculesplus the positive charge)vi. Powers ATP synthase – a large enzyme complex1. Embedded in the inner membrane of the mitochondria2. Has a binding site for ADP and phosphate as well as a channel that protons can pass throughvii. This mechanism is known as chemiosmotic coupling1. A proton gradient is established2. Potential energy stored in the gradient is used to generate ATPh. The overall energy harvest involves ATP, NADHand FADH2i. See balance sheet pp. 111Cytosol Matrix of MitochondrionElectron