Lecture 4 Flashcards
(22 cards)
Energy “supply vs. Energy “demand”
- different forms of activity require different levels of energy which is supplied in the form of ATP
- ATP is the energy donor for muscle contraction
- cellular levels of ATP are miniscule
- ~6 mmol/kg wet muscle - gone in seconds - during a transition from rest to exercise, demand to resupply ATP can increase >100 fold! (Function of muscle)
- we have well developed systems to resupply ATP - and quickly
No other muscle is allowed to move without ATP
Energy
- energy cannot be created r destroyed; transformed from one state to another
- within muscle, energy is used for:
- Chemical work: synthesis of cellular molecules (form and conserve ATP from food)
- Mechanical work: muscle contraction (power stroke)
- Transport work: maintain concentration of substances in intracellular and extracellular fluids (action potentials, Ca2+ uptake)
Energy in metabolism
We can divide metabolic pathways into 2 broad classes:
- Those that convert substrates (fuel) into energy (catabolic)
- put ATP back together
- need for movement
Fuels (carbohydrate, fats) —> (catabolism) CO2 + H2O + useful energy
- Those that use energy to produce substrate (anabolic)
- produces substrates that store energy
- at rest
- not talking much about this in class
Useful energy + small fuel molecules —> (anabolism) —> complex fuel molecules (protein, fats)
Substrate = starting material of chemical rxn
Product = compound obtained at completion of rxn
Anabolism (endergonic) - building block precursors and ATP equal synthesized end products and ADP + Pi
Catabolism (exergonic) - carbohydrates, fats, proteins + O2 and ADP + Pi equal H2O + CO2 and ATP
Controlling Rate of energy Production
Energy released at controlled rate based on substrate availability and enzyme activity
- mass action effect - more substrate = faster rate; more product = slower rate - enzyme effect - lowers activation energy for a chemical reaction; more enzyme or increased enzyme activity = faster rate of product formation (-ase. All enzymes end in -ase)
These both control the rate of energy production
** chemical rxn occurs only when they have sufficient initial energy (activation energy) to start a rxn or chain of rxns
Enzyme = biological “catalysts”; proteins that help speed up metabolism or the chemical rxns in our bodies; they act like a “dimmer” switch
Noncatalyzed (o enzyme present)
- Phosphocreatine is released, and creates a large activation energy. Not the best
Enzyme-catalyzed (with créatine kinase)
Phosphocreatine is released and there is a small activiation energy. Better
Energy substrates
- fuel sources that we can convert to energy through cellular processes
- body stores of fuel:
- carbohydrate, fat, and protein - breakdown of these stored macronutrients provide energy to resynthesize ATP directly but mostly provide substrates (ex. Pyruvate, acetyl coA, coenzymes) that can contribute to resynthesize ATP through the process of “oxidation”
- fat (triglycerides)
- efficient substrate, efficient storage, slow rate of energy production
- 9.4 kcal/g (6,000+ g stored) - carbohydrates (glucose, glycogen)
- less efficient substrate, less efficient storage, high rate of energy production
- 4.1 kcal/g (~600 g stored)
Location - g - kcal
- carbohydrate
Liver glycogen - 110 - 451
Muscle glycogen - 500 - 2050
Glucose in body fluids - 15 - 62 - fat
Subcutaneous and visceral - 7800 - 73320
Intramuscular - 161 - 1513
Total: 7,961g - 74,833kcal
Note. These estimates are based on a body weight of 65 kg (143lb) with 12% body fat.
Energy source of Human Muscle
- adenosine triphosphate (ATP) breakdown provides the required energy for all muscle cell functions:
ATP + H2O —> (ATPase) —> ADP + Pi + Energy (-7.3 kcal/mol or -30.5 kJ/mol)
- referred to as “hydrolysis” reaction as chemical bonds of the molecule are broken through the addition of water
- breaking of these chemical bonds releases energy
What we need to move the body
Consumers of ATP within the muscle fibre
- Myosin ATPases ~70%
- Ca2+ ATPases ~25-30%
- Na+ -K+ ATPases ~ <5%
All of these contribute to energy “demand”
Skeletal muscle
Muscles fibre
- myofibril
- cytoplasm
- mitochondria
Muscle fibre process
Myosin head -ATP = ADP + Pi
Sarcoplasm moves by product (waste) away from muscle
Muscle ATP store and Breakdown Rates
ATP store: ~6 mmol ATP/kg wet muscle
Exercise type - ATP breakdown rate - Time to complete ATP depletion
Heavy aerobic exercise - 0.4 mmol/kg/sec - 15s
Severe aerobic exercise - 1.0 mmol/kg/sec - 6s
“All-out” sprint - 3.7 mmol/kg/sec - <2s
It is obvious that skeletal muscle metabolism must immediately resupply ATP!
Sources of ATP Resynthesis During “All-out” Exercise
ATP is stored in limited quantities and depletes rapidly (if we only relied on stored ATP we would be exhausted in seconds!)
Kcal/min —> Joules/sec (or Watts) = 4148J/kcal* 0.0166 min/sec* 0.25 [efficiency of converting chemical energy to mechanical work]
3 minute max power cycling
- after 2 sec no ATP left
- you’ll be exhausted
How do we resynthesize ATP?
Synthesis of ATP from by-products (“lending” energy)
ADP (phosphorylating) + Pi + energy —> (ATP synthase) —> ATP + H2O (via phosphorylation)
Can occur in either absence or presence of oxygen
Anaerobic
- “Non-oxidative” energy sources:
- Phosphocreatine
- Glycolysis/Glycogenolysis
ATP resynthesized through non-oxidative processes referred to as “substrate-level” phosphorylation
- in the cytosol “Sarcoplasm”
Aerobic
- “oxidative” energy sources
- citric acid cycle/electron transport
- fatty acids from beta-oxidation
ATP resynthesized through oxidative processes referred to as “oxidative” phosphorylation
- in the mitochondria
Non-oxidative Contributors to Energy Supply
- Stored adenosine triphosphate (ATP)
- Stored Phosphocreatine (PCr)
- Glycolysis/Glycogenolysis (Glycolysis) - sugar
Phosphocreatine
ATPase
ATP + H2O <—> ADP + Pi + Energy
ATP synthase
Créatine Kinase PCr + H+ <—> Cr + Pi + Energy
Energy liberated from hydrolysis (splitting) of PCr, rebonds ADP and Pi to form ATP:
- substrates can become products and vice versa (reversible)
PCr + H+ + ADP <—> ATP + Cr + H2O + Energy
Créatine kinase
When ATP levels decrease (ADP increases), CK activity increases
When ATP levels increase, CK activity decreases
Sources of ATP resynthesis during “all-out” exercise
PCr can resynthesize ATP but it too is stored in limited quantities and depletes rapidly (if only relied on stored ATP and PCr we would be exhausted in 20s or less!)
- after 30sec no ATP or PCr left
- has to be something that helps me continue
Exhausted after 30sec
Glycolysis and Glycogenolysis
Uses glucose or glycogen as its substrate
- must convert to glucose-6-phosphate
- costs 1 ATP for glucose, 0 ATP for glycogen
Pathway starts with glucose-6-phosphate and ends with pyruvate:
- 11 (glucose) or 10 (glycogen) enzymatically controlled rxns
- ATP yield: 2 ATP glucose (2 ATP are used in this process); 3 ATP glycogen (1 ATP is used in the process)
Glucose starts at 1 and glycogen starts at 2
1. Hexokinase
2. Glucose-6-phosphate isomerase
3. Phosphofructokinase
4. Aldolase
5. Triosephosphate isomerase
6. Glyceraldehyde-3-phosphate dehydrogenase
7. Phosphoglycerate kinase
8. Phosphoglyceromutase
9. Enolase
10. Pyruvate kinase
Glucose + 2ADP + 2Pi + 2NAD+ —> 2 pyruvate + 2ATP + 2NADH + 2H2O + 2H+
Glycogen + 3ADP + 3Pi + 2NAD+ —> glycogen + 2 pyruvate + 3ATP + 2NADH + 2H2O + 1H+
Pyruvate process
Found in the cytosol
Glycogen and glucose start then go to —> G-6-P —> ADP to ATP —> NAD+ to NADH —> PYRUVATE (too much - produces lactate, slows down ATP production)
- inhibits the production when too much pyruvate is produced
After you produce pyruvate there’s a reversible rxn where NADH also produces NAD+
- lactate <—> pyruvate
Lactate formation
Convert pyruvate to lactate to prevent inhibition of glycolytic flux by accumulation of pyruvate (mass action effect)
2 Pyruvate + 2NADH (decreases production of produce/ATP) + 2H+ <—lactate dehydrogenase—> 2 lactate + 2NAD+ (substrate for glycolysis)
Sources of ATP resynthesis during “all-out” exercise
Glycolysis/glycogenolysis contributes to ATP resynthesis requirements but has a low ATP yield (if we only relied on stored ATP, PCr and Glycolysis/glycogenolysis we would be exhausted within ~2 min or less!)
Glycolysis/glycogenolysis is what allows us to exercise for longer
- exhaustion begins after 135sec (more than 2 min)
contributors to energy supply
- Stored adenosine triphosphate (ATP)
- Stored Phosphocreatine (PCr)
- Glycolysis/Glycogenolysis (Glycolysis)
- Oxidative Phosphorylation (Oxidative)
Can’t maintain power for long periods of time
Sources of ATP resynthesis during “al-out” exercise
Oxidative phosphorylation can sustain ATP resynthesis requirements indefinitely (if we only relied on stored ATP, PCr and Glycolysis/Glycogenolysis we would be exhausted within 2 min or less!)
With oxidative phosphorylation we have no exhaustion!
“Demand” vs “sources of supply”: 30s Wingate
Biopsy
Trial 1 - 30s
Trial 2 - 15s
Trial 3 - 6s
ATP demand “turnover rate”
- shift in metabolic pathways
- rest - 6s
- 6 - 15s
- 15 - 30s
Métabolite changes - from biopsies
PCr - provides most of the energy in first 6s
Glycolysis/glycogenolysis - most in the first 6-15sec
Oxidative phosphorylation - used the most in 15-30sec
