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 ATP + actin + myosin →Actomyosin + Pi + ADP + energy ATP +H 2 O → ADP + Pi ATP then resynthesized by Creatine kinase and adenylate kinase reactions in immediate energy systems Ca 2+ ATPase

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

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 –C 6 H 12 O 6 + 6O 2 → 6CO 2 + 6H 2 O + 36 ATP Complete oxidation of palmitate (16C fatty acid) –C 16 H 32 O O 2 → 16CO H 2 O 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 (NH 2 group removed or converted to something else) ketoglutarate glutamate Deamination 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

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 K M ; 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 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

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 –O 2 consumption provides for almost all of our metabolic needs, so Vo 2 provides a very good index of metabolic rate –High Vo 2 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 CO H 2 O → C 6 H 12 O 6 + 6O 2 –Cellular respiration: non-plants C 6 H 12 O 6 + 6O 2 → 6CO H 2 O + 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 Vo 2 and Vco 2 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 Co 2 produced (Vco 2 ) to O 2 consumed (Vo 2 ) 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 ATP

Indirect calorimetry Couple reasons –With pure glycolysis, RQ or Vco 2 /Vo 2 is 1.0 –However, when measured at the lung (RER), additional Co 2 production from acid buffering reactions must be factored in Buffering of lactic acid –HLA↔H + + La - –H + + HCO 3 - ↔ H 2 CO 3 –H 2 CO 3 → H 2 O + CO 2

C 6 H 12 O 6 + 6O 2 ↔ 6H 2 O + 6CO 2 H + + HCO 3 - ↔ H 2 CO 3 → H 2 O + CO 2 This extra CO 2 is called “non-metabolic” CO 2