How Cells Release Chemical Energy Chapter 8

Cellular or Aerobic Respiration Cellular respiration evolved to enable organisms to utilize energy stored in glucose. Taps the energy found in the bonds of organic compounds (carbohydrates, lipids, proteins)

Comparison of the Main Pathways Aerobic respiration Aerobic metabolic pathways (using oxygen) are used by most eukaryotic cells Ends in the mitochondria Aerobes use oxygen as the final electron acceptor Fermentation Anaerobic metabolic pathways (occur in the absence of oxygen) are used by prokaryotes and protists in anaerobic habitats Anaerobes use nitrate or sulfate as the final e- acceptor

Comparison of the Main Pathways Aerobic respiration and fermentation both begin with glycolysis, which converts one molecule of glucose into two molecules of pyruvate After glycolysis, the two pathways diverge Fermentation is completed in the cytoplasm, yielding 2 ATP per glucose molecule Aerobic respiration is completed in mitochondria, yielding 36 ATP per glucose molecule (liberates the most energy)

Overview of Aerobic Respiration Three sequential stages Glycolysis Acetyl-CoA formation and Krebs cycle Electron transfer phosphorylation (ATP formation) C6H12O6 (glucose) + O2 (oxygen) → CO2 (carbon dioxide) + H2O (water) Coenzymes NADH and FADH2

Figure 8.3 Overview of aerobic respiration. The reactions start in the cytoplasm and end inside mitochondria. The pathway’s inputs and outputs are summarized on the right. Figure It Out: What is aerobic respiration’s net yield of ATP? Answer: 38 – 2 = 36 ATP per glucose Fig. 8-3b, p. 125

Animation: Overview of aerobic respiration

8.2 Glycolysis – Glucose Breakdown Starts Glycolysis starts and ends in the cytoplasm of all prokaryotic and eukaryotic cells An energy investment/input of ATP (2) starts glycolysis Requires a continous supply of glucose and NAD+ (reduced in both glycolysis and the kreb cycle)

Glycolysis Two ATP’s are used to split glucose (6 carbon compound) and form 2 PGAL (3 carbon compound) Enzymes convert 2 PGAL to 2 PGA, forming 2 NADH Four ATP are formed by substrate-level phosphorylation (net yield of 2 ATP)

Figure 8.4 Glycolysis. This first stage of carbohydrate breakdown starts and ends in the cytoplasm of prokaryotic and eukaryotic cells. Glucose (right) is the reactant in the example shown on the opposite page; we track its six carbon atoms (black balls). Appendix VI shows the complete structures of the intermediates and the products. Fig. 8-4a (2), p. 126

fructose-1,6-bisphosphate (intermediate) ATP-Requiring Steps Glycolysis A An enzyme transfers a phosphate group from ATP to glucose, forming glucose-6-phosphate. glucose ATP ADP B A phosphate group from a second ATP is transferred to the glucose- 6- phosphate. The resulting molecule is unstable, and it splits into two three- carbon molecules. The molecules are interconvertible, so we will call them both PGAL (phosphoglyceraldehyde). glucose-6-phosphate ATP ADP Figure 8.4 Glycolysis. This first stage of carbohydrate breakdown starts and ends in the cytoplasm of prokaryotic and eukaryotic cells. Glucose (right) is the reactant in the example shown on the opposite page; we track its six carbon atoms (black balls). Appendix VI shows the complete structures of the intermediates and the products. fructose-1,6-bisphosphate (intermediate) So far, two ATP have been invested in the reactions. Fig. 8-4b (1), p. 127

The original energy investment of two ATP has now been recovered. ATP-Generating Steps C Enzymes attach a phosphate to the two PGAL, and transfer two electrons and a hydrogen ion from each PGAL to NAD+. Two PGA (phosphoglycerate) and two NADH are the result. 2 PGAL 2 NAD+ + 2 Pi NADH 2 reduced coenzymes D Enzymes transfer a phosphate group from each PGA to ADP. Thus, two ATP have formed by substrate-level phosphorylation. 2 PGA 2 ADP ATP The original energy investment of two ATP has now been recovered. 2 ATP produced by substrate-level phosphorylation E Enzymes transfer a phosphate group from each of two intermediates to ADP. Two more ATP have formed by substrate-level phosphorylation. 2 PEP 2 ADP Figure 8.4 Glycolysis. This first stage of carbohydrate breakdown starts and ends in the cytoplasm of prokaryotic and eukaryotic cells. Glucose (right) is the reactant in the example shown on the opposite page; we track its six carbon atoms (black balls). Appendix VI shows the complete structures of the intermediates and the products. ATP 2 ATP produced by substrate-level phosphorylation Two molecules of pyruvate form at this last reaction step. 2 pyruvate F Summing up, glycolysis yields two NADH, two ATP (net), and two pyruvate for each glucose molecule. Net 2 ATP + 2 NADH to second stage Fig. 8-4b (2), p. 127

8.3 Second Stage of Aerobic Respiration The second stage of aerobic respiration finishes breakdown of glucose that began in glycolysis Occurs in mitochondria (inner compartment) begans with the chemical pyruvate to continue respiration Includes two stages: acetyl CoA formation and the Krebs cycle (each occurs twice in the breakdown of one glucose molecule)

The Krebs Cycle Krebs cycle A sequence of enzyme-mediated reactions that break down 1 acetyl CoA (transition stage) into 2 CO2 Oxaloacetate (last intermediate) is used and regenerated 3 NADH and 1 FADH2 are formed, 1 ATP is formed Substrate level phosphorylation occurs Electrons and hydrogens are transferred to coenzymes in both glycolysis and the Kreb cycle Energy, CO2, and H+ are released Cycle turns 2x to break down glucose

Acetyl–CoA Formation transition from glyco A An enzyme splits a pyruvate molecule into a two-carbon acetyl group and CO2. Coenzyme A binds the acetyl group (forming acetyl–CoA). NAD+ combines with released hydrogen ions and electrons, forming NADH. NADH pyruvate CO2 NAD+ coenzyme A acetyl–CoA B The Krebs cycle starts as one carbon atom is transferred from acetyl–CoA to oxaloacetate. Citrate forms, and coenzyme A is regenerated. oxaloacetate coenzyme A citrate Krebs Cycle H The final steps of the Krebs cycle regenerate oxaloacetate. NADH G NAD+ combines with hydrogen ions and electrons, forming NADH. NAD+ C A carbon atom is removed from an intermediate and leaves the cell as CO2. NAD+ combines with released hydrogen ions and electrons, forming NADH. NADH CO2 NAD+ Figure 8.6 Aerobic respiration’s second stage: acetyl–CoA formation and the Krebs cycle. One set of second-stage reactions converts one pyruvate to three CO2 for a yield of one ATP, four NADH, and one FADH2 (right). The reactions occur in the mitochondrion’s inner compartment. For simplicity, many of the pathway’s intermediates are not shown. See Appendix VI for the detailed reactions. FADH2 F The coenzyme FAD com-bines with hydrogen ions and electrons, forming FADH2. FAD Pyruvate’s three carbon atoms have now exited the cell, in CO2. D A carbon atom is removed from another intermediate and leaves the cell as CO2, and another NADH forms. NADH CO2 NAD+ ATP E One ATP forms by substrate-level phosphorylation. ADP + Pi Stepped Art Fig. 8-6, p. 129

Animation: The Krebs Cycle - details

8.4 Aerobic Respiration’s Big Energy Payoff Many ATP’s are formed during the third and final stage of aerobic respiration (Chemiosmotic Theory = production of ATP’s) Electron transfer phosphorylation Occurs in mitochondria (inner membrane) Results in attachment of phosphate to ADP to form ATP Generates a hydrogen concentration (build up of hydrogen ions between 2 membranes) gradient

Electron Transfer Phosphorylation

Summary: The Energy Harvest Typically, the breakdown of one glucose molecule yields 36 ATP Glycolysis: 2 ATP Acetyl CoA formation and Krebs cycle: 2 ATP Electron transfer phosphorylation: 32 ATP

Animation: Third-stage reactions

8.5 Anaerobic Energy-Releasing Pathways Fermentation pathways break down carbohydrates without using oxygen (Ex. Bacteria that causes botulism) The final steps in these pathways regenerate NAD+

Fermentation Pathways Glycolysis is the first stage of fermentation Forms 2 pyruvate, 2 NADH, and 2 ATP Pyruvate turns to lactic acid using e- from NADH (Lactate/Lactose Fermentation) Pyruvate is converted to ethanol producing acetaldehyde and CO2 (Alcoholic Fermentation)

Two Pathways of Fermentation Alcoholic fermentation Pyruvate produce acetaldehyde and CO2 when converted to ethanol Acetaldehyde receives electrons and hydrogen from NADH, forming NAD+ and ethanol Lactate fermentation Pyruvate receives electrons and hydrogen from NADH, forming NAD+ and lactate (muscle cells, sour cream, etc)

Alcoholic Fermentation 2 CO2 Glycolysis glucose 2 NAD+ 2 ATP NADH 4 pyruvate glucose Glycolysis 2 NAD+ 2 ATP NADH pyruvate 4 2 NADH 2 NAD+ ethanol 2 NADH 2 NAD+ Alcoholic Fermentation 2 CO2 acetaldehyde Lactate Fermentation lactate Figure 8.9 (a) Alcoholic fermentation. (b) Lactate fermentation. In both pathways, the final steps do not produce ATP. They regenerate NAD+. The net yield is two ATP per molecule of glucose (from glycolysis). Stepped Art Fig. 8-9, p. 132

8.6 The Twitchers Slow-twitch muscle fibers (“red” muscles) make ATP by aerobic respiration Have many mitochondria Dominate in prolonged activity Fast-twitch muscle fibers (“white” muscles) make ATP by lactate fermentation Have few mitochondria and no myoglobin Sustain short bursts of activity Human muscles have a mixture of both fibers

8.7 Alternative Energy Sources in the Body In humans and other mammals, the entrance of glucose and other organic compounds into an energy-releasing pathway depends on the kinds and proportions of carbohydrates (our main source of energy), fats and proteins in the diet

The Fate of Glucose at Mealtime and Between Meals When blood glucose concentration rises, the pancreas increases insulin (hormone) secretion Cells take up glucose faster, more ATP is formed When blood glucose concentration falls, the pancreas increases glucagon (hormone) secretion (between meals) Stored glycogen is converted to glucose, the brain continues to receive glucose Triglycerides are tapped as an energy alternative.

Energy From Fats About 78% of an adult’s energy reserves is stored in fat (mostly triglycerides) Excess glucose(carbs) in the diet = FAT; acetyl Co A exits the Kreb Cycle and enters a pathway that makes fatty acids Enzymes cleave fats into glycerol and fatty acids Glycerol products enter glycolysis Fatty acid products enter the Krebs cycle

Energy from Proteins Enzymes split dietary proteins into amino acid subunits, which enter the bloodstream Used to build proteins or other molecules Excess amino acids are broken down into ammonia (NH3) and various products that can enter the Krebs cycle

Electron Transfer Phosphorylation FOOD FATS COMPLEX CARBOHYDRATES PROTEINS fatty acids glycerol glucose, other simple sugars amino acids acetyl–CoA PGAL acetyl–CoA Glycolysis NADH pyruvate oxaloacetate or another intermediate of the Krebs Figure 8.12 Reaction sites where a variety of organic compounds enter aerobic respiration. Such compounds are alternative energy sources in the human body. In humans and other mammals, complex carbohydrates, fats, and proteins from food do not enter the pathway of aerobic respiration directly. First, the digestive system, and then individual cells, break apart all of these molecules into simpler subunits. We return to this topic in Chapter 40. Krebs Cycle NADH, FADH2 Electron Transfer Phosphorylation Fig. 8-12, p. 135