ATP homeostasis

1. ATP homeostasis

2. Energy systems homeostasis • ATP • Common metabolic intermediate • Powers muscular contraction • Cell work • Well-maintained over wide variations in energy turnover

3. Energy homeostasis • 3 basic energetic systems • Immediate (ATP-PCr) • Non-oxidative: anaerobic glycolysis • Oxidative: oxidative phosphorylation

5. Immediate energy systems Ca2+ • ATP + actin + myosin →Actomyosin + Pi + ADP + energy • ATP +H2O → ADP + Pi • ATP then resynthesized by Creatine kinase and adenylate kinase reactions in immediate energy systems ATPase

6. 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 (5-15s) • These reactions occur in cytoplasm

7. 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

8. Non-oxidative energy sources (continued)

9. 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.

10. Oxidative energy sources Glycolysis→pyruvate

11. 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

12. 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 Transamination glutamate ketoglutarate

13. 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

14. Capacity vs Power

15. Athletic performance immediate • Note the triphasic nature of the graph • Different events may select out participants based on how they store energy • Note similarity between genders Non-oxidative Oxidative

16. Enzymatic regulation

17. 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

18. 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

20. Hexokinase: phosphorylates glucose in muscle Glucokinase: phosphates glucose in liver

21. Changes in energy state • Note that ATP is relatively well-maintained • PCr begins to get depleted during high intensity work • ADP, AMP, Pi change as would be expected from signals of intracellular energy demand

22. Chapter 4 Basics of metabolism

23. 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

24. 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

25. 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

26. Calorimetry • Direct calorimetry • Place entire animal in calorimeter • Measure heat production • Indirect calorimetry • Measure oxygen consumption • Easier

27. Indirect calorimetry • Simple, measures Vo2 and Vco2 • Allows work to be performed while obtaining index of metabolic rate • Gives a good index of “fitness”

28. 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

29. 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

30. 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

31. C6H12O6 + 6O2↔ 6H2O+ 6CO2 • H+ + HCO3- ↔ H2CO3 → H2O + CO2 • This extra CO2 is called “non-metabolic” CO2