Cellular Respiration PDF

CELLULAR RESPIRATION Prepared by: Lenor M. Tunac MAED-BIO Objectives To describe the major features and chemical events in the 3 stages of cellular respiration; To account for the net ATP produced per stage; To describe anaerobic respiration and its significance in cellular respiration;...

CELLULAR RESPIRATION Prepared by: Lenor M. Tunac MAED-BIO Objectives To describe the major features and chemical events in the 3 stages of cellular respiration; To account for the net ATP produced per stage; To describe anaerobic respiration and its significance in cellular respiration; To differentiate anaerobic from aerobic respiration; To give examples of practical uses of aerobic and anaerobic cellular respiration. Glycolysis 4-4  Chemical Energy Transfer by ATP Glycolysis Occurs in cytoplasm Involves 10 enzymatically catalyzed reactions Glucose (and other 6- carbon monosaccharides) is split into 2 molecules of pyruvic acid (3 carbons) Net of 2 ATP molecules formed 4-5 Glycolysis the first step in the breakdown of glucose to extract energy for cellular metabolism. does not use oxygen and is therefore anaerobic. takes place in the cytoplasm of both prokaryotic and Glycolysis The first part of the glycolysis pathway traps the glucose molecule in the cell and uses energy to modify it so that the six-carbon sugar molecule can be split evenly into the two three-carbon molecules. The second part of glycolysis extracts energy from the molecules and stores it in the form of ATP and NADH, the reduced form of NAD.  Chemical Energy Transfer by ATP Coenzyme Nicotinamide Adenine Dinucleotide (NAD+) NAD+ accepts a hydrogen ion and electrons removed from substrate molecules Converted to reduced form, NADH Carrier molecule that conveys high- energy electrons to the final electron transport chain for ATP production Glucose + 2 ADP + 2 Pi + NAD+ → 2 Pyruvic + 2 NADH + 2 ATP Acid 4-8 First Half of Glycolysis (Energy-Requiring Steps) Step 1. The first step in glycolysis is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars. Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6- phosphate, a more reactive form of glucose. This reaction prevents the phosphorylated glucose molecule from continuing to interact with the GLUT proteins, and it can no longer leave the cell because the negatively charged phosphate will not allow it to cross the hydrophobic interior of the plasma membrane. First Half of Glycolysis (Energy- Requiring Steps) Step 2. In the second step of glycolysis, an isomerase converts glucose-6- phosphate into one of its isomers, fructose-6-phosphate. An isomerase is an enzyme that catalyzes the conversion of a molecule into one of its isomers. (This change from phosphoglucose to phosphofructose allows the eventual split of the sugar into two three-carbon First Half of Glycolysis (Energy-Requiring Steps) Step 3. The third step is the phosphorylation of fructose-6- phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP molecule donates a high-energy phosphate to fructose-6-phosphate, producing fructose-1,6- bisphosphate. In this pathway, phosphofructokinase is a rate-limiting enzyme. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high. Thus, if there is “sufficient” ATP in the system, the pathway slows down. This is a type of end product inhibition, since ATP is the end product of glucose catabolism. First Half of Glycolysis (Energy- Requiring Steps) Step 4. The newly added high-energy phosphates further destabilize fructose- 1,6-bisphosphate. The fourth step in glycolysis employs an enzyme, aldolase, to cleave 1,6-bisphosphate into two three-carbon isomers: dihydroxyacetone-phosphate First Half of Glycolysis (Energy- Requiring Steps) Step 5. In the fifth step, an isomerase transforms the dihydroxyacetone-phosphate into its isomer, glyceraldehyde-3-phosphate. Thus, the pathway will continue with two molecules of a single isomer. At this point in the pathway, there is a net investment of energy from two ATP molecules in the breakdown of one glucose molecule. The first half of glycolysis uses two ATP molecules in the phosphorylation of glucose, which is then split into two three-carbon molecules.  So far, glycolysis has cost the cell two Second Half of Glycolysis (Energy-Releasing Steps) ATP molecules and produced two small, three-carbon sugar molecules. Both of these molecules will proceed through the second half of the pathway, and sufficient energy will be extracted to pay back the two ATP molecules used as an initial investment and produce a profit for the cell of two additional ATP molecules and two even higher-energy NADH molecules. Second Half of Glycolysis (Energy-Releasing Steps) Step 6. The sixth step in glycolysis oxidizes the sugar (glyceraldehyde-3-phosphate), extracting high-energy electrons, which are picked up by the electron carrier NAD+, producing NADH. The sugar is then phosphorylated by the addition of a second phosphate group, producing 1,3-bisphosphoglycerate. Note that the second phosphate group does not require another ATP molecule.  Second Half of Glycolysis (Energy-Releasing Steps) The second half of glycolysis involves phosphorylation without ATP investment (step 6) and produces two NADH and four ATP molecules per glucose. Step 7. In the seventh step, catalyzed by phosphoglycerate kinase (an enzyme named for the reverse reaction), 1,3- bisphosphoglycerate donates a high-energy phosphate to ADP, forming one molecule of ATP. (This is an example of substrate- level phosphorylation.) A carbonyl group on the 1,3- bisphosphoglycerate is oxidized Step 8. In the eighth step, the remaining phosphate group in 3-phosphoglycerate moves from the third carbon to the second carbon, producing 2- phosphoglycerate (an isomer of 3-phosphoglycerate). The enzyme catalyzing this step is a mutase (isomerase). Step 9. Enolase catalyzes the ninth step. This enzyme causes 2-phosphoglycerate to lose water from its structure; this is a dehydration reaction, resulting in the formation of a double bond that increases the potential energy in the remaining phosphate bond and produces phosphoenolpyruvate (PEP). Step 10. The last step in glycolysis is catalyzed by the enzyme pyruvate kinase (the enzyme in this case is named for the reverse reaction of pyruvate’s conversion into PEP) and results in the production of a second ATP molecule by substrate-level phosphorylation and the compound pyruvic acid (or its salt form, pyruvate). Many enzymes in enzymatic pathways are named for the reverse reactions, since the enzyme can catalyze both forward and reverse reactions (these may have been described initially by the reverse reaction that takes place in vitro, under non-physiological conditions). Glycolysis starts with glucose Outcomes of Glycolysis and ends with two pyruvate molecules, a total of four ATP molecules and two molecules of NADH. Two ATP molecules were used in the first half of the pathway to prepare the six- carbon ring for cleavage, so the cell has a net gain of two ATP molecules and 2 NADH molecules for its use. If the cell cannot catabolize the pyruvate molecules further, it will harvest only two ATP molecules from one molecule of glucose. Mature mammalian red blood cells are not capable of aerobic respiration—the process in which organisms convert energy in the presence of oxygen—and glycolysis is their sole source of ATP. If glycolysis is interrupted, these cells lose their ability to maintain their sodium-potassium pumps, and eventually, they die The last step in glycolysis will not occur if pyruvate kinase, the enzyme that catalyzes the formation of pyruvate, is not available in sufficient quantities. In this situation, the entire glycolysis pathway will proceed, but only two ATP molecules will be made in the second half. Thus, pyruvate kinase is a rate-limiting Summary Glycolysis is the first pathway used in the breakdown of glucose to extract energy. It was probably one of the earliest metabolic pathways to evolve and is used by nearly all of the organisms on earth. Glycolysis consists of two ATP is invested in the process during this half to energize the separation. The second half of glycolysis extracts ATP and high- energy electrons from hydrogen atoms and attaches them to NAD+. Two ATP molecules are invested in the first half and four ATP molecules are formed by substrate phosphorylation during  Chemical Energy Transfer by ATP Acetyl-CoA: Strategic Intermediate in Respiration 2 pyruvic acid molecules (from glycolysis) enter mitochondrion Each is oxidized One carbon of each released as CO 2 Remaining two carbon residue condenses with coenzyme A (CoA) to form acetyl coenzyme A 1 NADH formed 4-27 Chemical Energy Transfer by ATP Acetyl CoA  Critically important compound  Oxidation in Krebs cycle provides energized electrons to generate ATP  Crucial intermediate in lipid metabolism 4-28  Oxidation of Pyruvate and the Citric Acid Cycle Objectives: Explain how a circular pathway, such as the citric acid cycle, fundamentally differs from a linear pathway, such as glycolysis Describe how pyruvate, the product of glycolysis, is prepared for entry into the citric acid cycle Pyruvate to the mitochondria, the site for cellular respiration Pyruvate will be transformed into an acetyl group that will be picked up and activated by a carrier compound called coenzyme A (CoA). The resulting compound is called acetyl CoA. It deliver the acetyl group derived from pyruvate to the next stage of the pathway in glucose catabolism. CoA is made from vitamin B5, pantothenic acid. Breakdown of Pyruvate 3-step processes in converting PA to acetyl Co- A Acetyl CoA In the presence of oxygen, acetyl CoA delivers its acetyl group to a four- carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups Citric Acid Cycle 4-36 Citric Acid Cycle Unlike glycolysis, the citric acid cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step. Citric Acid Cycle The eight steps of the cycle are a series of redox, dehydration, hydration, and decarboxylation reactions that produce two carbon dioxide molecules, one GTP/ATP, and reduced forms of NADH and FADH2 (Figure 7.3.2).  Each turn of the cycle forms three NADH molecules and one FADH2molecule. These carriers will connect with the last portion of aerobic respiration to produce ATP molecules. Citric Acid Cycle This is considered an aerobic pathway because the NADH and FADH2 produced must transfer their electrons to the next pathway in the system, which will use oxygen. If this transfer does not occur, the oxidation steps of the citric acid cycle also do not occur. Note that the citric acid cycle produces very little ATP directly and does not directly consume oxygen. Step 1. A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide into the surrounding medium. The result of this step is a two-carbon hydroxyethyl group bound to the enzyme (pyruvate dehydrogenase). This is the first of the six carbons from the original glucose molecule to be removed. This step proceeds twice (remember: there are two pyruvate molecules produced at the end of glycolysis) for every molecule of glucose metabolized; thus, two of the six carbons will have been removed at the end of both steps. Step 2. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH. The high-energy electrons from NADH will be used later to generate ATP. Step 3. The enzyme- bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA. Note that during the second stage of glucose metabolism, whenever a carbon atom is removed, it is bound to two oxygen atoms, producing carbon dioxide, one of the major end products of cellular respiration. Acetyl CoA to CO2 In the presence of oxygen, acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups; this pathway will harvest the remainder of the extractable energy from what began as a glucose molecule. This single pathway is called by different names: the citric acid cycle (for the first intermediate formed—citric acid, or citrate—when acetate joins to the oxaloacetate), the TCA cycle (since citric acid or citrate and isocitrate are tricarboxylic acids), and the Krebs cycle, after Hans Krebs, who first identified the steps in the pathway in the 1930s in pigeon flight muscles. Citric Acid Cycle Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of mitochondria. Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion. Unlike glycolysis, the citric acid cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step. Citric Acid Cycle This is considered an aerobic pathway because the NADH and FADH2 produced must transfer their electrons to the next pathway in the system, which will use oxygen. If this transfer does not occur, the oxidation steps of the citric acid cycle also do not occur. Note that the citric acid cycle produces very little ATP directly and does not directly consume oxygen.  Chemical Energy Transfer by ATP Krebs Cycle: Oxidation of Acetyl-CoA Oxidation of Acetyl-CoA takes place in matrix of the mitochondria Acetyl-CoA Condenses with 4-carbon acid (oxaloacetic acid) Through a cyclic series of reactions CoA is released Remaining two carbons from the acetyl group are released as CO2 Oxaloacetic acid is regenerated 4-47 Chemical Energy Transfer by ATP  Six additional NADH formed  Two FADH2 formed  Flavin Adenine Dinucleotide (FAD)  Electron acceptor  Reduced form FADH 2  Two ATP molecules formed by substrate level phosphorylation.  Each turn of the cycle forms three NADH molecules and one FADH2molecule. These carriers will connect with the last portion of aerobic respiration to produce ATP molecules. 4-48 4-49  Chemical Energy Transfer by ATP Electron Transport Chain Involves the transfer of electrons from NADH and FADH2 to molecular oxygen Involves an elaborate electron transport chain embedded in the inner mitochondrial membrane Carrier molecules in chain are large transmembrane protein-based complexes Accept and release electrons in downhill fashion Energy is released with each transfer 4-50 Chemical Energy Transfer by ATP Energy is used to transport H+ into the innermembrane space Creates a H+ gradient H+ gradient drives synthesis of ATP by chemiosmotic coupling NADH and FADH donate electrons 2 which are shuttled down the electron transport chain Movement of electrons activates a proton pump 4-51 Chemical Energy Transfer by ATP H+ are pumped into the space between the inner and outer mitochondrial membrane creating a H+ gradient H+ ions diffuse back into the matrix through special ATP-forming protein complexes Flow of H+ powers ATP synthesis 4-52 4-53 Chemical Energy Transfer by ATP Oxidation of 1 NADH yields 3 ATP molecules Oxidation of 1 FADH yields 2 ATP molecules This method of energy capture is called oxidative phosphorylation  Formation of high-energy phosphate is coupled to oxygen consumption 4-54  Chemical Energy Transfer by ATP Efficiency of Oxidative Phosphorylation ATP yield from the complete oxidation of glucose: Glucose + 2 ATP + 36 ADP + 36 P + 6 O 2 → 6 CO2 + 2 ADP + 36 ATP + 6 H20 4-55  Chemical Energy Transfer by ATP Yield of 36 ATP is a theoretical maximum Overall efficiency of aerobic oxidation of glucose: 36% Efficiency of human-designed machines: 5% to 10% 4-56 4-57  Chemical Energy Transfer by ATP Anaerobic Glycolysis: Generating ATP Without Oxygen In absence of molecular oxygen Further oxidation of pyruvic acid cannot occur Krebs cycle and electron transport chain are oxygen requiring pathways 4-58 Chemical Energy Transfer by ATP NADH reduces pyruvic acid to lactic acid Pyruvic acid serves as final electron acceptor Alcoholic fermentation (yeast) NADH reduces pyruvic acid to ethanol 4-59  Chemical Energy Transfer by ATP Anaerobic glycolysis Only 1/18 as efficient as aerobic metabolism 4-60 4-61 Repeat viewing the power point together with the materials I gave until you are familiar with the process. Good luck ! Thank you for 1 semester of challenging interactions with everyone!!