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. Lecture 6 These are the notes from Professor Starnes’ lecture of Clinical Human Physiology. These come from the slideshows provided by the professor and include extra notes and explanations. Highlighted or bolded information are things that I believe to be information that is important to look over multiple times. The notes in red are my personal additions and quotes of Professor Starnes from the class lecture. Outline of Last Lecture I. Metabolic Reactions and Energy II. Reaction Rates Outline of Current Lecture I. 3.4 ATP: The Medium of Energy Exchange II. 3.5 Glucose Oxidation: The Central Reaction of Energy Metabolism III. 3.6 Stages of Glucose Oxidation: Glycolysis Current Lecture ATP - ATP- for biological systems is stored within the phosphate groups. Note negative charges. Your instructor will demonstrate energy conversion o Has its energy because the negative charges repel because they are the same. Enzyme cuts rope, phosphates fly apart and propel mechanical work. - ATP Synthesis- Energy from exergonic reactions is used to synthesize adenosine triphosphate (ATP) o ATP synthesis means how our body makes ATP o ADP + Pi + energy  ATP (+ H2O) Just replacing one bond to reattach Pi – don’t have to synthesize entire molecule o E = +7 kcal/mole (how much energy is in the phosphate bond). Your book. Based on conditions different from those in cells. Actual value varies depending on relative concentrations of reactants (ADP + Pi) and product (ATP) o 2 types of ATP synthesis reactions  Substrate-level phosphorylation. Does not involve O2 - X-P + ADP  X + ATP Ex. - Creatine kinase  Oxidative phosphorylation: requires electron transport chain & O2 - ADP + Pi  ATP KIN 292 1st Edition- ATP Homeostasis- Several metabolic pathways coordinate with one another to maintain ATP concentration constant at all times and under all conditions. Variation in speed, capacity, and location of ATP synthesis o Some pathways are in the cytosol, some are in the mitochondria o Most pathways in the cytosol make synthesis happen faster Creatine kinase reaction – fastest, smallest capacity. Location: Cytosol. Very important in muscle metabolism. Minor pathway in most organs Glycolysis – next fastest, limited capacity. Cytosol Aerobic glucose oxidation - pretty fast, decent capacity. Mitochondria Fatty acid oxidation – considerably slower than above, unlimited capacity. Mitochondria Protein oxidation – very, very slow; big capacity, but lethal if overused. Mitochondria (mostly) & cytosol - Changing concentration difference between reactants and products affects energy change (∆E) of a reaction. Remember mechanical box! o The greater the difference between the reactant and the product, the more energy that will be produced. ATP ← ADP + Pi (+∆E) Endergonic synthesis reaction ATP → ADP + Pi (-∆E) Exergonic hydrolysis reaction for cell work [5] - [0.02] [2.2] ~ mM at rest; +/-∆E approx 10.1 kcal [4.8] - [0.22] [2.4] ~ mM exercise +/-∆E approx 8.6 kcal - Decrease in ATP and increase in ADP & Pi results in increase in entropy (decreased order) and less energy in ATP bond - Note: If ATP decreases by 0.2 mM, then ADP will increase by the same amount. 4%↓ in ATP results in 1,100%↑ in ADP!! - ADP is an important regulator of enzyme activity in metabolic pathways. - Low initial concentration of ADP and its huge relative increase make it one of the most important stimulators of ATP production. ATP itself is much less important in regulating its own production. - [ADP] would be in the “enzyme regulating zone” of figure below (left side) and [ATP] would be too high (on right side) and not change much.- Bottom line – the breakdown products of ATP (ADP & Pi) are very strong regulators of metabolism and change dramatically in order to keep ATP constant at all times. - Creatine kinase reaction – (remember, this takes place in the cytosol)the fastest ATP producing pathway in the body. It’s reversible and it’s a near equilibrium enzyme. Obeys Law of Mass Action - Tertiary structure of Creatine kinase with Creatine phosphate (smaller molecule on left) and ADP Law of Mass Action - Increased reactant concentration (relative to product) pushes a reaction forward - Increased product concentration (relative to reactant) pushes a reaction in reverse - Equilibrium does not necessarily mean that you have equal amount on both the reactant and product sides - aA + bB - cC + dD (a-d = number of molecules) - These reactions have an Equilibrium constant, For CK: K = [ATP] [Cr] = 100 [ADP] [CrP] Creatine Kinase Reversibility ADP + Pi -ATP CrP -Cr + Pi Pi is either connected to Cr or ADP CK ADP + CrP -ATP + Cr - ATP is used to make creatine phosphate. The problem in ATP being used to create creatine is that it increases the amount of ATP in the body. It can only work if other metabolic pathways have been made to synthesis the extra ATP. - CrP and ATP have same ∆E at equilibrium - CrP is used to phosphorylate ADP (synthesize ATP) when product/reactant ratio is <100; - ATP used to phosphorylate Cr (synthesize CrP) when product/reactant ratio is >100 ATP homeostasis and CK - If ATP used to make CrP, another ATP producing pathway must replace ATP immediately because ATP cannot be allowed to drop. - Muscle contraction is slowed and other things are also adversely affected if ATP drops.- Most likely will be an aerobic pathway that replenishes ATP - Figure 3.24 Metabolic pathways involved in protein, glycogen/glucose, and fat metabolism. Our author considers glucose oxidation to be the central reaction in energy metabolism because it is used in all parts of the body and other nutrients share some of the ATP producing pathways - Figure 3.13 The coupling of reactions in energy transfer. General scheme - Glucose oxidation: The central reaction of energy metabolism many ATPs + heat –686 kcal/mole - Glucose oxidation occurs in 4 stages: o Glycolysis -- cytosol o Krebs cycle -- mitochondria o Electron transport chain -- mitochondria o Oxidative phosphorylation – mitochondria Energy Change in Glucose Oxidation o Energy released during glucose oxidation = -686 kcal o Energy in 38 ATP = (38 moles × 7 kcal/mole) =