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Energy Uses and Relationships Uses of Energy Biosynthesis Movement Active Transport Metabolism Metabolism involves • Catabolic reactions that break down large, complex molecules to provide energy and smaller molecules. • Anabolic reactions that use ATP energy to build larger molecules. Catabolism: Energy producing, oxidative, convergent Anabolism: Energy requiring, reductive, divergent Stages of Metabolism (Catabolism) Catabolic reactions are organized as Stage 1: Digestion and hydrolysis break down large molecules to smaller ones that enter the bloodstream. Stage 2: Degradation breaks down molecules to twoand three-carbon compounds. Stage 3: Oxidation of small molecules in the citric acid cycle and electron transport provide ATP energy. Stages of Metabolism (Catabolism) Stages of Metabolism (Anabolism) Anabolic reactions are organized as Stage 2: Energy (ATP) and Reduction used to convert small molecules into building blocks of larger molecules. Stage 1: Formation of macromolecules (proteins, polysaccharides, triacylglycerols, nucleic acids) from their building blocks. Summary of Metabolic Pathways Cell Structure Metabolic reactions occur in specific sites within cells. Carbohydrate breakdown and synthesis, fat synthesis DNA and RNA synthesis Recycling center Protein synthesis Fatty acid oxidation, citric acid cycle, electron transport system Mitochondrion Key Processes Occurring Inside the Mitochondrion Citric Acid (Kreb’s) Cycle Electron Transport System Fatty Acid Oxidation ATP and Energy Hydrolysis of ATP to ADP and ADP to AMP pyrophosphate bonds Other Energy-rich Phosphates phosphenolpyruvate+ H2O pyruvate + Pi + 14.8 kcal 1,3-bisphosphoglycerate + H2O phosphocreatine + H2O 3-phosphoglycerate + Pi + 11.8 kcal creatine + Pi + 10.3 kcal glucose 6-phosphate + H2O glucose + Pi + 3.3 kcal glycerol 1-phosphate + H2O glycerol + Pi + 2.2 kcal Central Energy Transfer Position of ATP Structure of Coenzyme NAD+ NAD+ • Is nicotinamide adenine dinucleotide. • Contains ADP, ribose, and nicotinamide. • Reduces to NADH when the nicotinamide group accepts H+ and 2e-. NAD+ + H+ + 2 e– NADH Structure of Coenzyme FAD FAD • Is flavin adenine dinucleotide. • Contains ADP and riboflavin (vitamin B2). Key Reaction of Coenzyme FAD FAD (flavin adenine dinucleotide) • Participates in reactions that produce a carboncarbon double bond (C=C). • Is reduced to FADH2. Oxidation —CH2—CH2— —CH=CH— + 2H+ + 2e- Reduction FAD + 2H+ + 2e- FADH2 Structure of Coenzyme A Carrier of acyl groups, for example acetyl group O || CH3—C— + HS—CoA acetyl group O || CH3—C—S—CoA acetyl CoA Digestion Overview Mouth: Starch breakdown - catalyzed by a-amylase in saliva Stomach: Hormone gastrin stimulates gastric gland secretion HCl and pepsinogen released Pepsinogen converted to pepsin (protease) Pepsin catalyzed hydrolysis of protein Small intestines: Hormone secretion stimulated Enterogastrone-feeds back to inhibit gastric juice secretion Secretin-stimulates release of pancreatic juice containing bicarbonate (neutralizes acid) Pancreozymin/cholecystokininstimulates pancreas to release digestive enzymes (proteases, pancreatic lipase, pancreatic amylase) stimulates gall bladder to release bile (contains bile salts: emulsifying agents) Intestinal juice also contains variety of digestive enzymes (maltase, sucrase, lactase, peptidases, nucleases) Summary of Carbohydrate MetabolicPathways Glycolysis: breaking down glucose Gluconeogenesis: synthesis of new glucose Glycogenesis: synthesis of glycogen Glycogenolysis: breakdown of glycogen Carbohydrate Catabolism Stage 2: Glycolysis • Is a metabolic pathway that uses glucose, a digestion product. • Degrades six-carbon glucose molecules to three-carbon. pyruvate molecules. • Also pathway for breakdown of other monosaccharides (fructose, galactose, ribose) Glycolysis:Overview Consists of two phases Energy-investing phase Reactions 1 - 5: glyceraldehyde 3-phosphate + glucose + 2 ATP dihydroxyacetone phosphate + 2 ADP Energy-generating phase: Reactions 6 - 10 2 glyceraldehyde 3 phosphate +4 ADP + 2 Pi + 2 NAD+ 2 pyruvate + 4 ATP + 2 NADH + 4 H+ + 2 H2O Glycolysis:Reactions 1-5 Energy-Investment Phase 4 1 3 2 5 Glycolysis: Reactions 6-10 Energy-producing Phase 9 6 8 7 10 Glycolysis: Overall Reaction In glycolysis, • Two ATP add phosphate to glucose and fructose-6-phosphate. • There is a net gain of 2 ATP and 2 NADH. • Four ATP are formed in energy-generation by direct transfers of phosphate groups to four ADP. C6H12O6 + 2ADP + 2Pi + 2NAD+ glucose 2C3H3O3- + 2ATP + 2NADH + 4H+ + 2 H2O pyruvate Pathways for Pyruvate Pyruvate: Aerobic Conditions Under aerobic conditions (oxygen present), • Three-carbon pyruvate is decarboxylated producing CO2 and an aldehyde group. • The aldehyde group is oxidized to an acetyl group. • The acetyl group is transferred to coenzyme A O O pyruvate dehydrogenase CH3—C—C—O- + HS—CoA + NAD+ pyruvate O CH3—C—S—CoA + CO2 + NADH + H+ acetyl CoA Glycolysis: Anaerobic Conditions Fermentation Fermentation • Occurs in anaerobic microorganisms such as yeast. • Decarboxylates pyruvate to acetaldehyde, which is then reduced to ethanol. • Regenerates NAD+ to continue glycolysis. O O CH3—C—C—O- + NADH + H+ pyruvate OH CH3—CH2 + NAD+ + CO2 ethanol Pyruvate: Anaerobic Conditions Under anaerobic conditions (without oxygen), • Pyruvate is reduced to lactate. • NADH oxidizes to NAD+ allowing glycolysis to continue. O O lactate dehydrogenase CH3—C—C—O- + NADH + H+ pyruvate OH O CH3—CH—C—O- + NAD+ lactate Lactate in Muscles During strenuous exercise, • Oxygen in the muscles is depleted. • Anaerobic conditions are produced. OH O • Lactate accumulates. C6H12O6 + 2ADP + 2Pi glucose CH3—CH—C—O- + 2ATP lactate • Muscles tire and become painful. • After exercise, a person breathes heavily to repay the oxygen debt and reform pyruvate in the liver. Cori Cycle The Cori cycle • Is the flow of lactate and glucose between the muscles and the liver. • Occurs when anaerobic conditions occur in active muscle and glycolysis produces lactate. • Operates when lactate moves through the blood stream to the liver, where it is oxidized back to pyruvate. • Converts pyruvate to glucose, which is carried back to the muscles. Cellular Regulation of Glycolysis Glycolysis is regulated by three enzymes, • Reaction 1 Hexokinase is inhibited by high levels of glucose-6-phosphate, which prevents the phosphorylation of glucose. • Reaction 3 Phosphofructokinase, an allosteric enzyme, is inhibited by high levels of ATP and activated by high levels of ADP and AMP. • Reaction 10 Pyruvate kinase, another allosteric enzyme is inhibited by high levels of ATP or acetyl CoA, activated by fructose 1,6bisphosphate. Glycolysis (Animated Version) electron transport system acetyl-CoA NADH + H+ CoA blood glucose CO2 NAD+ irreversible (control pt) aerobic cellular ATP glucose blood irreversible (control pt) phosphoenolpyruvate (2) pyruvate (2) hexokinase lactate ADP mitochondrion ATP (2) anaerobic NAD+ glucose 6-phosphate ADP (2) pyruvate kinase NADH + H+ H2O (2) 2-phosphoglycerate (2) cytoplasm 3-phosphoglycerate (2) fructose 6-phosphate ATP ADP irreversible (control pt) fructose 1,6-bisphosphate ATP (2) phosphofructokinase glyceraldehyde 3-phosphate dihydroxyacetone phosphate NAD+ Pi NADH + H+ ADP (2) 1,3-bisphosphoglycerate (2) Gluconeogenesis: Glucose Synthesis Gluconeogenesis is • The synthesis of glucose from carbon atoms of noncarbohydrate compounds. • Required when glycogen stores are depleted. Gluconeogenesis: Glucose Synthesis Glucose is synthesized from noncarbohydrates such as lactate, some amino acids, and glycerol after they are converted to pyruvate or other intermediates. Seven reactions are the reverse of glycolysis and use the same enzymes. Three reactions are not reversible. Reaction 1 Catalyzed by hexokinase glucose + ATP glucose 6-phosphate + ADP Reaction 3 Catalyzed by phosphofructokinase fructose 6-phosphate + ATP fructose 1,6-bisphosphate + ADP Reaction 10 Catalyzed by pyruvate kinase phosphoenolpyruvate + ADP pyruvate+ ATP Gluconeogenesis: Pyruvate to Phosphoenolpyruvate Conversion of pyruvate to phosphoenolpyruvate uses two reactions that replace the reverse of reaction 10 of glycolysis. Reaction 1: Pyruvate adds a carbon to form oxaloacetate. (Carboxylation: Uses 1 ATP) Reaction 2: A carbon is removed and a phosphate added to form phosphoenolpyruvate. (Uses 1 GTP) Total energy cost = 1 ATP + 1 GTP = 2 ATP Phosphoenolpyruvate to Fructose-1,6-bisphosphate • Phosphoenolpyruvate is converted to fructose-1,6bisphosphate using the same enzymes in glycolysis. • Uses 2 ATP and 2 NADH. Glucose Formation Glucose forms when • A loss of a phosphate from fructose-1,6-bisphosphate forms fructose-6-phosphate and Pi. • A reversible reaction converts fructose-6-phosphate to glucose-6-phosphate. • A phosphate is removed from glucose-6-phosphate. • No ATP is produced. Gluconeogenesis: Overall Reaction In gluconeogenesis, • 2 ATP and 2 GTP are used to convert pyruvate to phosphoenolpyruvate. • 2 ATP are used to convert 3-phosphoglycerate to 1,3bisphosphoglycerate. • 2 NADH are used to convert 1,3-bisphosphoglycerate to glyceraldehyde 3-phosphate. • There is a net use of 4 ATP, 2GTP, and 2 NADH. 2C3H3O3- + 4ATP + 2 GTP + 2Pi + 2NADH pyruvate C6H12O6 + 4ADP + 2 GDP + 2NAD+ glucose Regulation of Glycolysis and Gluconeogenesis TABLE 22.2 Glycogenesis Glycogenesis • Stores glucose by converting glucose to glycogen. • Takes place in liver and skeletal muscle. • Operates when high levels of glucose-6-phosphate are formed in the first reaction of glycolysis. • Does not operate when energy stores (glycogen) are full, which means that additional glucose is converted to body fat. Formation of Glucose-6-Phosphate In glycogenesis • Glucose is initially converted to glucose 6-phosphate using ATP. O - O P O CH2 O- O OH OH OH glucose-6-phosphate hexokinase OH Formation of Glucose-1-Phosphate Glucose-6-phosphate is converted to glucose-1-phosphate. O H O CH2 - O P O CH2 O- O O OH OH OH glucose 6-phosphate O OH OH O P O- OH OH O- glucose 1-phosphate Formation of UDP-Glucose UTP activates glucose-1phosphate to form UDPglucose and pyrophosphate (PPi). O CH2OH H O OH O OH O O O P O P O CH2 OH - O - O UDP-glucose OH N N O OH Glycogenesis: Glycogen The glucose in UDP-glucose adds to glycogen (glucose)n. UDP-glucose + (glucose)n (glucose)n+1 + UDP The UDP reacts with ATP to regenerate UTP. UDP + ATP UTP + ADP glycogen synthase Diagram of Glycogenesis glycogen synthase hexokinase Glycogenolysis In glycogenolysis • Glycogen is broken down to glucose. • Glucose molecules are removed one by one from the nonreducing end of the glycogen chain to yield glucose-1phosphate. glucose 6-phosphatase glycogen phosphorylase Glycogenolysis (First Reaction) glycogen-glucose + Pi glycogen phosphorylase glycogen + glucose-1-phosphate • Glycogen phosphorylase catalyzes removal and phosphorylation of glucose from non-reducing end, producing glucose 1-phosphate. • Glycogen phosphorylase activated by glucagon (liver) (low blood glucose) AMP (skeletal muscle)(energy need) Epinephrine (emergency energy signal) Liver: increase blood glucose Skeletal muscle: provide fuel for glycolysis Glycogen phosphorylase inhibited by insulin (liver and skeletal muscle) glycogen phosphorylase Hormonal Control Activated by glucagon (liver) and epinephrine (liver and muscle) Inhibited by insulin (liver and muscle) Glycogenolysis: Second Reaction Isomerization of Glucose-1-phosphate • The glucose-1-phosphate isomerizes to glucose-6phosphate, which enters glycolysis for energy production (primarily in skeletal muscle). Hydrolysis of Glucose 6-phosphate Glucose 6-phosphate • Is not converted by skeletal muscle to glucose because muscle lacks glucose 6-phosphatase. • Hydrolyzes to glucose in the liver and kidney, where glucose 6-phosphatase is available providing free glucose for the brain and skeletal muscle. glucose 6-phosphatase Summary of Glucose Pathways Blood glucose Cell insulin (+) insulin (+) glucagon (–) glucagon (–) glucose ATP glucagon (+) insulin (–) glycogenesis glycogenolysis ADP glucose 6-P glucagon (+) insulin (–) gluconeogenesis glycolysis glucagon (+) glycogen NAD+ insulin (+) glucagon (–) insulin (–) NAD+ NADH pyruvate lactate anaerobic