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ATP homeostasis Energy systems homeostasis • ATP – Common metabolic intermediate – Powers muscular contraction – Cell work – Well-maintained over wide variations in energy turnover Energy homeostasis • 3 basic energetic systems – Immediate (ATP-PCr) – Non-oxidative: anaerobic glycolysis – Oxidative: oxidative phosphorylation Immediate energy systems Ca2+ • ATP + actin + myosin →Actomyosin + Pi + ADP + energy ATPase • ATP +H2O → ADP + Pi • ATP then resynthesized by Creatine kinase and adenylate kinase reactions in immediate energy systems • Creatine kinase (CPK) is the enzyme that releases the energy stored in PCr to resynthesize ATP • The depiction at the R shows the “creatine phosphate shuttle” • Exceptionally small amounts of stored ATP and PCr (515s) • These reactions occur in cytoplasm Immediate energy systems • ATP broken down to ADP and Pi – A buildup of ADP and Pi stimulate metabolism • A buildup of ADP also inhibits the breakdown of ATP • ATP ADP + Pi – Thus, Adenylate kinase reaction: • ADP + ADP ATP + AMP – Used during very high energy turnover Non-oxidative energy sources (continued) Nonoxidative energy sources • Glycogenolysis/glycolysis – Depends on the start point – Breaks glucose (glycogen) down to pyruvate – Pyruvate then converted to lactate – Occurs in cytoplasm – Importance increases for events lasting longer than 15s and less than a couple of min. Oxidative energy sources Glycolysis→pyruvate Oxidative energy sources • Can come from three primary sources – Carbohydrate (glucose/glycogen) – Fat – Protein • Significant stores of fat • Thus, the body will use mostly fat at rest • Complete oxidation of glucose – C6H12O6 + 6O2 → 6CO2 + 6H2O + 36 ATP • Complete oxidation of palmitate (16C fatty acid) – C16H32O2 + 23O2 → 16CO2 + 16H2O + 129 ATP – And there are 3 fatty acids per molecule of fat (so, 387 ATP) • Oxidation of amino acids – Tricky and complicated – Must be deaminated or transaminated (NH2 group removed or converted to something else) Deamination glutamate ketoglutarate Transamination Capacity of the three energy systems • You can see from table 3-5 the inverse relationship between the power of the 3 systems and their capacity • Important – All 3 energy systems are always being used to some extent, even at rest Capacity vs Power Athletic performance • Note the triphasic nature of the graph • Different events may select out participants based on how they store energy • Note similarity between genders immediate Non-oxidative Oxidative Enzymatic regulation Enzymatic regulation • • • • Substrate: reactant Active site: where substrate attaches Enzyme-substrate complex Conformation – Can be changed by co-factors (modulators), which affect enzyme-substrate interaction and rate of reaction • Modulators (alter the Rx rate) – Can increase reaction rate (stimulators) • ADP, AMP, Pi – Slow reaction rate (inhibitors) • ATP Enzymes 2 • Modifaction by modulators called “allosterism” (bind to specific site and either inc/dec Rx rate) – Common allosteric modulators • Add or remove Phosphate ion (Pi) – Kinases and phosphatases • Alters rate of enzymatic reaction • Vmax: maximum rate of enzymatic reaction • KM; Michaleis-Menton constant; substrate concentration that gives ½ Vmax Hexokinase: phosphorylates glucose in muscle Glucokinase: phosphates glucose in liver Changes in energy state • Note that ATP is relatively wellmaintained • PCr begins to get depleted during high intensity work • ADP, AMP, Pi change as would be expected from signals of intracellular energy demand Chapter 4 Basics of metabolism • Metabolism: – Sum total of all chemical processes within an organism; produces heat. Why? – Metabolic rate: can be measured as heat production – O2 consumption provides for almost all of our metabolic needs, so Vo2 provides a very good index of metabolic rate – High Vo2 means high metabolic capacity Energy transduction • Conversion of energy from one form to another – 3 major types of interconversions • Photosynthesis • Cellular respiration • Cell work – Photosynthesis: plants • Sunlight + 6 CO2 + 6 H2O → C6H12O6 + 6O2 – Cellular respiration: non-plants • C6H12O6 + 6O2 → 6CO2 + 6 H2O + energy – Cell work (ATP used) • Mechanical, synthetic, chemical, osmotic and electrical Metabolism and heat production in animals • • • • Living animals give off heat Metabolism is functionally heat production Calorie: heat required to raise 1 gram water 1 °C Kilocalorie: what is commonly referred to as a calorie Calorimetry • Direct calorimetry – Place entire animal in calorimeter – Measure heat production • Indirect calorimetry – Measure oxygen consumption – Easier Indirect calorimetry • Simple, measures Vo2 and Vco2 • Allows work to be performed while obtaining index of metabolic rate • Gives a good index of “fitness” Steady state • Note how it takes a while for caloric output to stabilize during a certain workload • This stable area is called steady state • To calculate energy expenditure, steady state must be achieved Concept of respiratory quotient/respiratory exchange ratio • Ratio of Co2 produced (Vco2) to O2 consumed (Vo2) • If measured at the cellular levels: RQ • If measured at the mouth: RER • Also RER can go above 1.0, RQ cannot • Why? Complete oxidation of glucose C6H12O6 + 6O2 → 6CO2 + 6H2O + 36 ATP Complete oxidation of palmitate (16C fatty acid) C16H32O2 + 23O2 → 16CO2 + 16H2O + 129 ATP Indirect calorimetry • Couple reasons – With pure glycolysis, RQ or Vco2/Vo2 is 1.0 – However, when measured at the lung (RER), additional Co2 production from acid buffering reactions must be factored in • Buffering of lactic acid – HLA↔H+ + La– H+ + HCO3- ↔ H2CO3 – H2CO3 → H2O + CO2 • C6H12O6 + 6O2 ↔ 6H2O + 6CO2 • H+ + HCO3- ↔ H2CO3 → H2O + CO2 • This extra CO2 is called “non-metabolic” CO2