Cellular Respiration PDF

 CELLULAR RESPIRATION  CELLULAR RESPIRATION Cellular respiration is the process by which cells derive energy from glucose. The chemical reaction for cellular respiration involves glucose and oxygen as inputs, and produces carbon dioxide, water, and energy (ATP) as outputs.  CELLULAR RESPI...

 CELLULAR RESPIRATION  CELLULAR RESPIRATION Cellular respiration is the process by which cells derive energy from glucose. The chemical reaction for cellular respiration involves glucose and oxygen as inputs, and produces carbon dioxide, water, and energy (ATP) as outputs.  CELLULAR RESPIRATION Cellular respiration is a metabolic pathway that uses glucose to produce adenosine triphosphate (ATP), an organic compound the body can use for energy. One molecule of glucose can produce a net of 32-36 ATP  FATES OF PYRUVATE FATES OF PYRUVATE The presence or absence of oxygen determines the fates of the pyruvate produced in glycolysis. When plenty of oxygen is available (aerobic conditions), pyruvate is first converted to acetyl-CoA. However, in the absence of oxygen (that is, under anaerobic conditions), the fate of pyruvate is different in different organisms. In vertebrates, pyruvate is converted to lactate, while other organisms, such as yeast, convert pyruvate to ethanol and carbon dioxide. FATES OF PYRUVATE In the presence of oxygen, pyruvate is converted to acetyl- CoA which then enters the citric acid cycle to produce more ATP. In the absence of oxygen, pyruvate is converted to lactate, and NADH is re-oxidized to NAD+. In alcoholic fermentation, pyruvic acid changes to alcohol and carbon dioxide. FATES OF PYRUVATE If oxygen is available, aerobic respiration will go forward. The pyruvate molecules produced at the end of glycolysis are transported into mitochondria. In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo changes. FATES OF PYRUVATE In the mitochondrial matrix, pyruvate will be transformed into a two-carbon compound by removing a molecule of carbon dioxide. This also produces NADH. The resulting compound is called acetyl-CoA ANAEROBIC RESPIRATION OR FERMENTATION Fermentation is the process of producing ATP in the absence of oxygen. Glycolysis breaks a glucose molecule into two pyruvate molecules, producing a net gain of two ATP and two NADH molecules. Lactic acid fermentation is the type of anaerobic respiration carried out by yogurt bacteria (Lactobacillus and others) and by your own muscle cells when you exercise. LACTIC ACID FERMENTATION ALCOHOLIC FERMENTATION Alcoholic fermentation consists of pyruvate being first converted into acetaldehyde by the enzyme pyruvate decarboxylase and releasing CO2. In the second step acetaldehyde is reduced to ethanol using alcohol dehydrogenase and producing NAD+ in the process. ALCOHOLIC FERMENTATION SUMMARY In the presence of oxygen, pyruvate is converted to acetyl-CoA which then enters the citric acid cycle to produce more ATP. In the absence of oxygen, pyruvate is converted to lactate, and NADH is re-oxidized to NAD+. In alcoholic fermentation, pyruvic acid changes to alcohol and carbon dioxide. This type of fermentation is carried out by yeasts and some bacteria. CYTOPLASM GLYCOLYSIS NADPH (NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE HYDROGEN) A coenzyme that acts as an electron donor in anabolic reactions, like biosynthesis and antioxidant defense. Purpose: Supplies reducing power for building molecules and detoxifying reactive oxygen species. NAD⁺ (NICOTINAMIDE ADENINE DINUCLEOTIDE) A coenzyme involved in redox reactions, acting as an electron carrier during cellular respiration. Purpose: Helps produce ATP by transferring electrons in energy- generating pathways. GLYCOLYSIS Glycolysis is the metabolic pathway by which glucose (a C6 molecule) is converted into two molecules of pyruvate (a C3 molecule), chemical energy in the form of ATP is produced, and NADH-reduced coenzymes are produced. It is a linear rather than cyclic pathway that functions in almost all cells. GLYCOLYSIS The conversion of glucose to pyruvate is an oxidation process in which no molecular oxygen is utilized. The oxidizing agent is the coenzyme NAD+. Metabolic pathways in which molecular oxygen is not a participant are called anaerobic pathways. Pathways that require molecular oxygen are called aerobic pathways. Glycolysis is an anaerobic pathway. WHERE GLYCOLYSIS OCCURS Glycolysis occurs in the cytoplasm, where all the necessary enzymes are located. This fluid environment allows for efficient breakdown of glucose into pyruvate, generating ATP and NADH. The cytosol's accessibility to glucose enables glycolysis to respond quickly to the cell's energy needs. GLYCOLYSIS NET EQUATION CYTOPLASM STEPS OF GLYCOLYSIS There are two stages in the overall process, a six-carbon stage (STEPS 1- 3) and a three-carbon stage (STEPS 4-10). All of the enzymes needed for glycolysis takes place. Details of the individual steps within the glycolysis pathway will now be considered. STEPS 1-3: SIX-CARBON STAGE (INVESTMENT PHASE) STEPS 1-3: SIX-CARBON STAGE The six-carbon stage of glycolysis is an energy- consuming stage. The energy release associated with the conversion of two ATP molecules to two ADP molecules is used to transform monosaccharides into monosaccharide phosphates. The intermediates of the six-carbon stage of glycolysis are all either glucose or fructose derivatives in which phosphate groups are present.  STEP 1: PHOSPHORYLATION USING ATP : FORMATION OF GLUCOSE 6-PHOSPHATE  STEP 1 The enzyme hexokinase phosphorylates adds a phosphate group to glucose in a cell's cytoplasm. In the process, a phosphate group from ATP is transferred to glucose producing glucose 6- phosphate or G6P. One molecule of ATP is consumed during this phase.  STEP 1: PHOSPHORYLATION USING ATP : FORMATION OF GLUCOSE 6-PHOSPHATE STEP 2: ISOMERIZATION: FORMATION OF FRUCTOSE 6 - PHOSPATE  STEP 2 The enzyme phosphoglucomutase isomerizes G6P into its isomerfructose 6-phosphate or F6P. Isomers have the same molecular formula as each other but different atomic arrangements.  STEP 2 The net result of this change is that carbon 1 of glucose is no longer part of the right structure. Glucose, an aldose, forms a six-membered ring, and fructose, a ketose, forms a five-membered ring; both sugars, however, contain six carbon atoms. STEP 2: ISOMERIZATION: FORMATION OF FRUCTOSE 6 - PHOSPATE STEP 3: PHOSPHORYLATION USING ATP: FORMATION OF FRUCTOSE 1,6 - BIPHOSPHATE  STEP 3 The kinase phosphofructokinase uses another ATP molecule to transfer a phosphate group to F6P in order to form fructose 1,6-bisphosphate or FBP. Two ATP molecules have been used so far.  STEP 3 This step, like Step 1, is a phosphorylation reaction and therefore requires the expenditure of energy. ATP is the source of the phosphate and the energy. The enzyme involved, phosphofructokinase, is another enzyme that requires Mg2+ ion for its activity. The fructose molecule now contains two phosphate groups.  STEP 3: PHOSPHORYLATION USING ATP: FORMATION OF FRUCTOSE 1,6 - BIPHOSPHATE STEPS 4-10: THREE CARBON STAGE OF GLYOCLYSIS STEPS 4-10: THREE CARBON STAGE OF GLYOCLYSIS The three -carbon stage of glycolysis is an energy-generating stage rather than an energy-consuming stage. All of the intermediates in this stage are C3-Phosphates, two of which are high-energy phosphate species. Loss of a phosphate from these high- energy species affects the conversion of ADP molecules to ATP molecules. STEP 4: CLEAVAGE: FORMATION OF TWO TRIOSE PHOSPHATES  STEP 4 The enzyme aldolase splits fructose 1,6-bisphosphate into a ketone and an aldehyde molecule. These sugars, dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP), are isomers of each other.  STEP 4 In this step, the reacting C6 species is split into two C3 (triose) species. Because fructose 1,6-biphosphate, the molecule being split, is asymmetrical, the two trioses produced are not identical. One product is dihydroxyacetone phosphate, and the other is glyceraldehyde 3-phosphate. Aldolase is the enzyme that catalyzes this reaction. STEP 4: CLEAVAGE: FORMATION OF TWO TRIOSE PHOSPHATES STEP 5: ISOMERIZATION: FORMATION OF GLYCERALDEHYDE 3 - PHOSPHATE  STEP 5 The enzyme triose- phosphate isomerase rapidly converts DHAP (Dihydroxyacetone phosphate) into GAP (these isomers can inter-convert). GAP is the substrate needed for the next step of glycolysis.  STEP 5 Dihydroxyacetone phosphate (a ketose) and glyceraldehyde 3-phosphate (an aldose) are isomers, and the isomerization process from ketose to aldose is catalyzed by the enzyme triosephosphate isomerase. STEP 5: ISOMERIZATION: FORMATION OF GLYCERALDEHYDE 3 - PHOSPHATE STEP 6: OXIDATION AND PHOSPHORYLATION USING PI: FORMATION OF 1, 3 - BISPHOSPHO- GLYCERATE  STEP 6 The enzyme glyceraldehyde 3- phosphate dehydrogenase(GAPDH) serves two functions in this reaction. First, it dehydrogenates GAP by transferring one of its hydrogen (H⁺) molecules to the oxidizing agentnicotinamide adenine dinucleotide (NAD⁺) to form NADH + H⁺.  STEP 6 Next, GAPDH adds a phosphate from the cytosol to the oxidized GAP to form 1,3- bisphosphoglycerate (BPG). Both molecules of GAP produced in the previous step undergo this process of dehydrogenation and phosphorylation. STEP 6: OXIDATION AND PHOSPHORYLATION USING PI: FORMATION OF 1, 3 - BISPHOSPHO-GLYCERATE  STEP 7: PHOSPHORYLATION OF ADP: FORMATION OF 3-PHOSPHOGLYCERATE  STEP 7 The enzyme phosphoglycerokinase transfers a phosphate from BPG to a molecule of ADP to form ATP. This happens to each molecule of BPG. This reaction yields two 3-phosphoglycerate (3 PGA) molecules and two ATP molecules. STEP 7: PHOSPHORYLATION OF ADP: FORMATION OF 3-PHOSPHOGLYCERATE STEP 8: ISOMERIZATION: FORMATION OF 2-PHOSPHOGLYCERATE  STEP 8 The enzyme phosphoglyceromutase relocates the P of the two 3 PGA molecules from the third to the second carbon to form two 2- phosphoglycerate (2 PGA) molecules.  STEP 8 In this isomerization step, the phosphate group of 3- phosphoglycerate is moved from carbon 3 to carbon 2. The enzyme phosphoglyceromutase catalyzes the exchange of the phosphate group between the two carbons. STEP 8: ISOMERIZATION: FORMATION OF 2- PHOSPHOGLYCERATE STEP 9: DEHYDRATION: FORMATION OF PHOSPHOENOLPYRUVATE  STEP 9 The enzyme enolase removes a molecule of water from 2- phosphoglycerate to form phosphoenolpyruvate (PEP). This happens for each molecule of 2 PGA from Step 8. STEP 9: DEHYDRATION: FORMATION OF PHOSPHOENOLPYRUVATE STEP 10: PHOSPHORYLATION OF ADP: FORMATION OF PYRUVATE STEP 10 The enzyme pyruvate kinase transfers a P from PEP to ADP to form pyruvate and ATP. This happens for each molecule of PEP. This reaction yields two molecules of pyruvate and two ATP molecules. STEP 10: PHOSPHORYLATION OF ADP: FORMATION OF PYRUVATE ATP molecules are involved in Steps 1, 3, 7, and 10 of glycolysis. Considering these steps collectively shows that there is a net gain of two ATP molecules for every glucose molecule converted into two pyruvates. Though useful, this is a small amount of ATP compared to that generated in oxidative phosphorylation. ATP Used: 2 ATP are used in the early stages of glycolysis (in the energy investment phase), where ATP is consumed to phosphorylate glucose and fructose-6-phosphate. ATP Produced: 4 ATP are produced in the later stages of glycolysis (in the energy payoff phase), where two molecules of 1,3- bisphosphoglycerate and phosphoenolpyruvate each generate ATP through substrate-level phosphorylation. Net ATP: The net gain is 2 ATP, as 4 ATP are produced but 2 are consumed in the initial steps. Thus, glycolysis results in a net production of 2 ATP per glucose molecule. MITOCHONDRIAL MATRIX KREBS CYCLE CITRIC ACID CYCLE (KREBS CYCLE) The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, produces several key molecules for cellular energy production. CITRIC ACID CYCLE (KREBS CYCLE) The citric acid cycle is the series of biochemical reactions in which the acetyl portion of acetyl/CoA is oxidized to carbon dioxide and the reduced coenzymes FADH, and NADH are produced. This cycle, stage 3 of biochemical energy production, gets its name from the first intermediate product in the cycle, citric acid. CITRIC ACID CYCLE (KREBS CYCLE) It is also known as the Krebs cycle, after its discoverer Hans Adolf Krebs, and as the tricarboxylic acid cycle, in reference to the three carboxylate groups present in citric acid. The chemical reactions of the citric acid cycle take place in the mitochondrial matrix where the needed enzymes are found, except the Succinate dehydrogenase reaction that involves FAD. CITRIC ACID CYCLE (KREBS CYCLE) The enzyme that catalyzes this reaction is an integral part of the inner mitochondrial membrane. The individual steps of the cycle are now considered in detail. Oxidation, which produces NADH or FADH, is encountered in four of the eight steps, and decarboxylation, wherein a carbon chain is shortened by the removal of a carbon atom as a CO, molecules, is encountered in two of the eight steps.  ACRONYMS ATP - Adenosine Triphosphate: A high-energy molecule used by cells as an energy source. GTP - Guanosine Triphosphate: An energy-rich molecule similar to ATP that can be converted to ATP. NADH - Nicotinamide Adenine Dinucleotide (reduced form): An electron carrier that stores energy used to produce ATP in the electron transport chain.  FADH₂ - Flavin Adenine Dinucleotide (reduced form): Another electron carrier that donates electrons to the electron transport chain, producing ATP. CoA - Coenzyme A: A molecule that carries acyl groups such as acetyl groups into the Krebs cycle. STEPS OF KREBS CYCLE STEP 1: FORMATION OF CITRATE  STEP 1: FORMATION OF CITRATE Acetyl CoA, Which carries the two-carbon degradation product of carbohydrates, fats, and proteins, enters the cycle by combining with the four-carbon keto dicarboxylate species oxaloacetate. This results in the transfer of the acetyl group from coenzyme A to oxaloacetate, producing the C₆ citrate species and free coenzyme A.  STEP 1: FORMATION OF CITRATE There are two parts to the reaction: (1) the condensation of acetyl CoA and oxaloacetate to form citryl CoA, a process catalyzed by the enzyme citrate synthase and (2) hydrolysis of the thioester bond in citryl CoA to produce CoA —SH and citrate, also catalyzed by the enzyme citrate synthase. STEP 1: FORMATION OF CITRATE STEP 2: FORMATION OF ISOCITRATE  STEP 2: FORMATION OF ISOCITRATE Citrate is converted to its less symmetrical isomer isocitrate in an isomerization process that involves a dehydration followed by a hydration, both catalyzed by the enzyme aconitase. The net result of these reactions is that the -OH group from citrate is moved to a different carbon atom.  STEP 2: FORMATION OF ISOCITRATE Citrate is an achiral compound, and isocitrate is a chiral compound with two chiral centers (four stereoisomers possible). Aconitase produces only one of the four stereoisomers isocitrate  STEP 2: FORMATION OF ISOCITRATE Citrate is a tertiary alcohol and isocitrate a secondary alcohol. Tertiary alcohols are not readily oxidized; secondary alcohols are easier to oxidize. The next step in the cycle involves oxidation. STEP 2: FORMATION OF ISOCITRATE  STEP 3: OXIDATION OF ISOCITRATE AND FORMATION OF CO₂  STEP 3: OXIDATION OF ISOCITRATE AND FORMATION OF CO₂ This step involves oxidation-reduction (the first of four redox reactions in the citric acid cycle) and decarboxylation. The reactants are a NAD molecule and isocitrate. The reaction, catalyzed by isocitrate dehydrogenase, is complex: (1) Isocitrate is oxidized to a ketone (oxalosuccinate) by NAD⁺, releasing two hydrogens  STEP 3: OXIDATION OF ISOCITRATE AND FORMATION OF CO₂ (2) One hydrogen and two electrons are transferred to NAD⁺ to form NADH; the remaining hydrogen ion (H⁺) is released. (3) The oxalosuccinate remains bound to the enzyme and undergoes decarboxylation (loses COz), which produces the C, a-ketoglutarate (a keto dicarboxylate species).  STEP 3: OXIDATION OF ISOCITRATE AND FORMATION OF CO₂ STEP 4: OXIDATION OF A- KETOGLUTARATE AND FORMATION OF CO₂  STEP 4: OXIDATION OF A- KETOGLUTARATE AND FORMATION OF CO₂ This second redox reaction of the cycle involves one molecule each NAD⁺, CoA-SH, and a-ketoglutarate. The catalyst is a three enzyme system called the a- ketoglutarate dehydrogenase complex. The B vitamin Thiamin, in the form of TPP, is part of the enzyme complex, as is Mg²⁺ ion. As in step 3, both oxidation and decarboxylation occur. There are three products: CO₂, NADH, and the C₄ species succinyl CoA. STEP 4: OXIDATION OF A- KETOGLUTARATE AND FORMATION OF CO₂  STEP 5: THIOESTER BOND CLEAVAGE IN SUCCINYL COA AND PHOSPHORYLATION OF GDP  STEP 5: THIOESTER BOND CLEAVAGE IN SUCCINYL COA AND PHOSPHORYLATION OF GDP Two reactant molecules are involved in this step: a P, CHPO, and a GDP (similar to ADP). The entire reaction is catalyzed by the enzyme succinyl/-CoA synthetase. For purposes of understanding the Structural changes that occur, the reaction can be considered to occur in two steps.  STEP 5: THIOESTER BOND CLEAVAGE IN SUCCINYL COA AND PHOSPHORYLATION OF GDP STEP 6: OXIDATION OF SUCCINATE  STEP 6: OXIDATION OF SUCCINATE This is the third redox reaction of the cycle. The enzyme involved is succinate dehydrogenase, and the oxidizing agent is FAD rather than NAD*. two hydrogen atoms are removed from the succinate to produce fumarate, a C₄ species with a trans doubles bond. FAD is reduced to FAHD₂ in the process. STEP 6: OXIDATION OF SUCCINATE STEP 7: HYDRATION OF FUMARATE  STEP 7: HYDRATION OF FUMARATE The enzyme fumarase catalyzes the addition of water to the double bond of fumarate. The enzyme is stereospecific, so only the L isomer of the product malate is produced. STEP 7: HYDRATION OF FUMARATE STEP 8: OXIDATION OF L- MALATE TO REGENERATE OXALOACETATE  STEP 8: OXIDATION OF L- MALATE TO REGENERATE OXALOACETATE In the fourth oxidation-reduction reaction of the cycle, a molecule of NAD* reacts with malate, picking up two hydrogen atoms with their associated energy to form NADH + H*. The needed enzyme is malate dehydrogenase. STEP 8: OXIDATION OF L- MALATE TO REGENERATE OXALOACETATE An overall summary equation for the citric acid cycle is obtained by adding together the individual reactions of the cycle: IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 1. The "fuel" for the cycle is acetyl CoA, obtained from the breakdown of car- bohydrates, fats, and proteins. IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 2. Four of the cycle reactions involve oxidation and reduction. The oxidizing agent is either (three times) or FAD once). The operation of the cycle depends on the availability of these oxidizing agents. IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 3. In redox reactions, NAD+ is the oxidizing agent when a carbon oxygen double bond is formed; FAD is the oxidizing agent when a carbon carbon double bond is formed. IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 4. The three NADH and one FADH, that are formed during the cycle carry electrons and H⁺ to the electron transport chain through which ATP is synthesized. IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 5. Two carbon atoms enter the cycle as the acetyl unit of acetyl CoA, and two carbon atoms leave the cycle as two molecules of CO2. The carbon atoms that enter and leave are not the same ones. The carbon atoms that leave during one turn of the cycle are carbon atoms that entered during the previous turn of the cycle. IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 6. Four B vitamins are necessary for the proper functioning of the cycle, riboflavin I both FAD and the a-ketoglutarate dehydrogenase complex), nicotinamide (in NAD⁺). pantothenic acid (in Co.A —SH), and thiamine (in the a- ketoglutarate dehydrogenase complex). IMPORTANT FEATURES OF THE CYCLE INCLUDE THE FOLLOWING: 7. One high-energy GTP (Guanosine-5'- triphosphate) molecule is produced by phosphorylation. The Chemistry at a Glance feature on the next page gives a detailed diagrammatic summary of the reactions that occur in the citric acid cycle. PRODUCTS AT THE END OF KREBS CYCLE The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, produces several key molecules for cellular energy production. PRODUCTS AT THE END OF KREBS CYCLE It produces two molecules of carbon, three molecules of NADH, one molecule of FADH2 and one molecule of ATP or GTP. ENZYMES OF THE KREBS CYCLE:  Citrate Synthase: Converts acetyl-CoA and oxaloacetate to citrate. Aconitase Cis- Aconitase: Converts citrate to isocitrate via cis-aconitate. Isocitrate Dehydrogenase: Converts isocitrate to α-ketoglutarate, producing NADH and releasing CO₂.  α-Ketoglutarate Dehydrogenase: Converts α-ketoglutarate to succinyl-CoA, producing NADH and releasing CO₂. Succinyl-CoA Synthetase: Converts succinyl-CoA to succinate, generating GTP (or ATP). Succinate Dehydrogenase: Converts succinate to fumarate, producing FADH₂. Fumarase (Fumarate Hydratase)  Fumarase (Fumarate Hydratase): Converts fumarate to malate. Oxaloacetate: dicarboxylic acid that plays a crucial role in various metabolic pathways, particularly in the citric acid cycle (Krebs cycle).