Metabolism & Energy Relationships 1 Metabolism and Energy Relationships Signaling Molecules Regulate Fuel Uptake and Efficiency Leptin deficient mouse Metabolism and Energy • Information Metabolism (Genetic Continuity and Evolution) • Intermediary Metabolism (Interconversion of Chemical Metabolites Used to Obtain Energy) Information Metabolism Storage of Genetic Information Intermediary Metabolism Interconversions of chemical intermediates catalyzed by enzymes (proteins) Enabling Technology: Radioactive Tracers Free energy decreases spontaneously Storage and Interconversion of Energy ATP Energy ATP Is the Energy Currency of the Cell Electrochemical Potential Energy = Concentration Gradient + Charge Gradient Interconversion Between Electrochemical Gradients and Bond Energy (Ion Pump) Brownian Motions Drives Molecular Machines (Ion Pumps) Metabolic Strategies: Regulate Flux Through the System A ÅÆ B Æ C ÅÆ D ÅÆ E Æ F ÅÆ G ÅÆ H Æ I ÅÆ J Regulated Steps in Pathway Involve Energy Expenditure Steps That Are Readily Reversible Are Not Regulated Regulation of Metabolism • Post-translational Modifications (Proteolytic Activation; Phosphorylation) • Allosteric Regulation (Binding of Small Molecules) • Changes in Expression Levels (Transcriptional Activation) Phosphorylation Promotes Complex Formation Post-translational Modifications Allosteric Regulation Oligomeric Enzyme ADP F 1,6 P Allosteric binding site Substrate binding site Transcriptional Activation Substrate Channeling Amplification Involves Multiple Types of Regulation Cells Subdivide Their Tasks Into Cellular Compartments That Facilitate Coordinate Regulation of Metabolism Location, Location, Location In General • Catabolic Reactions Take Place in the Mitochondria • Anabolic Reactions Take Place in the Cytosol Compartmentalization Electrons Are Shuttled Through Mitochondria Electrochemical Gradient Is Used to Make ATP ATP Synthase Converts Electrochemical Gradient Into ATP Binding Change Mechanism Rotary Motion Was Directly Measured Respiratory Control Mechanisms Regulate Rates of ATP Synthesis cytosol OM IM Generation of Oxygen Radicals During Normal Metabolism O2 O2• Sensors of Oxidative Stress Down-regulate Energy Utilization and -Decrease Oxidative Stress Through Respiratory Control Mechanisms NO• + O2• - Decreased ATP Utilization ONOOCO2 HO NO 2
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