Chapter 7 How Cells Release Chemical Energy

7.1 Risky Business An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation is a chemical reaction that can produce free radicals, leading to chain reactions that may damage cells.  Antioxidants such as thiols or ascorbic acid (vitamin C) terminate these chain reactions. Early life on Earth lived in anaerobic (oxygen-free) environments Some organisms lived and thrived in aerobic (O2-containing) environments Produced antioxidants that detoxify or prevent free radical formation Over time, aerobic respiration evolved Produces ATP very efficiently Occurs inside mitochondria

Mitochondrial Malfunction Aerobic respiration still produces oxygen free radicals Failure to remove free radicals results in oxidative stress Oxidative stress is linked to illnesses such as Alzheimer’s and Parkinson’s diseases Nerve cells are particularly sensitive: have a need for a large number of mitochondria and high ATP

7.2 Overview of Carbohydrate Breakdown Pathways Photosynthetic organisms capture solar energy and store it in sugars Energy stored in sugars must be converted to molecular energy (in the form of ATP) for use in energy-requiring reactions Most eukaryotes and some bacteria breakdown carbohydrates via aerobic respiration

Cycle of Photosynthesis and Aerobic Respiration energy S Y N T H O E T S O I S H P CO2 H2O sugar O2 Figure 7.2 The global connection between photosynthesis and aerobic respiration. note the cycling of materials, and the one-way flow of energy N A O E I R T O A B I C I R R E S P energy

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

Aerobic Respiration vs. Anaerobic Fermentation 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 Fermentation No O2 Aerobic Resp. O2 Present Glycolysis

Comparison of Aerobic Respiration and Fermentation cytoplasm ATP GLYCOLYSIS cytoplasm ATP GLYCOLYSIS mitochondrion KREBS CYCLE ATP additional reactions in cytoplasm ATP ATP Figure 7.3 Comparison of aerobic respiration and fermentation. ATP ELECTRON TRANSFER PHOSPHORYLATION B Fermentation A Aerobic respiration.

7.3 Glycolysis—Sugar Breakdown Begins Glycolysis begins the sugar breakdown pathway in both aerobic respiration and fermentation Occurs in cytoplasm of cells Requires initial investment of 2 ATP molecules Produces 4 ATP total, for a net yield of 2 ATP

Glycolysis Stage 1: Energy Investment Stage Cell uses ATP to phosphorylate compounds of glucose Stage 2: Energy Payoff Stage Two 3-C compounds oxidized For each glucose molecule: 2 Net ATP produced by substrate-level phosphorylation 2 molecules of NAD+NADH

Glycolysis – ATP-Requiring Steps 1. An enzyme transfers a phosphate group from ATP to glucose, forming glucose-6-phosphate (hexokinase) glucose ADP 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). Two ATP have now been invested in the reactions. glucose-6-phosphate ADP fructose-1,6-bisphosphate Glycolysis ATP-Requiring Steps 1 An enzyme transfers a phosphate group from ATP to glucose, forming glucose-6-phosphate. (You learned about this enzyme, hexokinase, in Figure 5.10 and Section 5.4). 2 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). Two ATP have now been invested in the reactions. ATP-Generating Steps 3 An enzyme attaches a phosphate to each PGAL , so two PGA (phosphoglycerate) form. Two electrons and a hydrogen ion (not shown) from each PGAL are accepted by NAD+, so two NADH form. 4 An enzyme transfers a phosphate group from each PGA to ADP, forming two ATP and two intermediate molecules (PEP). The original energy investment of two ATP has now been recovered. 5 An enzyme transfers a phosphate group from each PEP to ADP, forming two more ATP and two molecules of pyruvate. 6 Summing up, glycolysis yields two NADH, two ATP (net), and two pyruvate for each glucose molecule. Depending on the type of cell and environmental conditions, the pyruvate may enter the second stage of aerobic respiration or it may be used in other ways, such as in fermentation. ATP Building Steps 2 PGAL 2 NAD+ An enzyme attaches a phosphate to each PGAL, so two PGA (phospho- glycerate) form. Two electrons and a hydrogen ion (not shown) from each PGAL are accepted by NAD+, so two NADH form. 2 coenzymes reduced

Glycolysis – ATP-Requiring Steps An enzyme transfers a phosphate group from each PGA to ADP, forming two ATP and two intermediate molecules (PEP). The original energy investment of two ATP has now been recovered. 2 PGA 2 ADP 2 ATP produced by substrate-level phosphorylation An enzyme transfers a phosphate group from each PEP to ADP, forming two more ATP and two molecules of pyruvate. 2 ADP Glycolysis ATP-Requiring Steps 1 An enzyme transfers a phosphate group from ATP to glucose, forming glucose-6-phosphate. (You learned about this enzyme, hexokinase, in Figure 5.10 and Section 5.4). 2 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). Two ATP have now been invested in the reactions. ATP-Generating Steps 3 An enzyme attaches a phosphate to each PGAL , so two PGA (phosphoglycerate) form. Two electrons and a hydrogen ion (not shown) from each PGAL are accepted by NAD+, so two NADH form. 4 An enzyme transfers a phosphate group from each PGA to ADP, forming two ATP and two intermediate molecules (PEP). The original energy investment of two ATP has now been recovered. 5 An enzyme transfers a phosphate group from each PEP to ADP, forming two more ATP and two molecules of pyruvate. 6 Summing up, glycolysis yields two NADH, two ATP (net), and two pyruvate for each glucose molecule. Depending on the type of cell and environmental conditions, the pyruvate may enter the second stage of aerobic respiration or it may be used in other ways, such as in fermentation. Summing up, glycolysis yields two NADH, two ATP (net), and two pyruvate for each glucose molecule. Depending on the type of cell and environmental conditions, the pyruvate may enter the second stage of aerobic respiration or it may be used in other ways, such as in fermentation. 2 ATP produced by substrate-level phosphorylation 2 pyruvate Net 2 ATP + 2 NADH to second stage of aerobic respiration or fermentation

Glycolysis Takes place in all cells of the body Yields 2 Net ATP Recycles NADH (2) Creates 2 Pyruvic Acid RBC’s rely solely on glycolysis for energy…WHY? Pyruvic Acid has 1 of 3 fates: Aerobic Respiration (in mitochondria) Fermentation (Lactic Acid or Alcoholic)

7.4 Second Stage of Aerobic Respiration The second stage of aerobic respiration completes the breakdown of glucose that began in glycolysis Occurs in mitochondria Includes two sets of reactions: acetyl-CoA formation and the Krebs cycle (each occurs twice in the breakdown of one glucose molecule)

Second Stage of Aerobic Respiration – In the Matrix cytoplasm outer membrane inner membrane The breakdown of 2 pyruvate to 6 CO2 yields 2 ATP and 10 reduced coenzymes (8 NADH, 2 FADH2). The coenzymes will carry their cargo of electrons and hydrogen ions to the third stage of aerobic respiration. matrix Figure 7.6 Animated The second stage of aerobic respiration, acetyl–CoA formation and the Krebs cycle, occurs inside mitochondria. Left, an inner membrane divides a mitochondrion’s interior into two fluid-filled compartments. Right, the second stage of aerobic respiration takes place in the mitochondrion’s innermost compartment, or matrix.

Acetyl-CoA Formation In the inner compartment of the mitochondrion, enzymes split pyruvate, forming acetyl-CoA and CO2 (which diffuses out of the cell) NADH is formed

The Krebs Cycle A sequence of enzyme-mediated reactions that break down 1 acetyl-CoA into 2 CO2 Oxaloacetate is used and regenerated 3 NADH and 1 FADH2 are formed 1 ATP is formed

Acetyl–CoA Formation and the Krebs Cycle An enzyme splits a pyruvate coenzyme A NAD+ 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. 1 The Krebs cycle starts as one carbon atom is transferred from acetyl–CoA tooxaloacetate. Citrate forms, and coenzyme A is regenerated. 2 The final steps of the Krebs cycle regenerate oxaloacetate. 8 A carbon atom is removed from an intermediate and leaves the cell as CO2. NAD+ combines with released hydrogen ions and electrons, forming NADH. 3 NAD+ combines with hydrogen ions and electrons, forming NADH. 7 Krebs Cycle Figure 7.7 Acetyl–CoA and the Krebs cycle. It takes two cycles of Krebs reactions to break down two pyruvate molecules that formed during glycolysis of one glucose molecule. After two cycles, all six carbons that entered glycolysis in one glucose molecule have left the cell, in six CO2. Electrons and hydrogen ions are released as each carbon is removed from the backbone of intermediate molecules; ten coenzymes will carry them to the third and final stage of aerobic respiration. Not all reactions are shown; Appendix V has more details. The coenzyme FAD combines with hydrogen ions and electrons, forming FADH2. 6 A carbon atom is removed from another intermediate and leaves the cell as CO2, and another NADH forms. Pyruvate’s three carbon atoms have now exited the cell, in CO2. 4 One ATP forms by substrate-level phosphorylation. 5 Stepped Art

Acetyl CoA & Krebs Cycle End of the road for sugar….. Products: NADH/FADH2/H+ (these products advance to the ETC) CO2 ATP

7.5 Aerobic Respiration’s Big Energy Payoff Many ATP are formed during the third and final stage of aerobic respiration Electron transfer phosphorylation (also known as the Electron Transport Chain) Occurs in mitochondria (using christae) Results in attachment of phosphate to ADP to form ATP

Electron Transfer Phosphorylation Coenzymes NADH and FADH2 donate electrons and H+ to electron transfer chains Active transport forms a H+ concentration gradient in the outer mitochondrial compartment H+ follows its gradient through ATP synthase, which attaches a phosphate to ADP …just like… Finally, oxygen accepts electrons and combines with H+, forming water (it’s here where 4% of oxygen gets over reduced and becomes a free radical )

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

7.6 Fermentation Glycolysis is the first stage of fermentation Forms 2 pyruvate, 2 NADH, and 2 ATP Pyruvate is converted to other molecules, but is not fully broken down to CO2 and water Regenerates NAD+ but does not produce ATP Provides enough energy for some single-celled anaerobic species

Two Fermentation Pathways – Alcoholic Fermentation Pyruvate is split into acetaldehyde and CO2 Acetaldehyde receives electrons and hydrogen from NADH, forming NAD+ and ethanol Carried out by single-celled organisms such as fungi (yeast) Used to make beer, wine, and bread

Alcoholic Fermentation

Two Fermentation Pathways – Lactate Fermentation Pyruvate receives electrons and hydrogen directly from NADH, forming NAD+ and lactate Carried out by beneficial bacteria Used to make yogurt Also carried out by animal white skeletal muscle cells Useful for quick, strenuous activities Does not support prolonged activity 3 min max

Lactate/ Lactic Acid Fermentation

7.7 Alternative Energy Sources in Food Aerobic respiration can produce ATP from the breakdown of complex carbohydrates, fats, and proteins As in glucose metabolism, many coenzymes are reduced The energy of the electrons the coenzymes carry ultimately drives the synthesis of ATP in electron transfer phosphorylation

Energy From Complex Carbohydrates Enzymes break starch and other complex carbohydrates down to monosaccharide subunits Monosaccharides are taken up by cells and converted to glucose-6-phosphate, which continues in glycolysis A high concentration of ATP causes glucose-6- phosphate to be diverted from glycolysis and into a pathway that forms glycogen

Complex Carbohydrates are Broken Down into Monosaccharides starch (a complex carbohydrate) glucose (a simple sugar) CH2OH HO O Figure 7.12 A variety of organic compounds from food can enter the reactions of aerobic respiration. A Complex carbohydrates are broken down to their monosaccharide subunits, which can enter glycolysis.

Most carbohydrates enter cellular respiration during glycolysis Most carbohydrates enter cellular respiration during glycolysis. In some cases, entering the pathway simply involves breaking a glucose polymer down into individual glucose molecules. For instance, the glucose polymer glycogen is made and stored in both liver and muscle cells in our bodies. If blood sugar levels drop, the glycogen will be broken down into phosphate-bearing glucose molecules, which can easily enter glycolysis.

Energy From Fats Enzymes cleave fats into glycerol and fatty acids Glycerol products enter glycolysis Fatty acids are converted to acetyl-CoA and enter the Krebs cycle Fatty acid breakdown yields more ATP per carbon atom than carbohydrates When blood glucose level is high, acetyl-CoA is diverted from the Krebs cycle and into a pathway that makes fatty acids

Fats are Broken Down by Separating the Glycerol Head and Fatty Acid Tails a triglyceride (fat) glycerol head fatty acid tails Figure 7.12 A variety of organic compounds from food can enter the reactions of aerobic respiration. B Fats are broken down by separating the glycerol head from the fatty acid tails. The fatty acids are converted to acetyl-CoA, and the glycerol is converted to PGAL.

Energy From Proteins “When you eat proteins in food, your body has to break them down into amino acids before they can be used by your cells. Most of the time, amino acids are recycled and used to make new proteins, not oxidized for fuel. However, if there are more amino acids than the body needs, or if cells are starving, some amino acids will broken down for energy via cellular respiration”—Khan Academy

Energy from Proteins Enzymes split dietary proteins into amino acid subunits, which are used to build proteins or other molecules (or energy?? WHEN?) First the amino group is removed and converted into ammonia (NH3), a waste product eliminated in urine Once deaminated, different amino acids enter the cellular respiration pathways at different stages Acetyl–CoA, pyruvate, or an intermediate of the Krebs cycle forms, depending on the amino acid

Amino Acids Are Converted alanine (an amino acid) pyruvate Figure 7.12 A variety of organic compounds from food can enter the reactions of aerobic respiration. C Amino acids are converted to acetyl-CoA, pyruvate, or an intermediate of the Krebs cycle.

Points to Ponder Why are so many diseases attributed to defective mitochondria? What is “metabolic water”? What happens to lactate produced during periods of intense muscle activity? Why is it important that the lactate is broken down quickly?