Metabolic Pathways and Energy Production PDF

Metabolic Pathways and Energy Production BBIO109 - Biochemistry Prepared by: John Dale Mateo  Learning Objectives Explain the process of catabolism, the structure of ATP, and the role of ATP Describe the components and functions of the coenzymes NAD+, NADP+, FAD...

Metabolic Pathways and Energy Production BBIO109 - Biochemistry Prepared by: John Dale Mateo  Learning Objectives Explain the process of catabolism, the structure of ATP, and the role of ATP Describe the components and functions of the coenzymes NAD+, NADP+, FAD, and coenzyme A Explain the process of glycolysis, citric acid cycle, and electron- transport chain. Produce an audio-visual presentation that show the metabolic pathways METABOLISM AND ATP ENERGY  METABOLISM AND ATP ENERGY The term metabolism refers to all the chemical reactions that provide energy and the substances required for continued cell growth. There are two types of metabolic reactions: catabolic and anabolic.  METABOLISM AND ATP ENERGY In catabolic reactions, complex molecules are broken down to simpler ones with an accompanying release of energy. Anabolic reactions utilize energy available in the cell to build large molecules from simple ones.  ATP and ENERGY In our cells, the energy released from the oxidation of the food we eat is stored in the form of a “high-energy” compound called adenosine triphosphate (ATP).  ATP and ENERGY When ATP undergoes hydrolysis, the products are adenosine diphosphate (ADP), a phosphate group abbreviated as 𝑃𝑖 and energy of 7.3 kcal per mole of ATP. We can write this reaction as: The ADP can also hydrolyze to form adenosine monophosphate (AMP) and an inorganic phosphate (𝑃𝑖 )  ATP and ENERGY In a cell that is doing work (anabolic processes), 1–2 million ATP molecules may be hydrolyzed in one second. When we take in food, the resulting catabolic reactions provide energy to regenerate ATP in our cells. Then 7.3 kcal/mole is used to make ATP from ADP and 𝑃𝑖 DIGESTION OF FOODS  Digestion of Carbohydrates Enzymes produced in the salivary glands hydrolyze some of the α-glycosidic bonds in amylose and amylopectin, producing maltose, glucose, and smaller polysaccharides called dextrins, which contain three to eight glucose units. After swallowing, the partially digested starches enter the acidic environment of the stomach, where the low pH stops carbohydrate digestion. Digestion of Carbohydrates Small intestine enzymes hydrolyze dextrins to maltose and glucose. Mucosal cells (lining the small intestine) enzymes hydrolyze maltose, lactose, and sucrose. Monosaccharides are absorbed through intestinal wall into the bloodstream and carried to liver, where fructose and galactose are converted to glucose. Digestion of Fats In a process called emulsification, the bile salts break the fat globules into smaller droplets called micelles. Pancreatic enzymes hydrolyze triacylglycerols to monoacylglycerols and fatty acids. Digestion of Fats The chylomicrons transport the triacylglycerols to the cells of the heart, muscle, and adipose tissues. When energy is needed in the cells, enzymes hydrolyze the triacylglycerols to yield glycerol and fatty acids. Digestion of Proteins In stomach, HCl at pH 2 denatures the proteins and activates enzymes that begin to hydrolyze peptide bonds The amino acids are absorbed through the intestinal walls into the bloodstream for transport to the cells  COENZYMES IN METABOLIC PATHWAYS An oxidation reaction involves the loss of hydrogen, the loss of electrons, or the gain of oxygen by a substance. In a reduction reaction, there is a gain of hydrogen, a gain of electrons, or a loss of oxygen. 𝑵𝑨𝑫+ 𝑵𝑨𝑫+ (nicotinamide adenine dinucleotide) is an important coenzyme in which the B3 vitamin niacin provides the nicotinamide group, which is bonded to adenosine diphosphate (ADP). It is reduced to NADH + 𝑯+  𝑵𝑨𝑫+ The 𝑁𝐴𝐷 + coenzyme is required for metabolic reactions that produce carbon–oxygen (C=O) double bonds, such as in the oxidation of alcohols to aldehydes and ketones. An example of an oxidation–reduction reaction that utilizes 𝑁𝐴𝐷 + is the oxidation of ethanol in the liver to ethanal and NADH. FAD FAD (flavin adenine dinucleotide) is a coenzyme that contains adenosine diphosphate (ADP) and riboflavin. Riboflavin, also known as vitamin B2 consists of ribitol (a sugar alcohol) and flavin. Reduced form is FADH2  FAD FAD is used as a coenzyme when a dehydrogenation reaction converts a carbon–carbon single bond to a carbon–carbon double bond (C=C). An example of a reaction in the citric acid cycle that utilizes FAD is the conversion of the carbon–carbon single bond in succinate to a double bond in fumarate and FADH2.  Coenzyme A (CoA) Coenzyme A (CoA), which is not involved in oxidation– reduction reactions, is made up of several components: pantothenic acid (vitamin B5), adenosine diphosphate (ADP), and aminoethanethiol.  Coenzyme A (CoA) The important feature of coenzyme A (abbreviated HS–CoA) is the thiol group, which bonds to two-carbon acetyl groups to give the energy-rich thioester acetyl CoA TYPES OF METABOLIC REACTIONS TYPES OF METABOLIC REACTIONS GLYCOLYSIS: OXIDATION OF GLUCOSE GLYCOLYSIS: OXIDATION OF GLUCOSE Glycolysis is an anaerobic process; no oxygen is required. In glycolysis, a six-carbon glucose molecule is broken down to two molecules of three-carbon pyruvate. All the reactions in glycolysis take place in the cytoplasm of the cell. In the first five reactions (1–5), the energy of two ATPs is required to form sugar phosphates. GLYCOLYSIS: OXIDATION OF GLUCOSE In reactions 4 and 5, the six-carbon sugar phosphate is split to yield two molecules of three-carbon sugar phosphate. In the last five reactions (6–10), energy is obtained from the hydrolysis of the energy-rich phosphate compounds to form four ATPs. Energy Investing Reactions 1-5 Reaction 1: Phosphorylation In the initial reaction, a phosphate from ATP is added to glucose to form glucose-6-phosphate and ADP. Energy Investing Reactions 1-5 Reaction 2: Isomerization The glucose-6-phosphate, the aldose from reaction 1, undergoes isomerization to fructose-6-phosphate, which is a ketose. Energy Investing Reactions 1-5 Reaction 3: Phosphorylation The hydrolysis (energy-requiring) of another ATP provides a second phosphate group, which converts fructose-6-phosphate to fructose-1,6- bisphosphate. The word bisphosphate is used to show that the phosphates are on different carbons in fructose and not connected to each other Energy Investing Reactions 1-5 Reaction 4: Cleavage Fructose-1,6-bisphosphate is split into two three-carbon phosphate isomers: dihydroxyacetone phosphate and glyceraldehyde-3- phosphate. Energy Investing Reactions 1-5 Reaction 5: Isomerization Because dihydroxyacetone phosphate is a ketone, it cannot react further. However, it undergoes isomerization to provide a second molecule of glyceraldehyde-3- phosphate, which can be oxidized. Now all six carbon atoms from glucose are contained in two identical triose phosphates. Energy Generating Reactions 6-10 Reaction 6: Oxidation and Phosphorylation The aldehyde group of each glyceraldehyde-3-phosphate is oxidized to a carboxyl group by the coenzyme 𝑁𝐴𝐷 + which is reduced to NADH and 𝐻 +. A phosphate adds to the new carboxyl groups to form two molecules of the high-energy compound, 1,3-bisphosphoglycerate Energy Generating Reactions 6-10 Reaction 7: Phosphate Transfer A phosphorylation transfers a phosphate group from each 1,3-bisphosphoglycerate to ADP to produce two molecules of ATP. At this point in glycolysis, two ATPs are produced, which balance the two ATPs consumed in reactions 1 and 3 Energy Generating Reactions 6-10 Reaction 8: Isomerization Two 3-phosphoglycerate molecules undergo isomerization, which moves the phosphate group from carbon 3 to carbon 2 yielding two molecules of 2 phosphoglycerates Energy Generating Reactions 6-10 Reaction 9: Dehydration Each of the phosphoglycerate molecules undergoes dehydration (loss of water) to give two high-energy molecules of phosphoenolpyruvate. Energy Generating Reactions 6-10 Reaction 10: Phosphate Transfer In a second direct phosphate transfer, phosphate groups from two phosphoenolpyruvate are transferred to two ADPs to form two pyruvates and two ATPs.  Summary of Glycolysis In the glycolysis pathway, a six-carbon glucose molecule is converted to two three-carbon pyruvates. Initially, two ATPs are required to form fructose-1,6 bisphosphate. In later reactions, phosphate transfers produce a total of four ATPs. Overall, glycolysis yields two ATPs and two NADHs when a glucose molecule is converted to two pyruvates. Summary of Glycolysis  Importance of Glycolysis Glycolysis is especially relevant for tissues with high energy demands, like muscle and brain tissue, and is the primary energy pathway when oxygen is limited. Glycolysis provides a rapid source of energy, especially in cells that lack mitochondria. The pyruvate produced can enter the mitochondria to fuel the citric acid cycle (Krebs cycle) under aerobic conditions or be converted to lactate during anaerobic respiration.  Regulation of Glycolysis Below are the three control points in the glycolysis pathway Hexokinase Glucose Glucose-6-phosphate Phosphofructo Fructose-1,6- Fructose-6-phosphate kinase biphosphate Pyruvate Phosphoenolpyruvate Pyruvate kinase  Let Us Check Your Understanding Identify each of the statements as one of the following reactions: (1) isomerization, (2) phosphorylation, (3) dehydration, (4) cleavage 1) a phosphate is transferred to ADP to form ATP 2) 3-phosphoglycerate is converted to 2-phosphoglycerate 3) water is lost from 2-phosphoglycerate 4) fructose-1,6-bisphosphate splits to form two three-carbon compounds  ATP Yield from the Complete Oxidation of 1 mol of Glucose Yield of ATP Reaction Process (moles) Glycolysis (Cytoplasmic Reaction) glucose → glucose-6-phosphate 1mol consumes 1ATP -1 glucose-6-phosphate → fructose-1,6-biphosphate 1mol consumes 1ATP -1 2mol produces 2 mol glyceraldegyde-3-phosphate → 1,3-biphosphoglycerate of cytoplasmic NADH 1,3-biphosphoglycerate → 3-phosphoglycerate 2mol produces 2ATP +2 phosphoenolpyruvate → pyruvate 2mol produces 2ATP +2 PATHWAYS FOR PYRUVATE During aerobic conditions, oxygen is available to convert pyruvate to acetyl coenzyme A (CoA). When oxygen levels are low (anerobic), pyruvate is reduced to lactate. Anaerobic Pathway For Pyruvate The accumulation of lactate causes the muscles to tire and become sore. After exercise, a person continues to breathe rapidly to repay the oxygen debt incurred during exercise. Anaerobic Pathway For Pyruvate Bacteria also convert pyruvate to lactate under anaerobic conditions. In the preparation of kimchee and sauerkraut, cabbage is covered with salt brine. The glucose from the starches in the cabbage is converted to lactate. This acid environment acts as a preservative that prevents the growth of other bacteria. THE CITRIC ACID CYCLE THE CITRIC ACID CYCLE In the mitochondria, acetyl-CoA combines with oxaloacetate to form citrate. Citrate undergoes a series of transformations, releasing two molecules of CO₂ and regenerating oxaloacetate, which allows the cycle to continue. THE CITRIC ACID CYCLE Throughout the cycle, electrons are transferred to electron carriers, NAD⁺ and FAD, forming NADH and FADH₂. These molecules store energy that will be used in the next stage, the electron transport chain.  SUMMARY OF CITRIC ACID CYCLE Citric acid cycle begins when a two-carbon acetyl group from acetyl CoA combines with oxaloacetate to form citrate. In part 1 of the cycle, two carbon atoms are removed from citrate to yield two CO2 and a four-carbon compound. In part 2, the four-carbon compounds eventually regenerate oxaloacetate.  SUMMARY OF CITRIC ACID CYCLE In the four oxidation reactions of one turn of the citric acid cycle, three 𝑁𝐴𝐷+ 𝑠 and one FAD are reduced to three NADHs and one FADH2. One GDP is converted to GTP, which is used to convert one ADP to ATP.  IMPORTANCE OF CITRIC ACID CYCLE The NADH and FADH₂ molecules generated carry electrons to the electron transport chain, where they play a crucial role in the production of a large amount of ATP. The cycle is central to metabolizing carbohydrates, fats, and proteins since intermediates from the cycle are used in various biosynthetic pathways. This cycle is particularly important in tissues with high energy requirements, such as the heart, brain, and muscles.  ATP Yield from the Complete Oxidation of 1 mol of Glucose Yield of ATP Reaction Process (moles) Oxidation of Pyruvate (Mitochondrial Reaction) pyruvate → acetyl CoA + 𝐶𝑂2 2mol produces 2NADH Citric Acid Cycle (Mitochondrial Reaction) isocitrate → α-ketoglutarate + 𝐶𝑂2 2mol produces 2NADH α-ketoglutarate → succinyl CoA + 𝐶𝑂2 2mol produces 2NADH succinyl CoA → succinate 2mol produces 2GTP +2 succinate → fumarate 2mol produces 2FADH2 malate → oxaloacetate 2mol produces 2NADH ELECTRON TRANSPORT CHAIN  ELECTRON TRANSPORT CHAIN The Electron Transport Chain (ETC) is the final and most ATP- rich phase of cellular respiration, occurring in the inner mitochondrial membrane. It uses high-energy electrons from molecules like NADH and FADH₂ (generated in glycolysis and the citric acid cycle) to produce ATP.  ELECTRON TRANSPORT CHAIN Electrons from NADH and FADH₂ enter the ETC, moving through a series of protein complexes (Complexes I-IV) embedded in the inner mitochondrial membrane.  OXIDATIVE PHOSPHORYLATION As electrons pass through the complexes, they release energy, which is used to pump protons (H⁺ ions) from the mitochondrial matrix into the intermembrane space. This creates a proton gradient, or “proton motive force.”  OXIDATIVE PHOSPHORYLATION Protons flow back into the matrix through ATP synthase, a protein complex that acts as a turbine. This flow powers the synthesis of ATP from ADP and inorganic phosphate (Pi). At the end of the chain, electrons combine with oxygen and protons to form water (H₂O), completing the process.  IMPORTANCE OF ELECTRON TRANSPORT CHAIN The ETC is the major ATP producer, providing most of the energy needed for cellular processes, including muscle contraction, nerve impulses, and biosynthetic pathways. The ETC requires oxygen; without it, the chain halts, stopping ATP production and forcing cells to rely on less efficient anaerobic pathways (like glycolysis). Organs with high energy demands, such as the heart, brain, and muscles, rely heavily on the ETC for sustained energy production.  ATP Yield from the Complete Oxidation of 1 mol of Glucose Yield of ATP Reaction Process (moles) Electron Transport Chain and Oxidative Phosphorylation 2 cytoplasmic NADH formed in glycolysis each yields 2.5 ATP +5𝑎 2NADH formed in the oxidation of pyruvate each yields 2.5 ATP +5 2FADH2 formed in the citric acid cycle each yields 1.5 ATP +3 6NADH formed in the citric acid cycle each yields 2.5 ATP +15 a. In muscle and brain cells, 3ATP are produced in this step.  ATP Yield from the Complete Oxidation of 1 mol of Glucose Yield of ATP Reaction Process (moles) Glycolysis (Cytoplasmic Reaction) glucose → glucose-6-phosphate 1mol consumes 1ATP -1 glucose-6-phosphate → fructose-1,6-biphosphate 1mol consumes 1ATP -1 2mol produces 2 mol glyceraldegyde-3-phosphate → 1,3-biphosphoglycerate of cytoplasmic NADH 1,3-biphosphoglycerate → 3-phosphoglycerate 2mol produces 2ATP +2 phosphoenolpyruvate → pyruvate 2mol produces 2ATP +2  ATP Yield from the Complete Oxidation of 1 mol of Glucose Yield of ATP Reaction Process (moles) Oxidation of Pyruvate (Mitochondrial Reaction) pyruvate → acetyl CoA + 𝐶𝑂2 2mol produces 2NADH Citric Acid Cycle (Mitochondrial Reaction) isocitrate → α-ketoglutarate + 𝐶𝑂2 2mol produces 2NADH α-ketoglutarate → succinyl CoA + 𝐶𝑂2 2mol produces 2NADH succinyl CoA → succinate 2mol produces 2GTP +2 succinate → fumarate 2mol produces 2FADH2 malate → oxaloacetate 2mol produces 2NADH  ATP Yield from the Complete Oxidation of 1 mol of Glucose Yield of ATP Reaction Process (moles) Electron Transport Chain and Oxidative Phosphorylation 2 cytoplasmic NADH formed in glycolysis each yields 2.5 ATP +5𝑎 2NADH formed in the oxidation of pyruvate each yields 2.5 ATP +5 2FADH2 formed in the citric acid cycle each yields 1.5 ATP +3 6NADH formed in the citric acid cycle each yields 2.5 ATP +15 NET YIELD of ATP +32 a. In muscle and brain cells, 3ATP are produced in this step and only 30ATP overall. Glucose gives us energy Glucose goes to glycolysis to produce pyruvates