Glycolysis You only need to remember the details of the “net” Energy Investment Phase Glucose 2 ADP  2 P 2 ATP used Energy Payoff Phase 4 ADP  4 P 4 ATP formed 2 NAD  4 e−  4 H 2 NADH  2 H Glycolysis harvests chemical energy by oxidizing glucose to pyruvate. Glycolysis (“sugar splitting”) breaks down glucose into two molecules of pyruvate. Glycolysis occurs in the cytoplasm and has two major phases. Energy investment phase Energy payoff phase You only need to remember the details of the “net” 2 Pyruvate  2 H2O Net Glucose 2 Pyruvate  2 H2O 4 ATP formed − 2 ATP used 2 ATP 2 NAD  4 e−  4 H 2 NADH  2 H 1

Electrons via NADH and FADH2 Electrons via NADH Pyruvate oxidation Figure 7.6-2 Electrons via NADH and FADH2 Electrons via NADH Pyruvate oxidation Glycolysis Citric acid cycle Glucose Pyruvate Acetyl CoA CYTOSOL MITOCHONDRION Pyruvate oxidation and the citric acid cycle (aka the Krebs Cycle) (completes the breakdown of glucose) A small amount of ATP are formed by substrate level phosphorilation. : After pyruvate is oxidized, the citric acid cycle completes the energy-yielding oxidation of organic molecules. ATP ATP Substrate-level Substrate-level 2

In the presence of O2, pyruvate enters the mitochondrion (from glycolysis, 2 molecules per glucose) CYTOSOL Pyruvate is oxidized CO2 NAD CoA Before the citric acid cycle can begin, pyruvate must be converted to acetyl coenzyme A (acetyl CoA), which links glycolysis to the citric acid cycle. After glycolysis, pyruvate is oxidized to acetyl CoA. This junction between glycolysis and the citric acid cycle is shown in Figure 7.1. Note the following steps in the figure: A transport protein moves pyruvate from the cytosol into the matrix of the mitochondria. In the matrix an enzyme complex catalyzes three reactions: a CO2 is removed, electrons are stripped from pyruvate to convert NAD+ to NADH, and coenzyme A joins with the remaining two-carbon fragment to form acetyl CoA. NADH  H Acetyl CoA MITOCHONDRION CoA 3

Electrons via NADH and FADH2 Electrons via NADH Pyruvate oxidation Figure 7.6-2 Electrons via NADH and FADH2 Electrons via NADH Pyruvate oxidation Glycolysis Citric acid cycle Glucose Pyruvate Acetyl CoA CYTOSOL MITOCHONDRION ATP ATP Substrate-level Substrate-level 4

Oxidized Citric acid Reduced cycle Reduced Acetyl CoA CoA CoA 2 CO2 Figure 7.10b Citric Acid Cycle Acetyl CoA CoA Oxidized CoA Citric acid cycle Reduced 2 CO2 FADH2 3 NAD The citric acid cycle, also called the Krebs cycle, completes the breakdown of pyruvate to CO2. All along the citric acid cycle organic molecules are oxidized and NAD+ is reduced to become NADH and FAD is reduced to become FADH2. The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn. Because each glycose yields two pyruvates, the total products of the citric acid cycle are usually listed as the result of two cycles: 4CO2, 6 NADH, 2 FADH2, and 2 ATP. 3 NADH FAD  3 H Reduced ADP  P i ATP The NADH and FADH2 produced by the cycle relay electrons extracted from food to the electron transport chain. 5

Fun Fact If ATP could not be regenerated from ADP, humans would use up nearly their body weight in ATP each day.

Oxidative Phosphorylation Chapter 7 Oxidative Phosphorylation

You Must Know How electrons from NADH and FADH2 are passed to a series of electron acceptors to produce ATP by chemiosmosis. The roles of the mitochondrial membrane, proton (H+) gradient, and ATP synthase in generating ATP.

90% Electrons via NADH and FADH2 Electrons via NADH Oxidative Figure 7.6-3 Electrons via NADH and FADH2 Electrons via NADH Oxidative phosphorylation: electron transport and chemiosmosis Pyruvate oxidation Glycolysis Citric acid cycle Video Overview Glucose Pyruvate Acetyl CoA CYTOSOL MITOCHONDRION Concept 7.4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis. Following glycolysis and the citric acid cycle, NADH and FADH2 account for most of the energy extracted from food. These two electron carriers donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation. Oxidative phosphorylation accounts for most of the ATP synthesis. The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions. Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration. ATP ATP ATP Substrate-level Substrate-level Oxidative 90% 9

proton-motive force The electron transport chain is in the inner membrane (cristae) of the mitochondrion. Most of the chain’s components are proteins, which exist in multiprotein complexes. The carriers alternate reduced and oxidized states as they accept and donate electrons. Electrons drop in free energy as they go down the chain and are finally passed to O2, forming H2O. Electrons are transferred from NADH or FADH2 to the electron transport chain. Electron transfer in the electron transport chain causes proteins to pump H from the mitochondrial matrix to the intermembrane space. The electron transport chain generates no ATP directly. It breaks the large free-energy drop from food to O2 into smaller steps that release energy in manageable amounts.

proton-motive force H then moves back across the membrane, passing through the protein complex, ATP synthase. ATP synthase uses the exergonic flow of H to drive phosphorylation of ATP. This is an example of chemiosmosis, the use of energy in a H gradient to drive cellular work. The energy stored in a H gradient across a membrane couples the redox reactions of the electron transport chain to ATP synthesis. The H gradient is referred to as a proton-motive force, emphasizing its capacity to do work. ATP synthase uses the exergonic flow of H to drive phosphorylation of ATP.

Electron transport chain Oxidative phosphorylation Figure 7.14 H H Protein complex of electron carriers H H Cyt c IV Q III I ATP synthase II 2 H  ½ O2 H2O FADH2 FAD NADH NAD ADP  P ATP i (carrying electrons from food) H 1 Electron transport chain 2 Chemiosmosis Oxidative phosphorylation 13

electron transport chain  proton-motive force  ATP Electron shuttles span membrane CYTOSOL NADH FADH2 Glycolysis Glucose Pyruvate oxidation Acetyl CoA Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis  about 26 or 28 ATP  2 ATP About 30 or 32 ATP Maximum per glucose: MITOCHONDRION or About 34% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 32 ATP. ATP. During cellular respiration, most energy flows in the following sequence: glucose  NADH  electron transport chain  proton-motive force  ATP 14

Proteins Amino acids Carbohydrates Sugars Glucose Glycolysis Pyruvate Acetyl CoA Citric acid cycle NH3 Fats Glycerol Fatty Oxidative phosphorylation Carbohydrates Sugars Glycolysis Glucose Pyruvate Acetyl CoA You don’t need to memorize the details of the figure. You do need to remember the notes below. Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration. An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate. The body uses small molecules to build other substances. Some of these small molecules come directly from food; others can be produced during glycolysis or the citric acid cycle. Citric acid cycle Oxidative phosphorylation Citric acid cycle 15