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Lecture 14 Chapter 15 Metabolism 1 Outline Metabolism ATP as the universal currency of free energy Coupled Reactions Activated carriers Regulation of metabolic processes 2 What is Metabolism The complex of physical and chemical processes occurring within a living cell or organism that are necessary for the maintenance of life Motion Active transport Biosynthesis anabolism Signal amplification ATP ADP Photosynthesis autotrophs Oxidation of fuel molecules catabolism chemoheterotroph Hydrocarbon Fuels fossil fuel biofuel glucose Contain potential energy that can be released by oxidation C6H12O6 6 O2 6 CO2 2880 kJ mol 6 H2O 6 CO2 30 ATPs 6 4H2O Energy is released from glucose in a stepwise fashion forming ATP 30 32 ATP 5 Free Energy Released by Oxidation of single carbon compounds 6 Two main types of Cellular Fuel 7 Oxidation Reduction reactions Overview Reduction Gain of e loss of oxygen gain of hydrogen Aox Bred Ared Box Oxidation Loss of e gain of oxygen loss of hydrogen 8 Metabolism Catabolism Anabolism High Enthalpy Low Entropy Higher free energy Oxidation of carbon fuel e FADH2 NADH e e e e ee e NADH Low Enthalpy High Entropy Lower free energy 9 10 The stages of catabolism 11 Adenosine 5 Triphosphate ATP Adenine base 2 Phosphoester bond Ribose sugar Phosphate tail Phosphoric Anhydride Linkages Phosphoryl Groups with High Transfer Potential in Adenosine Nucleotides Hydrolysis of Phosphoric Acid Anhydrides is Highly Favorable ATP G 30 5 kJ mol 1 Orthophosphate Pi ADP 14 J G 45 6 kJ mol 1 pyrophosphate PPi 15 Hydrolysis of Pyrophosphate Is Also Thermodynamically Favorable pyrophosphate PPi J G 33 6 kJ mol 1 Pi H H Pi Three ways to make ATP in Eukaryotes 1 Substrate level phosphorylation Phosphate is transferred to ADP in a coupled reaction involving from a molecule with an high phosphoryl group transfer potential 2 Oxidative phosphorylation during Cellular respiration by ATP phosphatase 3 Creatine kinase 17 Molecules with High Phosphoryl Group Transfer Potential 18 Coupled Reaction For Production of ATP Substrate level Phosphorylation Reactions 1 and 2 are coupled 1 PEP H2O 2 ATP H2O ADP Pi 3 PEP ADP pyruvate Pi pyruvate ATP G 62 2 kJ mol G 30 5 kJ mol Overall G 31 5 kJ mol G overall G reaction 1 G reaction 2 If the net G value G overall is sufficiently negative forming the products eg pyruvate and ATP is an exergonic process Molecules with High Phosphoryl Group Transfer Potential 20 The Large Negative Free Energy Change of ATP Hydrolysis Drives many Unfavorable Reactions in the Cell Example Phosphorylation of glucose is driven by hydrolysis of ATP ATP H2O ADP Pi glucose Pi G 6 P H2O glucose ATP G 6 P ADP G reaction 1 30 5 kJ mol G reaction 2 14 kJ mol G overall 16 5 kJ mol Coupled reactions Molecules with High Phosphoryl Group Transfer Potential 22 Three ways to make ATP in Eukaryotes 1 Substrate level phosphorylation Phosphate is transferred to ADP in a coupled reaction involving from a molecule with an high phosphoryl group transfer potential 2 Oxidative phosphorylation ATP phosphatase 3 Creatine kinase 23 Sources of ATP during Excercise Initial pool Anaerobic 24 Two important properties of high energy compounds 1 Transient forms of stored energy 2 Thermodynamically unstable Favorable spontaneous 1 Kinetically stable Does not hydrolyze unpredictably 25 The High Phosphoryl transfer Potential of ATP results from structural differences between ATP and its hydrolysis Products 1 Electrostatic Repulsion 2 Resonance Stability 3 Stabilization due to hydration 4 Increased entropy 26 Hydrolysis of ATP Causes the Relief of Charge Repulsion 27 Resonance Structures of Orthophosphate Pi 28 There are fewer resonance structures available to the phosphate of ATP than to free orthophosphate 29 Hydrolysis of ATP Increases Entropy ATP H2 O Pi P OH H O O O O P O P O O O ADP OR O 30 What is the Daily Human Requirement for ATP Resting human consume about 40 kg of ATP in 24 hours and up to 0 5 kg per minute of strenuous exercise This is equivalent to 60 kg for a 2 hr run The typical adult human body contains 50 100 g of ATP ADP Thus each ATP molecule must be recycled nearly 1300 times per day The typical ATP molecule is consumed within 1 min of its production 31 Activated Carriers during Catabolism ADP ATP NAD NADH FAD FADH2 FMN FMNH2 Reduction of NAD http classes midlandstech edu carterp courses bio225 chap05 lecture3 htm 33 Dehydrogenation Reaction reduced oxidized oxidized reduced 1 H 1 e 1 H 1 e H hydride 2 e 1 H or H 1 e Error on p 257 of text says hydrite H 2 e 34 Nicotinamide Adenine Dinucleotide NAD NAD Collects Electrons Released in Catabolism H oxidized reduced 35 Reduction of FAD FMN or FMN or FMNH2 36 FAD Flavine Adenine Dinucleotide Riboflavin a watersoluble vitamin Isoalloxazine ring D ribitol Vit B2 37 FMN an electron carrier component of the ETC Isoalloxazine ring D ribitol 38 Activated Carriers during Anabolism ADP ATP NADP NADPH 39 Reductive Biosynthesis 2 NADPH H 2 NADP 40 The structure of nicotinamide adenine dinucleotide phosphate NADP 41 Activated Carrier of Acyl Group Coenzyme A CoA or CoASH Vit B5 ADP 42 43 Two characteristics are common to activated carriers 1 The carriers are kinetically stable in the absence of specific catalysts 2 The metabolism of activated groups is accomplished with a small number of carriers 44 B3 B5 B7 B9 45 Regulation of Glucose Metabolism Normal blood levels 80 to 110 mg dL 46 Diabetes Type 1 Insulin Dependent Blood sugar remains high X 47 Diabetes Type 2 1 Type Insulin Dependent Insulin Independent Blood sugar remains high X X 48 Regulation of Metabolic Pathways 1 Amounts of enzyme are controlled 2 Accessibility to substrates is regulated 3 Catalytic activity is regulated Posttranscriptional modification of enzymes Allosteric regulation 4 Organized into pathways 49 Metabolic Pathways carbohydrates nucleotides Lipids Amino acids 50 Steady StateFlow Flowofofmetabolic Metabolicpathway flux Pathways flux 51 Reversible Pathway A B Not at equilibrium C D E equilibrium 52 Reversible Pathways Cannot be Independently Regulated A B equilibrium C D Not at equilibrium E 53 Reciprocal Pathways Glycolysis C Glucose A Pyruvate E B D F Gluconeogenesis 54 The energy status of the cell is often an important regulator of enzyme activity 55 Energy charge regulates metabolism 56 Learning Goals Be able to define metabolism Identify the factors that make ATP an energy rich molecule Explain how ATP can power reactions that would otherwise not take place Describe the


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UIUC MCB 450 - MCB450-14_SPring2015

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