Energy Metabolism Handout PDF

Energy metabolism  2 Cellular respiration oxidizes biological fuels with an inorganic electron acceptor, like oxygen, to produce ATP, the cell's energy currency. 3 stages of cellular respiration: Metabolic fuel oxidation (acetyl-CoA production) which is derived GTP, from o...

Energy metabolism  2 Cellular respiration oxidizes biological fuels with an inorganic electron acceptor, like oxygen, to produce ATP, the cell's energy currency. 3 stages of cellular respiration: Metabolic fuel oxidation (acetyl-CoA production) which is derived GTP, from oxidation of glucose, fatty acids, ketone bodies, and some CO2 amino acids. The citric acid cycle (also called the Krebs cycle or the tricarboxylic acid cycle) converts pyruvate into CO2 and reduced electron carriers in the mitochondrial matrix. Oxidative phosphorylation generates ATP and water by transferring electrons to oxygen on the inner mitochondrial membrane. 3  Double membrane: outer and inner membrane consisting of proteins and phospholipid molecules Intermembrane space: space between the two membranes. Cristae: formed by inward folding of the inner membrane. Matrix: space enclosed by the inner membrane containing enzymes, proteins, ribosomes, DNA, etc. DNA: genetic material of mitochondria Functions: Generating ATP via oxidative phosphorylation (“the powerhouse of cells”), regulating cellular metabolic activity, and promoting cell growth. 4 Energy investment stage ATP accounting so ₂ far: Glycolysis – 2 ATP Kerbs – 2 ATP We need a lot more ATP! Energy harvesting stage https://en.wikipedia.org/wiki/Cellular_respiration#mediaviewer/File:CellRespiration.svg 5 Reducing equivalents/electron carriers: FADH 2 and NADH NADH Nicotinamide adenine dinucleotide The oxidized (NAD+) and reduced (NADH) forms of nicotinamide adenine dinucleotide are essential molecules in cellular energy metabolism due to their ability to transfer electrons. 6 Reducing equivalents/electron carriers: FADH 2 and NADH FADH2 Flavin adenine dinucleotide in its oxidized state is called FAD. The vitamin, riboflavin (or B2) is used to derive this compound. After being reduced, it is called FADH2. an electron carrier used to transport electrons generated in glycolysis and Krebs cycle to the electron transport chain. Flavin Riboflavin Ribitol Flavin adenine dinucleotide in the oxidized form (FAD) accepts two hydrogen atoms (each with one electron) and Adenosine becomes FADH2. 7  Oxidation of pyruvate to Acetyl-CoA Thiamine pyrophosphate (TPP), B1 This reaction involves both oxidation and decarboxylation. Pyruvate dehydrogenase complex contains 3 different enzymes each with numerous subunits. The overall reaction requires CoA-SH, NAD+, FAD and two other co-enzymes (lipoic acid and TPP). Most Acetyl-CoA enters TCA cycle, which is the final common pathway for the oxidation of carbohydrates, lipids and proteins. 8  Citric acid cycle/Krebs cycle/Tricarboxylic acid cycle (TCA) The mnemonic for The intermediates in the Krebs cycle are used memorizing the from glycolysis for the synthesis of: Fatty names of the Krebs cycle intermediates is: or the -oxidation acids, citrate is krebs special sterols substrate for making of fatty acids oxaloacetate. Reducing equivalents/electron carriers Amino for electron transport acids system (ETS) In biochemistry, the term reducing equivalent refers to any of a Heme number of chemical species which transfer the equivalent of one electron in redox reactions. 2 CO2 + 3 NADH + 1 GTP + 1 FADH2 9  Series of protons built into inner mitochondrial membrane Sequence of ETC complex NADH → Complex I → CoQ → Complex III → Complex IV → ATP synthetase  Production of 3 or 2.5 ATP/NADH FADH2 → Complex II → CoQ → Complex III → Complex IV → ATP synthetase  Production of 2 or 1.5 ATP/ FADH2 Oxidative phosphorylation: concentration gradient of H+ Only in the presence of O2 The last electron receiver in the chain is oxygen 10 Oxidative phosphorylation (OXPHOS) http://www.youtube.com/watch?v=vZz-KLK-X40 11 http://www.youtube.com/watch?v=vZz-KLK-X40  Oxidative phosphorylation the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH 2 to O 2 by a series of electron carriers. ATP is generated because the protons (H+) move through a transmembrane protein called ATP synthase (complex V). This enzyme makes ATP from ADP and Pi. 12  How does NADH cross the mitochondrial inner membrane? - NADH generated from the NAD+ glycolysis in the cytosol. regeneration - The inner membrane of mitochondria is impermeable to NADH - Electrons from NADH but not NADH itself are carried across the mitochondrial membrane using:  Glycerol 3-phosphate shuttle  Malate-aspartate shuttle 13  Malate-aspartate shuttle Glycerol 3-phosphate shuttle In heart and liver In skeletal muscles and brain From glycolysis NAD+ regeneration From glycolysis NAD+ regeneration In cytosol In matrix 2.5 molecules of ATP are produced in ETC. 2 molecules of ATP are produced in ETC. 14  ATP yield from complete oxidization of glucose 32 in heart, liver, and kidney and 30 in brain and skeletal muscle. 2  2.5 = 5 ATP 2  1.5 = 3 ATP NADH → Cpx I → CoQ → Cpx III → Cpx IV  3 or 2.5 ATP FADH2 → Cpx II → CoQ → Cpx III → Cpx IV  2 or 1.5 ATP 15  Inhibitors of OXPHOS Rotenone is produced by Oligomycin, is extraction the roots and isolated stems of several plants. from Streptomyce It is a pesticide and s, is an inhibitor mitochondrial complex I Cyanide is an of ATP inhibitor. inhibitor of synthetase. complex IV. Lonchocarpus utilis Derris elliptica 16 Summary The oxidation of fuel molecules (carbohydrates, lipids and proteins) is the source of energy used by cells: cellular respiration. Mitochondria: double membrane and “the powerhouse of cells” Krebs cycle occurs in the matrix of the mitochondria, in eukaryotes. Each turn releases 2 CO₂ molecules, 3 NADH, 1 FADH₂, and 1 ATP/GTP, serving as the final common pathway for carbohydrate, lipid, and protein oxidation. The electron transport chain, and site of oxidative phosphorylation, is found on the inner mitochondrial membrane. NADH → Cpx I → CoQ → Cpx III → Cpx IV  3 or 2.5 ATP; FADH2 → Cpx II → CoQ → Cpx III → Cpx IV  2 or 1.5 ATP. O2 is the final electron acceptor. Complex VI can be inhibited by cyanide. The glycerol-3-phosphate shuttle and malate-aspartate shuttle are for transport reducing equivalents from cytoplasm into mitochondria. The malate-aspartate shuttle produces 2.5 ATP per electron pair transferred, while the glycerol-3-phosphate shuttle produces 1.5 ATP per electron pair transferred. 17 Lehninger Principles of Biochemistry Biochemistry Ninth Edition ©2019 Eighth Edition ©2021 Lubert Stryer; Jeremy Berg David L. Nelson; Michael M. Cox ; John Tymoczko; Gregory Gatto 18  Any question?