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 +H2O → ADP + Pi

• ATP then resynthesized by Creatine kinase and adenylate kinase reactions in immediate energy systems

Ca2+

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 sourcesGlycolysis→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)

ketoglutarate

glutamateDeamination

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 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 4Basics 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 glucoseC6H12O6 + 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