MCB 450 1st Edition Lecture 14 Outline of Last Lecture I Enzyme Regulation Allostery II Conformational Changes in Hemoglobin upon O2 binding III Ways to Regulate Enzymes Outline of Current Lecture I Metabolism II ATP as the universal currency of free energy III Coupled Reactions IV Activated carriers V Regulation of metabolic processes Current Lecture What is Metabolism Glucose most used fuel for cells in the body Also used to supply other biomolecules Collection all of the catalytic activity in the cells All of the energy comes from ATP adenotriphosphate Changes to adenosinediphosphate Two ways ADP changes to ATP photosynthesis and oxidation of fuel molecules Without this constant flow of energy the organism would be dead Hydrocarbon Fuels Hydrocarbons fatty acids glucose o O H C Basically combustion of hydrocarbons is the oxidation of carbons and heat is released in this reaction 1 molecule of glucose and generate 30 ATPs Energy is released from glucose in a stepwise fashion forming ATP Glycolysis Conversion of a 6 carbon glucose to pyruvate Then pyruvate can then be oxidized further and forms additional ATP Free Energy Released by Oxidation of single carbon compounds Left most reduced Right most oxidized These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute To go from reduced to oxidized form of a carbon you release free energy Two main types of cellular fuel Fatty acid gives more energy because it is more reduced o Burning of fatty acid is more efficient Fatty acids stored in adipose triacylglycerols Glucose stored in glycogen Oxidation Reduction reactions overview Oxidation and reduction reactions are coupled together o When one happens the other has to happen as well OIL oxidation loss of electrons RIG reduction gain of electrons Metabolism Oxidize all of these carbons to maximize the energy released Energy that is released is captured by ATP and then the electrons are captured by three different electron carriers NADH NADPH FADH2 Then the energy is used to synthesize more ATP Anabolism is opposite of catabolism Energy for anabolism comes from the intermediates in catabolism Will also need a supply of electrons which comes from the NADPH electron carrier The Stages of Catabolism 3 stages of catabolism o Digestion fats polysaccharides proteins are broken down into building blocks fatty acids and glycerol glucose and other sugars and amino acids building blocks then absorbed through intestinal wall and into blood then delivered to different cells throughout the body o Creation of Acetyl CoA from the building blocks and in this process will generate electrons that are used later in the citric acid cycle o Citric acid cycle is the 3rd step extra electrons are delivered the electron transport chain which is used oxidative phosphorylation o CO2 and O2 used in citric acid cycle is why you need to breathe and is why you need more oxygen when you exercise Adenosine 5 Triophosphate ATP ATP made of ribose sugar component adenine base and a phosphate tail Make sure to still know principles from first half of course will still need to know them Phosphoric Anhydride Linkages Bonds between alpha beta and beta gamma are phosphoanhydride bonds which are very high energy The less phosphates attached means the less energy present in the molecule due to the presence of phosphoric anhydride bonds Hydrolysis of Phosphoric Acid Anhydrides is Highly Favorable ATP ADP and ATP AMP Ppi are both thermodynamically favorable reactions delta G Three ways to make ATP in Eukaryotes Substrate level phosphorylation is the addition of a phosphate to ADP to create ATP Molecules with High Phosphoryl Group Transfer Potential Decreasing order of delta G values Blue lines PEP Red lines ATP and ADP Green lines AMP How much energy would you need to reverse the reaction of ATP ADP o 30 5 kJ mole Coupled Reaction for Production of ATP Delta G prime reaction 1 delta G prime reaction 2 2 delta G prime overall Pi phosphate The Large Free Energy Change of ATP Hydrolysis Drives Many Unfavorable Reactions in the Cell First reaction of glycolysis ATP hydrolysis drives metabolism by shifting the equilibrium Keq of coupled reactions by a factor of 10 8 in cells Molecules with High Phosphoryl Group Transfer Potential Since ATP is in the middle of the energy table you can think of ATP of being well placed in the between the molecules used for energy ROBIN HOOD of energy molecules takes from the rich and gives to the poor Sources of ATP during Exercise No way to store ATP have to continously produce it or the organism will die Aerobic metabolism o Substrate level phosphorylation and oxidative phosphorylation Two important properties of high energy compounds 2 ATP ADP Pi delta G 30 5 kJ mole Even though spontaneous it still requires energy to get over the activation energy WHY you need ENZYMES to get over activation barrier 3 high activation energy enzyme Hydrolysis of ATP Causes the Relief of Charge Repulsion ATP 4 negative charges ADP 3 negative charges AMP 2 negative charges So it is thermodynamically favorable for it to go from 4 or 3 negative charges to 2 negative charges Hydrolysis of ATP Increases Entropy Go from two molecules to 3 molecules means that entropy increases and thus more thermodynamically favorable What is Daily Human Requirement for ATP ATP will be used up within the minute of being made again why ATP has to be constantly made Activated Carriers during Catabolism Bottom 3 are coenzymes and are electron carriers Reduction of NAD NAD oxidation two hydrogen atoms will be removed along with 2 electrons and added to the NADH which creates NADH H Dehydrogenation Reaction ERROR in textbook it is a hydride NOT a hydrite Nicotinamide Adenine Dinucleotide NAD NAD contains AMP and Nicotinamide derived from niacin vit B3 Reduction of FAD FMN Can pick up two electrons and two full hydrogen ions Ex FMN FMNH2 FAD FAD Flavine Adenine Dinucleotide Reductive Biosynthesis 2 NADPHs supply 2 hydrides 2 H 4 e Left keto group Right methylene group The structure of nicotinamide dinucleotide phosphate NADP Only difference between the two is the OPO3 2Activated Carrier of Acyl Group Don t have to remember the structure of the coenzyme A but need to recognize the S group which will bind to the CoA C S thioester bond C O Oxygen ester bond Regulation of Glucose Metabolism Know these diagrams well Too high blood sugar levels and too low
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