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Transcript
Intermediary Metabolism How your body uses that Big Mac The Laws of Thermodynamics In every physical or chemical change, the total amount of energy in the universe remains constant, although the form of the energy may change. That is, energy can be changed from one form to another, but can never be destroyed. Intermediary metabolism is the process by which chemical energy is captured and transformed for later use in a variety of energy-utilizing processes (“work”). Energy flows through the Biosphere Thermodynamics and reactions • Energy out = Energy In – Energy Stored • ∆E=Eproducts-Ereactants • C6H12O6+6O2↔6CO2+6H2O ∆H=-673kcal/mole (here “H” is “enthalpy”, or heat content: H=E+PV) GibbsFree Energy: ∆G=∆H-T∆S. (here “S” is entropy, or disorganization, and T is the temperature) Reactions involving a decrease in free energy (ΔG<0) are spontaneous. Otherwise the reaction will not go (as written). A mole is the gram molecular weight of a compound. For glucose it is C 6*12=72 H 12*1=12 O 6*16=72 TOTAL 156 gm (5.5 oz) A calorie is the amount of heat that will raise one gram of water 1 degree centigrade. A dietary calorie is 1000 calories, or one kcal. Equilibrium and ∆G The equilibrium constant is the ratio of product concentration to reactant concentration at equilibrium: product eq K eq reactant eq ΔG0 is the “Standard Free Energy” of a reaction ( at equilibrium): ∆𝐺 𝑜 = −𝑅𝑇𝑙𝑛𝐾𝑒𝑞 The actual ΔG of a reaction is the difference between equilibrium and the actual concentration of the reactants: [𝑝𝑟𝑜𝑑𝑢𝑐𝑡] ∆𝐺 = ∆𝐺 + 𝑅𝑇𝑙𝑛 [𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡] 𝑜 Summary: Thermodynamics of Reactions 1. The direction (A→B or B→A) and energy (yield or need thereof) of a reaction is: 1. Independent of the path (mechanism) of the reaction 2. Completely dependent on the concentration of the products and reactants 2. The rate of a reaction is: 1. Independent of the energy lost or gained in the reaction 2. Completely dependent on the path (mechanism) of the reaction. A biological example: • Consider the conversion of glucose-6-phosphate to fructose-6-phosphate (Keq=0.5). • If you start with equimolar concentrations of G-6-P and F-6-P and allow the reaction to go, you will wind up at equilibrium with twice as much G6P as F6P (i.e., 1/3 is converted). Thus, F6P G6P 𝑒𝑞 𝑒𝑞 1 = = 0.5 = Keq 2 A biological example (cont’d) • The standard free energy thus is: ∆𝐺 𝑜 = −𝑅𝑇𝑙𝑛𝐾𝑒𝑞 =−(1.487cal•˚K-1mol-1)(298˚K) ln 0.5 =−(592cal•mol-1)(−0.693) =+410cal•mol-1 Here, ΔG is positive and thus the reaction will not go as written, i.e., G6P will not form F6P. BUT: this is a vital reaction and goes on all the time in your body!! How can this be?? A biological example (cont’d) • The solution: remember that the ΔG of a reaction depends on how far the concentrations of the reactants are from their equilibrium concentrations. • So to beat the game, your body utilizes a subsequent reaction that rapidly consumes the F6P as it is produced, keeping its concentration extremely low. • Here’s how it works: A biological example (cont’d) • In human red blood cells, the concentrations are: • [glucose-6-phosphate]=83mM • [fructose-6-phosphate]=14mM [𝑝𝑟𝑜𝑑𝑢𝑐𝑡] ∆𝐺 = + 𝑅𝑇𝑙𝑛 [𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡] 14 −1 = 410𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 + 𝑅𝑇𝑙𝑛 𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 −1 83 ∆𝐺 𝑜 = 410𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 −1 − 1053𝑐𝑎𝑙𝑚𝑜𝑙 −1 = −643𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 −1 Which is a rather large negative ΔG, ,meaning the reaction goes spontaneously and nearly to completion, and you live to come to CLS another day!! Energy of Activation Spontaneity (ΔG) tells us that a reaction can go, but not whether or not it will go. Heat and Catalysts Speed Up Reactions by helping the reactants overcome the energy of activation barrier. Heat gives the reactants more energy, while catalysts lower the barrier. Redox Reactions • In a redox reaction one compound is reduced (gains electrons) while its partner is oxidized (loses electrons) Redox reactions can be chained • A substance such as NAD can act as an electron carrier, carrying electrons from one reaction to another. • The NAD can be a mobile or a membrane-bound carrier. Conclusions* •By altering the concentrations of reactants and products, living cells can make unfavorable reactions go. •Catalysts speed up reactions by lowering the energy of activation. •Note that catalysts DO NOT change ∆G: they cannot make an unfavorable reaction favorable! •Energy produced by one reaction can be used by another reaction (as in redox reactions) *(take a breath; we’re done with p-chem for a while) ATP: currency of the cell ADP Pi ATP H2O enz G 7.3kcal Gcell 12.5kcal o' Intermediary Metabolism: An overview Glycolysis: details Budget: 1 glucose→2 pyruvate; 4 ATP produced, two used (net +2); 2 NADH+ produced. Some energetics of glycolysis • Glucose: C6H12O6+6O2→6CO2+6H2O ΔG0’ =-686kcal/mole • Pyruvate: C3H6O2+3O2→3CO2+3H2O ΔG0’ =-319.5kcal/mole • -686-(2x(-319.5)) = 47kcal yield for glycolysis • 2 ATP @ 12.5 kcal/mole = 25 kcal out of 47 kcal = 50% efficiency • Overall efficiency of glucose to ATP: 25/686= 3% Regulation of Glycolysis/Gluconeogenesis •Feedback Regulation •ATP and other products (NADH) •Hormonal Regulation •Insulin •Glucagon Anaerobic vs. aerobic metabolism So far we’ve used no oxygen. This is like muscles under stress. But what if there is oxygen? Then we can burn the pyruvate for energy in the Kreb’s (citric acid, TCA) cycle. After Glycolysis, the TCA cycle in the matrix of the mitochondria takes over It’s called a “cycle” for a good reason Budget: One glucose produces: 2 ATP (from glycolysis) 8 NADH+H+ (2 from glycolysis) 2 FADH2 2 GTP (=2 ATP) 6 CO2 But we still haven’t used any oxygen! Glycolysis and the TCA are versatile What happens next?? Energy from “oxidative phosphorylation” • A process to make ATP (“phosphorylation”) using oxygen. • It uses the Electron Transport Chain (ETC) in the mitochondria • The ETC is a series of redox reactions whose function it is to accept electrons from the NADH and FADH from glycolysis and the TCA (thus oxidizing and restoring them) and transfer those electrons to an acceptor (reducing it) • The ultimate acceptor is oxygen, which becomes reduced to water (H2O). The electron transport chain, like the TCA, takes place in the mitochondria But now the scene of action shifts to the inner membrane rather than the matrix. Let’s take a first look: The Electron Transport System Formation ATP: Transfer ofof electrons: Transfer of Hydrogens: The pump uses the proton gradient we just made. In most places in the body the pump uses ATP to form proton gradients Summation Substance Source # produced ATP value ATP Glycolysis 2 2 TCA 2 (from GTP) 2 Glycolysis 2 6 TCA 6 18 TCA 2 4 NADH+H+ FADH2 TOTAL 32 32 ATP x 7.3kcal/ATP= 233.6 kcal out of 673 available= 35% efficiency A gasoline engine is only about 25% efficient! What do you do when there’s no oxygen? Recycling the lactate Glycolysis Gluconeogenisis Nonshivering thermogenesis Comparison of sugar and fat: • A. Net products from oxidation of one mole of glucose (180 grams) • 34 moles ATP • 0.17 moles/gram • B. Net products from oxidation of one mole of palmitate, a fatty acid (256 grams) • 93 ATP • 0.36 moles/gram The bottom line is that fat is a much better storage form for energy than is glucose. Organ Specialization: The Absorptive Phase The Postabsorptive Phase Protein pools Carbohydrate and Fat pools Production and utilization of glucose