Metabolic Pathways, Cellular Energy Transfer and Oxidative Phosphorylation PDF

Metabolic pathways, cellular energy transfer and oxidative phosphorylation SI2101- Introductory Physiology Dr. Nicole Burns [email protected] Learning Outcomes Chapter 3: Metabolic Pathways Energy ◦ Production ◦ Glycolytic system ◦ Aerobic Energy Metabolism ◦ Electron...

Metabolic pathways, cellular energy transfer and oxidative phosphorylation SI2101- Introductory Physiology Dr. Nicole Burns [email protected] Learning Outcomes Chapter 3: Metabolic Pathways Energy ◦ Production ◦ Glycolytic system ◦ Aerobic Energy Metabolism ◦ Electron transport chain-oxidative phosphorylation ◦ Describe how carbohydrates, lipids and proteins contribute to ATP production PHYSIOLOGY, SCHOOL OF MEDICINE  Energy Transfer First Law of Thermodynamics—Conservation of Energy Energy can neither be created nor destroyed, but only transformed from one form to another without being depleted Chemical energy stored within a nutrient’s bonds does not immediately dissipate as heat during energy metabolism –A large portion of energy remains as chemical energy and then changes into mechanical energy and ultimately heat energy 3 Energy from Food The cell’s two major energy transforming activities 1) Extract potential energy from food and conserve it within the bonds of ATP 2) Extract and transfer the chemical energy in ATP to power biologic work. Adenosine Triphosphate (ATP) The Energy Currency Energy liberated during ATP breakdown transfers directly to other energy-requiring molecules Energy from ATP powers all forms of biologic work, making ATP the cell’s “energy currency” In degradation of 1 mole of ATP-to-ADP, the outermost phosphate bond splits and liberates 7.3 kilocalories of free energy ATP + H2O  ADP + P − 7.3 kcal·mole−1 5 ATP Synthesis Limited ATP supply= regulation of energy metabolism 80 to 100g ATP stored at any one time ATP must be continuously resynthesized at its rate of use Physiology, School of Medicine ATP Production University ofGalway.ie ATP-PCr System Phosphocreatine ◦ PCr reserve in muscle readily converted to sustain activity for 3-15s ◦ The main function of this system is to maintain ATP levels. Carbohydrate Lipid Protein Macronutrients Energy Release from Macronutrients Three stages lead to release and energy conservation by cells for biologic work: Stage 1: Digestion, absorption, and assimilation of relatively large food macromolecules into smaller subunits Stage 2: Degrades amino acids, glucose, fatty acids and glycerol units into acetyl coenzyme A Stage 3: Acetyl-coenzyme A degrades to CO2 and H2O with considerable ATP production  Carbohydrates Energy (calories) Molecular formula: (CH2O)n Classified in three groups: Monosaccharide, oligosaccharide, or polysaccharide Differ in number of simple sugars linked in each molecule Storage form of carbohydrates in the body is glycogen University ofGalway.ie  Lipids Molecular formula: made of C, H, O ↑↑ Hydrogen to oxygen ratio Molecular structure: fatty acids Three groups: Simple lipids- neutral fats, triglyceride (1 glycerol + 3 fatty acids) Compound lipids- phospholipids, glycolipids, and lipoproteins Derived lipids- cholesterol Energy Source and Reserve University ofGalway.ie  Protein Molecular structure: Contain C, H, O And ~16%Nitrogen, and sulfur, occasionally phosphorus, cobalt, iron Peptide bonds link amino acids (AA) together A combination of ~50AA = a protein Over 80,000 different proteins exist in the human body University ofGalway.ie Copyright © 2001, Lippincott, Williams & Wilkins Two forms of carbohydrate breakdown: 1. Anaerobic (rapid) glycolysis results in pyruvate- to-lactate formation with the release of about 5% of energy within the original glucose molecule 2. Aerobic (slow) glycolysis results in pyruvate-to- acetyl-CoA-to-citric acid cycle and electron transport of the remaining energy within the original glucose molecule C6H12O6 + 6O2 = 6CO2 + 6H2O – ∆G 686 kcal/mol University ofGalway.ie Anaerobic Glycolysis Breakdown of glucose via special glycolytic enzymes Occurs in the cytoplasm Begins once G-6-P is formed Generates only about 5-10% of the total ATP available from a glucose molecule Anaerobic (rapid) glycolysis regulated by Three factors regulate glycolysis: 1. Four key glycolytic enzymes: hexokinase, phosphorylase, phosphofructokinase, pyruvate kinase 2. Levels of fructose 1,6-diphosphate 3. Oxygen in abundance inhibits glycolysis University ofGalway.ie  Substrate–Level Phosphorylation in Glycolysis Energy transferred from substrate (CHO) to ADP by phosphorylation in rapid glycolysis in anaerobic reactions is called substrate– level phosphorylation During intense exercise (or when O2 is not available) when hydrogen oxidation doesn't keep pace with production, pyruvate temporarily binds hydrogen to form lactate  Figure 3.43 Anaerobic Metabolism and the Two Fates of Pyruvate: Entry into the Krebs Cycle or Conversion to Lactate The electron transport chain cannot process all of the hydrogen joined to NADH NAD+ “frees up” as pairs of “excess” nonoxidized hydrogens combine temporarily with pyruvate to form lactate © McGraw Hill, LLC 21  Figure 3.44 Formation of Acetyl Coenzyme A from Pyruvate with the Formation of a Molecule of Carbon Dioxide © McGraw Hill, LLC 22 Aerobic (slow) Glycolysis: The Citric Acid Cycle Rapid glycolysis releases only about 5-10% of the total energy within glucose; the remaining energy releases when pyruvate converts to acetyl-CoA and enters the citric acid cycle (also called the Krebs cycle) The citric acid cycle represents the second stage of carbohydrate breakdown to produce CO2 and hydrogen atoms within the mitochondria Pyruvate + NAD+ CoA → Acetyl-CoA + CO2 + NADH + + H+ University ofGalway.ie  Citric Acid Cycle (11 Steps) Copyright © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins Electron Transport and Oxidative Phosphorylation 1 2O2  NADH  H  3ADP  3Pi H2O  NAD  3ATP Figure 3.46 Electron Transport and Oxidative Phosphorylation, McGraw Hill, LLC 25  Figure 3.47 Pathways of Glycolysis and Aerobic Glucose Catabolism and Their Linkage to ATP Formation © McGraw Hill, LLC 26  Energy Release from Fat Three specific energy sources for fat catabolism: 1. Triacylglycerols stored directly in muscle 2. Circulating triacylglycerols in lipoprotein complexes 3. Circulating free fatty acids mobilized from triacylglycerols in adipose tissue University ofGalway.ie Glycerol and Fatty Acid Catabolism Copyright © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins Glycerol and Fatty Acid Catabolism, cont. For each 18-carbon fatty acid molecule, 147 molecules of ADP phosphorylate to ATP during β-oxidation and citric acid cycle metabolism Each triacylglycerol molecule contains three fatty acid molecules to form 441 ATP molecules from the fatty acid components (3 X 147 ATP) 19 ATP molecules form during glycerol breakdown to generate 460 molecules of ATP for each triacylglycerol molecule catabolized University ofGalway.ie Copyright © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins  Energy Release From Protein 1st nitrogen removal from AA molecule Some AA are glucogenic- yield intermediates for glucose synthesis via gluconeogenesis (alanine) ◦ Glucose transported to muscles cell for energy (glycolysis) Some AA are ketogenic- yield acetyl-CoA or acetoactetate ◦ Catabolized for energy during citric acid cycle Protein breakdown facilitates water loss  Figure 3.54 The Relationships Between the Pathways for the Metabolism of Protein, Carbohydrate (Glycogen), and Fat (Triglyceride) © McGraw Hill, LLC 31 Summary Transfer of energy from breakdown of food molecules to ATP (Adenosine Triphosphate) is accomplished by 3 related metabolic pathways: Glycolysis (Anaerobic Respiration): Carbohydrate breakdown only, occurs in cytoplasm. Does not require O2 and forms a small amount of ATP. Citric Acid (Krebs) Cycle: All nutrients (carbohydrates, proteins or fats) can participate, occurs in mitochondria. Requires O2 (an aerobic process) and generates a small amount of ATP. Oxidative Phosphorylation (Electron Transport Chain): All nutrients can participate, occurs in mitochondria. Requires O2 (an aerobic process) and generates a large amount of ATP. The ATP formed from food breakdown is used to perform cellular work, such as muscle contraction, nerve impulse conduction, active transport, etc. McGraw Hill, LLC