chapter 10

• Glycolysis


  The first step in the breakdown of glucose to extract energy for cellular metabolism
• Nearly all of the energy used by living cells comes from the energy in the bonds of the sugar glucose
• Glucose transport into cells

  • Secondary active transport against concentration gradient
  • Facilitated diffusion using GLUT proteins
• Glycolysis is the first pathway used in the breakdown of glucose to extract energy
• Glycolysis takes place in the cytoplasm of both prokaryotic and eukaryotic cells
• Glycolysis is anaerobic, it does not use oxygen
• Glycolysis


  The first of the main metabolic pathways of cellular respiration to produce energy in the form of ATP
• Glycolysis

  1. Energy-requiring steps

  2. Energy-releasing steps
• Glycolysis produces a net gain of two pyruvate molecules, two ATP molecules, and two NADH molecules
• Following glycolysis, the pathway is linked to the Krebs Cycle, where further ATP will be produced
• Hexokinase


  • Catalyzes the phosphorylation of six-carbon sugars using ATP
• Phosphofructokinase


  • A rate-limiting enzyme in glycolysis, active when ADP is high and less active when ATP is high
• Aldolase


  • Cleaves fructose-1,6-bisphosphate into two three-carbon isomers
• Glyceraldehyde-3-phosphate dehydrogenase

  • Oxidizes glyceraldehyde-3-phosphate, extracting high-energy electrons which reduce NAD+ to NADH
• Phosphoglycerate kinase


  • Catalyzes substrate-level phosphorylation, producing one ATP molecule
• Pyruvate kinase


  • Catalyzes the last step of glycolysis, producing one ATP molecule
• Glycolysis produces a net gain of 2 ATP and 2 NADH molecules from one glucose molecule
• Mature red blood cells rely solely on glycolysis for ATP production as they lack mitochondria
• If NAD+ is unavailable, the second half of glycolysis slows or stops
• Pyruvate kinase is a rate-limiting enzyme for glycolysis
• Citric acid cycle


  A series of reactions that produces 2 CO2 molecules, 1 GTP/ATP, and reduced NADH and FADH2
• The citric acid cycle takes place in the matrix of the mitochondria
• Steps of the citric acid cycle

  1. Condensation

  2. Isomerization

  3. Oxidation and decarboxylation

  4. Substrate-level phosphorylation

  5. Dehydration
• The citric acid cycle produces very little ATP directly and does not directly consume oxygen
• The citric acid cycle is an aerobic pathway as the NADH and FADH2 produced must transfer electrons to the next pathway which uses oxygen
• Regulated


  By feedback inhibition of ATP, succinyl CoA, and NADH
• Step 5

  1. A phosphate group is substituted for coenzyme A, and a high-energy bond is formed

  2. This energy is used in substrate-level phosphorylation (during the conversion of the succinyl group to succinate) to form either guanine triphosphate (GTP) or ATP

  3. There are two forms of the enzyme, called isoenzymes, for this step, depending upon the type of animal tissue in which they are found

  4. One form is found in tissues that use large amounts of ATP, such as heart and skeletal muscle, and this form produces ATP

  5. The second form of the enzyme is found in tissues that have a high number of anabolic pathways, such as liver, and this form produces GTP
• Step 6

  1. A dehydration process that converts succinate into fumarate

  2. Two hydrogen atoms are transferred to FAD, producing FADH2

  3. The energy contained in the electrons of these atoms is insufficient to reduce NAD+ but adequate to reduce FAD

  4. Unlike NADH, this carrier remains attached to the enzyme and transfers the electrons to the electron transport chain directly

  5. This process is made possible by the localization of the enzyme catalyzing this step inside the inner membrane of the mitochondrion
• Step 7

  1. Water is added to fumarate, and malate is produced

  2. The last step in the citric acid cycle regenerates oxaloacetate by oxidizing malate

  3. Another molecule of NADH is produced
• Products of the Citric Acid Cycle

  • Two carbon atoms come into the citric acid cycle from each acetyl group, representing four out of the six carbons of one glucose molecule
  • Two carbon dioxide molecules are released on each turn of the cycle
  • The two acetyl carbon atoms will eventually be released on later turns of the cycle, so all six carbon atoms from the original glucose molecule are eventually incorporated into carbon dioxide
  • Each turn of the cycle forms three NADH molecules and one FADH2 molecule
  • These carriers will connect with the last portion of aerobic respiration to produce ATP molecules
  • One GTP or ATP is also made in each cycle
  • Several of the intermediate compounds in the citric acid cycle can be used in synthesizing non-essential amino acids, so the cycle is amphibolic (both catabolic and anabolic)
• Breakdown of Pyruvate


  1. Pyruvate is converted into acetyl CoA in order to enter the citric acid cycle

  2. A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide

  3. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH

  4. The enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA
• Electron Transport Chain


  • Uses the electrons from electron carriers to create a chemical gradient that can be used to power oxidative phosphorylation
  • Oxidative phosphorylation is a highly efficient method of producing large amounts of ATP, the basic unit of energy for metabolic processes
  • During this process electrons are exchanged between molecules, which creates a chemical gradient that allows for the production of ATP
  • The most vital part of this process is the electron transport chain, which produces more ATP than any other part of cellular respiration
• Electron Transport Chain

  • The final component of aerobic respiration and the only part of glucose metabolism that uses atmospheric oxygen
  • Electron transport is a series of redox reactions that resemble a relay race
  • Electrons are passed rapidly from one component to the next to the endpoint of the chain, where the electrons reduce molecular oxygen, producing water
  • The electron transport chain is an aggregation of four complexes (labeled I through IV), together with associated mobile electron carriers
  • The electron transport chain is present in multiple copies in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes
• Complex I


  1. Two electrons are carried to the first complex aboard NADH

  2. Complex I is composed of flavin mononucleotide (FMN) and an enzyme containing iron-sulfur (Fe-S)

  3. FMN is one of several prosthetic groups or co-factors in the electron transport chain

  4. The enzyme in complex I is NADH dehydrogenase, a very large protein containing 45 amino acid chains

  5. Complex I can pump four hydrogen ions across the membrane from the matrix into the intermembrane space
• Q and Complex II


  • Complex II directly receives FADH2, which does not pass through complex I
  • The compound connecting the first and second complexes to the third is ubiquinone (Q)
  • Q receives the electrons derived from NADH from complex I and the electrons derived from FADH2 from complex II, including succinate dehydrogenase
  • Since these electrons bypass, and thus do not energize, the proton pump in the first complex, fewer ATP molecules are made from the FADH2 electrons
  • The number of ATP molecules ultimately obtained is directly proportional to the number of protons pumped across the inner mitochondrial membrane
• Complex III


  • Composed of cytochrome b, another Fe-S protein, Rieske center (2Fe-2S center), and cytochrome c proteins
  • Cytochrome proteins have a prosthetic heme group
  • The heme molecule carries electrons, not oxygen, and the iron ion at its core is reduced and oxidized as it passes the electrons, fluctuating between different oxidation states
  • Complex III pumps protons through the membrane and passes its electrons to cytochrome c for transport to the fourth complex
• Complex IV


  • Composed of cytochrome proteins c, a, and a3
  • Contains two heme groups (one in each of the cytochromes a and a3) and three copper ions (a pair of CuA and one CuB in cytochrome a3)
  • The cytochromes hold an oxygen molecule very tightly between the iron and copper ions until the oxygen is completely reduced
  • The reduced oxygen then picks up two hydrogen ions from the surrounding medium to produce water (H2O)
  • The removal of the hydrogen ions from the system also contributes to the ion gradient used in the process of chemiosmosis
• Chemiosmosis


  • The movement of ions across a selectively permeable membrane, down their electrochemical gradient
  • During chemiosmosis, electron carriers like NADH and FADH donate electrons to the electron transport chain
  • The electrons cause conformation changes in the shapes of the proteins to pump H+ across a selectively permeable cell membrane
  • The uneven distribution of H+ ions across the membrane establishes both concentration and electrical gradients (thus, an electrochemical gradient) owing to the hydrogen ions' positive charge and their aggregation on one side of the membrane
  • The hydrogen ions in the matrix space can only pass through the inner mitochondrial membrane through a membrane protein called ATP synthase
  • This protein acts as a tiny generator turned by the force of the hydrogen ions diffusing through it, down their electrochemical gradient
  • The turning of this molecular machine harnesses the potential energy stored in the hydrogen ion gradient to add a phosphate to ADP, forming ATP
• Oxidative Phosphorylation


  • The production of ATP using the process of chemiosmosis in mitochondria
  • It is the method used in the light reactions of photosynthesis to harness the energy of sunlight in the process of photophosphorylation
  • The overall result of these reactions is the production of ATP from the energy of the electrons removed from hydrogen atoms, which were originally part of a glucose molecule
  • At the end of the pathway, the electrons are used to reduce an oxygen molecule to oxygen ions, and the extra electrons on the oxygen attract hydrogen ions (protons) from the surrounding medium to form water
• ATP Yield


  • In a eukaryotic cell, the process of cellular respiration can metabolize one molecule of glucose into 30 to 32 ATP
  • The process of glycolysis only produces two ATP, while all the rest are produced during the electron transport chain
  • The number of ATP molecules generated can vary due to factors like the number of hydrogen ions the electron transport chain complexes can pump through the membrane, the shuttle of electrons across the membranes of the mitochondria, and the use of intermediate compounds for other purposes