KIN 336 MUSCLE EXAM

Muscle characteristics

Excitability: neurons and muscle cells, respond to stimuli by producing action potentials

Contractibility: ability muscle contract forcibly when stimulated, generates tension and possibly movement

Extensibility: ability muscle stretch without being damaged

Elasticity: ability to return to length/shape

Arteries/veins → muscle

Arteries/veins run parallel surface of muscle

Arterioles lead to capillary networks which surround each fiber → run parallel to muscle fibers

Increased surface area for diffusion

• Greater elasticity of microcirculation

during stretching and contraction

Muscle structure

Epimysium → Muscle

• Bundle of fascicles

Fascicle is a bundle of muscle fibers

Perimysium → Fascicles

• Bundle of Muscle Fibers

Endomysium → Muscle Fibers

• Muscle cell

• Contains myofibrils

Myofibrils

• Contractile element (7000-8000) -responsible for contraction

• Composed of myofilaments, Sarcomeres

Myofilaments

• Contractile proteins

• Thick- myosin

• Thin- actin, tropomyosin, and troponin

Muscle fibers

Sarcolemma: plasma membrane of muscle fiber

• Surrounds muscle fiber and regulates entry and exit of materials

Sarcoplasm: cytoplasm of muscle fiber

• Site of metabolic processes for normal muscle fiber activities

Sarcoplasmic reticulum: smooth endoplasmic reticulum in muscle fiber

• Stores Ca+2 needed for muscle contraction

Terminal cisternae: expanded ends of sarcoplasmic reticulum, in contact with transverse tubules, site of Ca2+ release

Triad: 2 terminal cisternae + t-tubule

Transverse tubule: extension of the sarcolemma into the sarcoplasm, wrapped around myofibrils

• Quickly transport a muscle impulse from the sarcolemma throughout the entire muscle fiber, Action potentials propagate through the muscle fiber via T-tubules.

Sarcomere

Sarcomere:

Myosin:

• Thick

• Motor protein

• Composed of myosin tail (heavy chains)

• Two globular heads (light chains)

• Has an actin-binding site and ATPase

Actin

• Thin

• Double stranded binding site for

myosin

• Individual actin molecule: G actin

• G actin (individual actin protein molecule) links together: F actin (strand of G actin molecules)

• Tropomyosin: each strand covers

binding site on 7 actin

• Each tropomyosin has 1 troponin

which contains the binding sites for

Ca++

Titin:

• Largest protein in our bodies

• Is found in cardiac, skeletal muscle

fibers

• Acts like a giant spring for passive force

• Tethers the myosin filament within

the sarcomere

• spring stretching across Sarcomere connecting myosin to z disk, when muscle is stretched titin stretches and springs back when stops

• Source of much of the passive force (force produced when muscle is stretched without actively contracting)

in skeletal muscle, if you stretch relaxed muscle it resists being stretched, titin helps create that resistance

• Is the major mechanism for the

Frank-Starling mechanism in the

heart (helps heart respond to increased filling)

Excitation Contraction Coupling

Steps:

Neuromuscular junction: Synapse between a  motor neuron and a skeletal muscle fiber, motor end plate and synaptic cleft

1. AP in a somatic motor neuron travels to the NMJ and triggers the release of Ach

2. Synaptic vesicles containing ACh fuse with nerve cell membrane and release ACh into synaptic cleft

ACh binds with receptors on sarcolemma and depolarizes sarcolemma, transferring AP to muscle cell

- Acetylcholinesterase destroys ACh so another AP does not arise unless more ACh is released

3. Action Potential travels down sarcolemma and into the muscle cell via the transverse tubules

4. Depolarization triggers dihydropyridine receptors (DHP) to open Ca+2 release channels called ryanodine receptors

5. Ca+2 is released from the terminal cisternae of the sarcoplasmic reticulum (SR) into the sarcoplasm

6. Ca+2 binds with Troponin, which removes the blocking action of Tropomyosin from the actin binding sites

7. ATP binds to myosin, and is hydrolyzed, giving myosin energy

   -ATP stored on Myosin head and splits to ADP and Pi

8. Myosin attaches to actin, cross bridge

9. ADP and Pi released, myosin cross bridge pivots, pulling thin filaments past thick to center of Sarcomere (powerstroke)

10. New ATP attaches to myosin, detaching from actin ready for next cross bridge

11. If nerve depolarization ceases, Ca2+ is sequestered to SR via SERCa ATPase pumps leading to muscle rest

ECC anatomical

Anatomical components:

Force production in skeletal muscle

• Excitation

• Stimulation of muscle by nerve (Action Potential)

• Spread of Action Potential through muscle cell

• Contraction

• Crossbridge formation

• Power stroke

• Relaxation

Myosin–Actin Interaction Cycle

• ATP binds to myosin → Myosin detaches from actin.

• ATP is broken down (hydrolyzed) → Myosin head becomes energized/cocked.

• Myosin binds to actin → Forms a cross-bridge.

• Power stroke → Myosin pulls the actin filament toward the center of the sarcomere.

• ADP + Pi are released → Myosin remains attached until a new ATP binds.

• A new ATP binds → Myosin detaches, and the cycle can repeat.

• ATP is used when it binds to myosin to cause detachment from actin, and ATP hydrolysis provides the energy to “cock”/energize the myosin head.

Be able to trace cause → effect if one part of EC coupling is disrupted (e.g., NMJ signaling, T-tubule signaling, SR calcium release, calcium reuptake/relaxation).

What causes muscle relaxation

For a muscle to relax, Ca²⁺ must be removed from the cytoplasm and returned to the sarcoplasmic reticulum (SR).

SERCA pumps Ca²⁺ back into the SR
→ The SERCA pump uses ATP to actively transport Ca²⁺ from the cytoplasm back into the SR.

Ca²⁺ leaves troponin
→ As cytoplasmic Ca²⁺ decreases, Ca²⁺ detaches from troponin.

Tropomyosin covers actin binding sites
→ Myosin can no longer bind to actin.

Cross-bridge cycling stops
→ The muscle relaxes.

Be able to explain fatigue mechanisms that include potential disruption in one or more steps of EC coupling (signal → Ca²⁺ release → cross-bridge → Ca²⁺ reuptake)

Signal: NS repeatedly sends signals to muscles, fatigue= weaker/less effective signal which leads to less force

weak signal - muscle dosen’t get as strong of instruction to contract

Ca2+ release: less Ca2+ in sarcoplasm, less to bind to troponin, fewer cross bridges, less force

Cross bridge:

Ca2+ reuptake: muscle has more difficulty returning to relaxed state between contractions, calcium clean up crew slower, calcium stays elevated longer (example: repeated jump squats → muscle doesn’t have as much time to relax and doesn’t reset as efficiently during contractions)

Elastic elements in a muscle

• Elastic energy in the musculotendinous components is increased with a rapid stretch and then stored.

• If a concentric muscle action follows immediately, the stored energy is released, increasing the total force production. (Stretching rubber band, stored energy adds to force once released)

Series Elastic Component (SEC)

• Workhorse of plyometric exercise

• Tendon

• When stretched, creates passive tension and stores

elastic energy that increases the force produced

Parallel Elastic Component (PEC)

• Epimysium, Perimysium, Endomysium, and Sarcolemma (fascial connective tissue)

• Exerts a passive force with unstimulated muscle

stretch

Contractile Component (CC)

• Actin, Myosin

• The primary source of muscle force

during concentric muscle action

isometric contractions? Isotonic contractions?

Isometric contraction = tension ↑, length stays the same

Ex: holding dumbbell still

Muscle ends - fixed → neither end of muscle moves

Contractile elements: shorten

Elastic elements: stretch

• The muscle's contractile elements (actin/myosin) generate tension.

• The elastic elements stretch, but the muscle as a whole doesn't change length.

Think: muscle is pulling, but nothing moves.

Isotonic contraction = muscle length changes while tension is maintained

Example: curling dumbbell upward

Initial phase ( initially muscle has to build enough tension to deal with elastic elements)

Contractile: shorten

Elastic: stretch

Muscle ends: fixed temporarily

Elastic tension= load (muscle can move the load)

Contractile: shorten

Elastic: shorten

Muscle ends: move

• First, the elastic elements become stretched/tensioned.

• Once enough tension is developed, the muscle can change length and move the load.

• Concentric: muscle shortens.

• Eccentric: muscle lengthens while producing tension.

Muscle twitch

Single, rapid contraction and relaxation cycle in a muscle fiber resulting from a single action potential

Three phases:

Latent Period

• brief delay after the stimulus is applied,

during which excitation-contraction

coupling occurs (no visible contraction yet) → AP, Ca2+ binding troponin

• Contraction Phase

• muscle fiber generates tension as actin and

myosin filaments slide past each other → crossbridge

• Relaxation Phase

• muscle tension decreases as Ca+2 return to

the SR

Motor Unit: a group of

muscle fibers innervated by

a single motor neuron

• Smallest Functional unit of

muscle

• ALL fibers in a motor unit are

of the same type

• ALL fibers in a motor unit

contract together when the

brain ‘recruits’ the motor unit

All or none

Applies to the motor unit/fibers being recruited

A whole muscle can produce different amounts of force because brain can recruit:

• few motor units- small force

• More motor units → more force

• Many motor units - large force

Each recruited motor unit follows all or none principal

Muscle twitch distinguishing characteristics

Not every twitch looks the same even when muscle fiber reaches threshold

• peak force

• Time to peak force

Vary in force depending on fiber type and frequency stimuli

Fiber type:

Fast twitch fiber: faster time to peak force, higher force, fatigues more quickly

Intermediate twitch: display in-between characteristics

Slow twitch: slower time to peak force and takes longer, more resistant to fatigue

Frequency stimuli:

1 stimulus → 1 twitch, if you stimulate it again before it has completely relaxed the effects can add together which produces more force

More frequent stimuli → more force → everntually tetanus

Type IIx fast twitch muscle fibers/ fast glycolitic

• high peak force/ specific force

• Fast time to peak force/ shortening velocity

• Larger cross-sectional area, more myofibrils

• Mostly anaerobic

• Fewer capillaries → don’t need as much oxygen

• Less myoglobin (stores oxygen inside muscle cells)

• Smaller and fewer mitochondria (rely more heavily on glycolysis instead of aerobic ATP production)

• Fatigues quickly → designed for short powerful activity

Type IIa fast twitch/ fast oxidative

Intermediate peak force/ specific force

Intermediate time to peak force/ shortening velocity

Oxidative and glycolytic

Intermediate cross sectional

Intermediate capillaries, myoglobin, mitochondria, fatigues resistance

Type I slow twitch muscle fibers/ slow oxidative

Low peak force/specific force

Slow to peak force/ shortening velocity

Smaller, fewer myofibrils

Mostly aerobic

Higher oxidative enzyme activity

more capillaries, myoglobin, larger number and size mitochondria, fatigues resistant

Muscle fiber type determinates

• we can determine fiber type by muscle biopsy

somatic motor neuron that innervates the fiber are primarily determinant of muscle fiber type, particularly size, diameter, conduction velocity

• if a fiber receives slow signaling pattern from slow motor neuron it develops slow twitch characteristics

• If a fiber receives rapid signaling pattern from fast motor neuron it develops fast twitch characteristics

genetic influence

• FT/ST distribution normally distributed in every human 50/50

• Some have more extreme percentage shifts towards one or the other

• More FT→more advantaged speed/power/strength

• More ST→ more advantaged endurance

• Mostly everyone determined at birth

Training effects muscle fibers

Training changes fiber behavior not identity

Endurance Training

• Type I: greater enhancement

• Capillarization, myoglobin, number & size of mitochondria, oxidative enzyme activity

• Type IIa: enhance ST characteristics at expense of FT characteristics (become more slow-twitch)

• Type IIx: decrease in characteristics (become more type IIa)

Speed/Strength/Power

• Type I: small shift toward IIa characteristics

• Type IIa: enhance FT characteristics

• Greater peak force, faster shortening velocity

• Type IIx: enhanced FT characteristics

• Greater peak force, faster shortening velocity under specific training thresholds (need very high intensity training to enhance)

Endurance Training → results in decline in IIx, IIa shifting toward aerobic

Speed/Strength/Power Training → results in small shift of Type I toward Type IIa characteristics, Type IIa IIx, depending on training thresholds

• Traditionally, it was believed that shifts from Type II to Type I were

possible due to influx in capillary density, myoglobin content, and

mitochondrial size, but NOT from Type I to Type II due to differences in

MHC isoforms

• Studies have identified “hybrid fibers” that express more than one

MHC type

• I I/IIa IIa IIa/IIx IIx I/IIa/IIx

+

• Current evidence suggests ability of fibers to shift between hybrid

and pure fibers as well as between slow and fast fiber types

Fiber types→ performance outcomes

Endurance - marathons, distance cycling, hiking : type 1(slow twitch) fibers

Speed/Power- sprints, vertical jump m type IIx (fast-twitch glycolytic)

Both - soccer, basketball, 400m run: type IIa

Characterize a motor unit

A muscle grades the amount of force it produces by recruiting more motor units or increasing the frequency of motor-unit firing

All fibers receive the same AP

All or none

Motor units may vary by

number of motor units in a muscle (muscle needs precise control may have lots (eye muscles have lots of small motor units, each unit controls relatively few muscle fibers which allows for tiny controlled movements ), muscle that mainly does large amounts of force may have fewer (quads, fewer and larger mus, each motor unit can control many muscle fibers ))

and size (ratio of muscle fibers to neuron) means the number of muscle fibers controlled by one neuron (small mu → 1 neuron and 10 muscle fibers, large mu→ 1 neuron and 1,000 fibers (less precise but much greater force))

Extra-occular muscles

• 10 fibers to 1 nerve → low force, high precision, small MU, Force can be changed in small increments

Medial gastrocnemius

• 1900 fibers to 1 nerve → high force, low precision, large MU, Recruit force of many muscle fibers

Three main ways to vary force production by muscles/muscle groups by varying motor unit recruitment patterns:

Increase/decrease the number of motor units recruited (picking up a pencil → few motor units, picking up a dumbbell→ many more motor units)

Increase/decrease the rate of recruitment of motor units

• rate coding: once Mu are recruited process of modulating the frequency of MU stimulation, allows nervous system to control intensity and duration of muscle force

• single stimulation leads to twitch

• If stimuli are repeated frequently, Summation (muscle force adds together when muscle hasn’t fully relaxed) occurs: Speed up →higher peak force of previous twitch

• If repeated fast enough: tetanus (4-5 times twitch force)

• higher firing rate → contractions occurs closer together → more force)

Synchronization of motor unit recruitment

• Refers to the coordinated firing of multiple motor units at the same time

• Crucial in activities that require explosive strength or quick bursts of power

• Further, different motor units are recruited at different times, so as to produce a smoother muscle tension

• Slow vs Fast recruitment? Slow recruits small motor units first, produces fine precise movements and more fatigue-resistant ; fast recruits larger motor units for powerful explosive movements, fatigued more quickly

(motor units contract together → can produce greater force quickly, less synchronization→ contractions are more spread out) ; a sudden explosive jump requires motor units to activate very quickly and more synchronized

EMGs relating to force

EMG measures electrical activity of a muscle

High force demand: more motor units are recruited, rate coding is going to cause higher frequency of firing → going to cause more electrical activity and a higher EMG amplitude

Low force demand: few motor units recruited, rate coding causes motor units to fire at a lower frequency → less electrical activity and a lower EMG amplitude

MU size principle

Force demand: greater loads reach thresholds sooner (when trying to move something heavy NS needs to activate more motor units more quickly), body recruits motor units based on how much force the task requires

Rate of force development: shorter time to produce force, nervous system increases drive and thresholds reached in bursts ( going from no force to a lot of force, brain needs stronger and faster signal, each motor unit has an activation threshold: with slow movement small motor units reach thresholds first and recruitment happens gradually, with force needed quickly nervous system send strong signal and mu reach thresholds rapidly in quick bursts)

ST MU’s have small alpha motor

neurons

• Slower conduction velocity

• Lower threshold of activation

FT MU’s have large alpha motor

neurons

• Faster conduction velocity

• Higher threshold of activation (Needs stronger NS signal)

Motor neuron size (activation threshold) is primary regulator of MU recruitment

• NS recruits MU based on their activation threshold, low force needed: small neuron with low threshold ST recruited, rapid forces strong nervous system drive higher thresholds reached FT recruited quickly (size of motor neuron largely determines how easily that MU gets turned on)

ST MU recruited first (small motor neurons and low activation thresholds easy to activate)

As demand increases recruit larger alpha motor neuron/MU (type 1 → type IIa → type IIx)

Force requirements decline, large FT MU become inactive first (last to contract,first to relax) , smaller ST units can stay active bc still needed for low force

Length-tension curve

• Illustrates how the length of the muscle/sarcomere at the onset of the force production influences the amount of force generated

Length tension curve shows relationship between muscle length and amount of force muscle can produce

• There is an “optimal” region for length where the maximum amount of force is produced (actin and myosin overlap just right, lots of opportunities for myosin to grab onto actin and form cross-bridges)

• Too short – force production decreases (actin filaments overlap too much, cross bridges can’t work as effectively)

• Too long – force production decreases (not enough overlap between myosin and actin)

Less than optimal length: fewer cross bridge interaction=reduced tension development (squeezing at top bicep curl)

Optimal length: maximal cross bridge interaction= maximal tension development (bicep curl)

Greater than optimal length: no cross bridge interaction= no tension development (myosin has nothing to grab onto no cross bridges can form) (if hand is close enough to rope can grab it and produce force if hand too far way no grip no force) (extended arm can’t bicep curl)

FORCE-VELOCITY (LOAD-VELOCITY) RELATIONSHIP

inverse relationship between the force a muscle can generate and the velocity at which it contracts (curling light weight can do it fast curling heavy weight is slower)

• At higher forces (greater load),muscles contract more slowly because more effort is needed to overcome the resistance

• At higher velocities (sprinting), the force muscles can generate is lower because there’s less time to develop maximal force. (Sprinting muscle contracting quickly, because movement so fast less time to develop maximal force)

• At any given velocity, a person with a higher percentage of fast twitch muscle fibers will be able to produce more force than a

  person with a higher percentage of slow twitch fibers.

• As velocity increase, ST fibers cannot contract fast enough to contribute to overall force production → less fiber contributing results in less force

• Power= force x velocity (ability to produce force quickly), power is highest when you have a good balance of force and velocity

Implications: can’t maximize force and contraction speed at same time during a concentric contraction

Limitations: relationship isn’t same for every situation depends on muscle length muscle fiber type type of contraction fatigue

Typically, the peak power output occurs at around 30-50% of an individual’s maximum force and 30-50% of maximum velocity, depending on the specific movement and muscle group.

Sensory receptors

muscle spindles: detect stretch

Golgi tendon organs: inhibit excessive tension

Chemoreceptors and joint receptors: provide feedback to modulate force

Factors determining muscle tension

Total number of muscle fibers contracting

• Recruitment of MU

• Asynchronous activity of MU

Tension within each contracting fiber

• Frequency

• Length-Tension of fiber length

• Demand (Force-Velocity)

• Duration (fatigue)

• Sensory feedback

Connect firing frequency → Ca2+ → cross bridges → force

One twitch= AP, Ca2+ release, cross bridge, force, Ca2+ back into SR and muscle relaxation

Summation- another stimulus before full relaxation, Ca2+ released, Ca2+ still present in muscle, more calcium more troponin binding more cross bridges → greater force

Tetanus= very high firing frequency: continuous actin binding site availability, cross bridges continuously form (example: Holding a heavy grocery bag: need continuous force, biceps can’t just contract once and stop, motor units fire repeatedly at a high frequency, producing a sustained contraction)

Difference between summation and tetanus example: summation→ tapping foot repeatedly (gets some time to relax but before completely relaxed it contracts again), tetanus → holding leg in air (NS has to keep sending signals to quads very rapidly to keep leg up, signals come so quickly muscle doesn’t have time to relax)

Myoplasticity

Adaptation of skeletal muscle to chronic stimuli (Engaging/not engaging in consistent exercise → how tissue responds

Can be negative: Lack of stimulus, insufficient stimulus → maladaptation

• Inactivity → atrophy (decrease in size/function of tissues)

  • Inactivity, aging → sarcopenia

Can be positive: overloaded stimulus → positive adaptation

• exercise → hypertrophy (building muscle)

Muscle protein synthesis

Amino acids present: Leucine (key that opens up muscle protein synthesis)

2 ways:

Mechanotransduction (Load responsive element):

• Lifting a weight → muscle experiences tension → integrins sense tension → mTOR pathway stimulated

Steps:

• High tension → integrin stimulates mTOR pathway

• Activation of mTORC1 → stimulates ribosomal activity → produces protein

• Protein synthesis, cell growth, hypertrophy, decreases protein breakdown

Hormone Regulation: testosterone (Hormone Resoinsive Element)

• testosterone → androgen receptor → moves into nucleus → affects gene activity → increases muscle building signals

Steps:

• androgen receptors move HRC to nucleus

• Gene expression changes, protein breakdown decreases

• Contributes to signaling that supports mTOR activity

• mTORC1 → stimulates ribosomal activity → produces protein

• Protein synthesis, cell growth, hypertrophy, decreases protein breakdown

Muscle atrophy

Injury/immobilization

Microgravity: lack of gravity reduces load on muscle (on earth muscles constantly doing work to stand maintain posture, in space don’t have to support body weight)

• decrease in Type I due to lack of endurance conditions (type I contstantly used for things like walking and standing)

• Catabolic > anabolic (catabolic = breakdown, anabolic = buildup), muscle breakdown > muscle building

• Metabolic changes

Aging

• decrease alpha motor neurons (controls a group of muscle fibers), myelinated nerve fibers (myelin sheath for nerve to travel quickly), increase in size of motor units → motor neuron dies, remaining neuron takes over its muscle fibers → reduces fine motor control

• Decrease capillarizatin (less oxygen supply, decrease ability to support aerobic metabolism)

• Decrease oxidative capacity (ability muscle produce ATP using oxygen)

• Decrease in number/amount mitochondria not quality of mitochondria

• Glucose can’t be used/stored as well due to high insulin resistance

Sedentary lifestyle

Hypertrophy vs hyperplasia

Hypertrophy

• Increased size of muscle fiber

• Muscles get bigger because individual muscle fibers increase in size

• Muscle fibers hypertrophy because strength training stimulates an increase in muscle protein synthesis

Hyperplasia (appears much less important in humans)

Increased number of myofibrils

• Load-induced myofibril split? Very large muscle fiber experiences heavy loading, fiber may split potentially contributing to more fibers

• Proliferation of satellite cells? Satellite cells are muscle stem cells, proliferation of these cells can become muscle cells

Strength training positive adaptations

• increase strength and muscle size (contractile and regulatory proteins)

• Increase size and tensile strength of tendons and ligaments

• Increase bone mineral content (BMC)

• Increase anaerobic biochemical capability

  • ATP, CrP, muscle glycogen, glycolytic enzymes

• Decreased insulin resistance (insulin helps move glucose from blood into cells, glucose used for energy or stored as glycogen)

• Cardiovascular adaptations: BP rises during workouts, heart muscle adapts, increase myocardial wall thickness, improves cardiac output and work capacity at higher intensities

In youth: Children do not have completely developed anatomical or hormonal systems that will result in significant strength and/or mass increases

Laws of Thermodynamics

Energy is neither created nor destroyed

• Conservation of Energy

• Energy is transformed from one type to another

In the body, energy is not “created” but transformed from one type (contained in food) to a form that can be used by the body for useful processes

• Only approximately 25% of this energy is converted to a useful form with most converted as heat

• This heat can be used to maintain appropriate body temp

Why are high-energy phosphates important?

High energy phosphates mainly ATP and phosphocreatine are important because they provide immediate energy for muscle contraction and other cellular processes

Chemical compounds (ex:ATP, glucose, PCr molecules) in the body can store energy in their chemical bonds (like a charged battery)

• Energy transfer in the body can occur by releasing potential energy stored in chemical bonds (chemical energy → mechanical energy)

Ex: ATP → ADP + Pi + energy

ATP

ATP is the common denominator for energy storage and use for all cells in the body

• “Common energy currency”

• Cells depend on a constant supply of energy from ATP

However, there is fairly small amount to be found in the body at any given time

• we must be able to replenish our supply of ATP quickly when it has been used

composed of:

• Adenosine (protein)

• Ribose molecule (sugar)

3 phosphate groups:

• Adenosine + 1 phosphate = adenosine monophosphate

• Adenosine + 2 phosphates = adenosine diphosphate

• Adenosine + 3 phosphates = adenosine triphosphate

Addition of third phosphate group contains the energy stored in this reaction, increasing its potential energy

• Phosphorylation- adding a phosphate group to a molecule

ADP= partially changed batter, adding a phosphate group+ energy= charging it, ATP= fully charged battery

Energy used to add third phosphate is stored in ATP and can later be released when ATP broken down

When ATP goes through a chemical reaction that removes a phosphate group, potential energy stored in that bond is released.

• This energy can then be used by cells of the body for useful work.

When energy needed → ATP→ ADP + Pi + energy (phosphate is removed and the stored energy becomes available)

1. Energy from food makes ATP (phosphate added), when cell needs energy phosphate removed

Enzymes

ATPase breaks down ATP → ADP + Pi + energy

When found in skeletal muscle, the enzyme is called myosin ATPase

Enzymes speed up chemical reactions by lowering the energy of activation needed to initiate the reaction (catalysts)

Grouped by Type:

• Oxidases

• promotes the transfer of a H+ from a substrate to an O2 molecule, forming H2o or H2O2

• Oxidized: remove e- (loss)

• Reduced: add e- (gain)

Loss of electrons - oxidation, gain of electrons - reduction

• Kinases

• Enzymes that catalyze the transfer of a phosphate group from ATP to a specified molecule

Chemical reactions that break down ATP:

Myosin ATPase

• Located on myosin head, ATP is needed not only for force production but also for muscle relaxation

Ion Pumps

Ca++ ATPase

• rapid relaxation of muscle by returning

calcium to the SR

• Na+/ K+ ATPase

• Vital for muscle cell excitability and repeated

contraction

Substrate level vs oxidative phosphorylation

Substrate level: Transfer a phosphate group from a substrate to ADP

• Occurs in cytosol and mitochondrial matrix

• Provides a small amount of ATP allowing cells to generate ATP quickly in the absence of oxygen

Ex: glycolysis → pyruvate kinase adds a phosphate from PEP to ADP → gives ATP and pyruvate

Oxidative: Produce ATP by adding phosphate to ADP using energy derived from a series of electron carriers, with oxygen serving as the final electron acceptor

• Occurs in inner mitochondrial membrane

• Produces the majority of ATP

Difference: substrate - phosphate comes directly from another molecule (small amount ATP, glycolysis and Krebs cycle), oxidative- energy moving through electrons in electron transport chain creates protein gradient. ATP synthase uses that energy adds phosphate to ADP (produces most ATP)

Anaerobic vs aerobic

Anaerobic: oxygen always present but doesn’t require it, metabolic reactions that break down glucose without oxygen, producing lactic acid rather than carbon dioxide and water

does not require oxygen, produces ATP quickly, produces smaller amount, used more during shirt, high intensity activity, glycolysis + ATP-PCr important, example,sprinting heavy lifting

Aerobic: metabolic reactions that take place in the presence of oxygen to convert chemical energy into ATP

requires oxygen, produces ATP slower, produces large amount, used more during longer-duration/lower-moderate activity, oxidative phosphorylation major ATP producing pathway, example jogging walking

muscle have enough oxygen but switch to anaerobic b/c much quicker way to produce energy, determinants are intensity and duration

Immediate (anaerobic) sources

• Creatine Kinase reaction

• Adenylate Kinase reaction

• Cytosol

Nonoxidative Sources

• Anaerobic glycolysis

• Cytosol

Oxidative (aerobic) Sources

• Oxidative phosphorylation

• Mitochondria

3 ATP pathways

All energy systems are active/are used at all times by the body

• There are certain conditions where 1 energy system may be the predominate system to rephosphorylate ATP

• INTENSITY

• DURATION

1. Creatine Phosphate: Phosphagen, ATP-PC, Anaerobic Alactic, Single-step Creatine Kinase and Adenylate Kinase reactions

   • Power, high speeds quickly, consumes fuel extremely fast, Highest Rate, Low Total ATP, dominant during first few seconds maximal activity

2. Anaerobic Glycolysis : Lactic System, Fast/Slow Glycolysis, 10-step breakdown of glucose

   • Not as fast off the line, can maintain a high speed for a little while before a refuel High-Moderate Rate, Moderate ATP

3. Oxidative Phosphorylation: Aerobic System

   • Krebs Cycle and Electron Transport Chain for ATP

   • Not designed for max speed, but can drive for hours on a single tank, Lowest Rate, Highest Total ATP

Creatine Phosphate key characteristics

ATP– The Star Player: Provides energy for muscle contraction

Creatine Phosphate System

• Creatine

• The Quick Responder: Provides rapid energy by helping to quickly regenerate ATP from ADP,

essential during the first few seconds of high-intensity efforts

• Creatine Phosphate (CP)

• The Backup: Quickly regenerates ATP during short, intense activities.

• Creatine Kinase

• The Facilitator: Helps transfer a phosphate from CP to ADP to make ATP.

• Adenylate Kinase

• The Recycler: converts two ADP molecules into one ATP and one AMP, for intense, short

bursts

Anaerobic glycolysis key charcteristics

ATP– The Star Player: Provides energy for muscle contraction

Glycolysis

• Glucose

• The Fuel: The primary molecule broken down for energy

• Hexokinase

• The Starter : gets the play going- Initiates glycolysis

• Phosphofructokinase (PFK)

• The Gatekeeper: controls the Flow

• Pyruvate Kinase

• The Finisher: seals the deal- Catalyzes the final step, producing pyruvate and generating ATP

• Pyruvate

• The Outcome: What glucose is turned into, can go aerobic or anaerobic

• NAD+

• The Uber: Picks up electrons (becomes NADH) to be used later in energy production

• NADH

• The Occupied Uber: Holds and transports electrons for later use in the Electron Transport Chain

• Lactate

• The Byproduct: Formed when oxygen isn’t present but can be reused for energy later

Oxidative phosphorylation key characteristics

Krebs Cycle (Citric Acid Cycle)

• Acetyl-CoA

• The Entry Ticket: The molecule that enters the Krebs Cycle from pyruvate or fat

• NAD+

• The Uber: Picks up electrons (becomes NADH) to be used later in energy production

• NADH

• The Occupied Uber: Holds and transports electrons for later use in the Electron Transport Chain

• FAD

• The Lyft: Transports electrons by turning into FADH2

• FADH2

• The Occupied Lyft: Carries more electrons for the Electron Transport Chain

• CO2

• The Waste Product: Released as energy is produced

Electron Transport Chain

• NAD+

• NADH

• FAD

• FADH2

• Oxygen

• ATP Synthase

• Aerobic

• The Uber: Picks up electrons (becomes NADH) to be used later in energy production

• The Occupied Uber: Holds and transports electrons for later use in the Electron Transport Chain

• The Lyft: Transports electrons by turning into FADH2

• The Occupied Lyft: Carries more electrons for the Electron Transport Chain

• The Final Receiver: Accepts electrons to form water and allow ATP production to continue

• The Closer: Uses the energy from electrons to produce ATP

• The Marathoner: Processes energy with oxygen, providing long-term, efficient energy

Creatine

• “Quick responder”

• Protein that is either consumed in the

diet or synthesized by the liver, pancreas, and kidneys from the amino acids arginine, glycine and methionine

Combines with Phosphate to form Creatine Phosphate

The Backup”

• Breakdown of CP is not used directly to accomplish cellular work, but to rebuild ATP and maintain a relatively constant supply

• 1-Step reaction (immediate)

• O2 not needed for this portion of reaction

• As ATP drops, CrP quickly gives up Phosphate to convert ADP → ATP

• ~10 seconds max intensity, up to 30 seconds

• If recovery, replenished 1-2 minutes

• Cells prevent ATP depletion by reducing CP, other processes for ATP recruited (uses CP to quickly regenerate, as CP becomes depleted glycolysis recruited)

Creatine Kinase reaction, enzyme location

• Creatine Phosphate

• Stored in muscle cells (sarcoplasm) within proximity to muscle contractions

• Creatine Kinase enzyme

• Located in myosin filament and mitochondria

• Sensitive to ADP

How we get ATP from breakdown of phsophate

The facilitator”

• Breakdown of CP is not used directly to accomplish cellular work, but to rebuild ATP and maintain a relatively constant supply

• 1-Step reaction (immediate)

• O2 not needed for this portion of

reaction

• As ATP drops, CrP quicks gives up Phosphate to convert ADP → ATP

• ~10 seconds max intensity, up to 30 seconds

• If recovered, replenished 1-2 minutes

• Cells prevent ATP depletion by reducing

Creatine phosphate + ADP → creatine kinase → ATP + Creatine

Adenylate Kinase reaction + when employed

• “The recycler”

Employee during sustained high intensity exercise when ATP demand very high and ADP accumulating

(ATP already stored → creatine kinase main earlier reaction, CrP depletes → Adenylate kinase

• Emergency back to regenerate ATP during sustained, high intensity by transferring one phosphate from one ADP to another

Have extra ADP lets recycle it: ADP one gives ADP 2 its phosphate which makes 1 ATP and 1 AMP

ADP + ADP → adenylate kinase → ATP + AMP

Adenylate kinase rearranges their phosphates

• Mostly found in fast twitch: used for high-intensity, powerful activities where ATP consumed rapidly

• AMP acts as important signaling reaction: alarm signal for muscles, need more ATP

• ↑ AMP activate AMP-Activated Protein Kinase

(AMPK)

How is creatine phosphate rephosphorylated

Restoration of CrP from Cr occur aerobically

Creatine shuttle shuttles Cr to mitochondria

Resphosphorylated by ATP from oxidative phosphorylation

ATP + Cr → CrP + ADP (CrP stored to be used again)

Process only occurs during recovery or rest after exercise

Creatine Kinase helps rephosphorylize CrP using ATP

CK takes P from ATP, produced by oxidative phosphorylation transfers it to Cr → CrP and ADP

ADP enters mitochondria → ETC, CrP → back to sarcomeres

• located in mostly skeletal muscle, also heart and brain

• Located in sarcoplasm and mitochondria of muscle cells

• Ones in mitochondria → mtCK : facilitate rephosphorylization of CrP

• Very little found in blood normally → exercise induced injury/ soreness → CK leak out into bloodstream from damaged muscle tissue

• Myocardial infarction→ digestive heart cells realease CK into blood

Creatine supplementation

Creatine phosphate can be depleted during high intensity exercise → Muscular fatigue is associated with creatine depletion

Most studies show that short-term loading doesn’t result in an immediate increase in absolute or maximal strength or power But does result in an ability to delay fatigue

• Exert the same force for a longer period of time, e.g. perform more repetitions of a weight training exercise

• Goal of supplementation: “saturation”

Consumption of a Cr supplement results in blood Cr levels rising

Application very specific to strength and power activities, 2-5 g per day, no use if kidney disease/disfunction

Be able to explain why PCr is crucial for very short, very intense efforts and what limits it (availability + rephosphorylation)

CrP muscles emergency ATP reserve

During something like maximal sprint, jump, or heavy lift muscles need ATP immediately

Only have small amount ATP already stored, CrP rapidly regenerates ATP, reaction very fast and doesn’t require oxygen

CrP important for first several seconds of maximal effort

• Limitations:

  limited amount CrP stored in muscles, everntually isn’t enough to keep rapidly regenerating ATP

  CrP rephosphorylization: once use CrP have to recharge it back from creatine into CrP again, produced primarily aerobically which takes time and is primarily restored during recovery

Glucose

Carbs ingested, digestion Catabolizes glucose absorbed into bloodstream then stores in muscle and liver as glycogen, small amount in blood

• Glucagon:↑ blood glucose; glycogenolysis/gluconeogenesis

• Insulin: ↓blood glucose; facilitates glucose uptake/glycogenesis

Glycolysis major functions

Break down glucose and make ATP

Generate pyruvate which can go 1 of 2 directions:

• pyruvate converted to lactate: ATP resynthesis occurs at a faster rate but is limited in duration (fast/anaerobic)

• Pyruvate can be shuttled into mitochondria to undergo Krebs cycle, ATP resyntheisis rate is slower but can occur for longer duration if exercise intensity low enough (slow/aerobic)

GLUT1 AND GLUT4

Both glucose transporters, job is to help glucose get from blood into cells

GLUT1: active all the time, present on cell surface, independent of insulin and contraction

GLUT4: stimulated by both insulin and muscle contraction, not solely dependent, trans located from intercellular space (t-tubules and SR) to plasma membrane

Determining factor fate of pyruvate

Rate of glycolysis relative to mitochondrial oxidative capacity

• exercise intensity relatively low mitochondria has time to process pyruvate from glycolysis (ex:walking)

• Intensity too high mitochondria does not have enough time to process leading to more getting turned into lactate

NAD+ availability/intensity - driven flux supply dictated on demand

• NAD+ needed for glycolysis to continue, not enough NAD+ → pyruvate + NADH → NAD+ + lactate (more pyruvate getting turned into lactate)

Glycolysis 2 phases

Energy investment phase (steps 1-5)

• Prime glycolysis by addition of ATP in 2 different reactions

• Purpose: add phosphate groups to substrate (phosphorylation)

Energy generating phase (steps 6-10)

• Produce 4 ATP (net = 2)

• Also produces 2 NADH

Glycolysis overview

Step 1. Energy investment

Hexokinase breaks down glucose into glucose-6-phosphate and spends 2 ATP (Glycogen skips 1st step only spends 1)

^ Glucose + ATP → G-6-P + ADP

PFK: controls flow glycolysis → high ATP - inhibits glycolysis/slows it, high ADP -stimulates glycolysis, PFK uses ADP from ATP spent to rearrange carbons

Glucose/glycogen then broken down into 2 G-3-Ps (everything happens twice now b/c have 2 molecules)

Step 2: Energy generating

G-3-P converted to higher molecule, during: NAD+ picks up H+ ions released, becomes NADH and goes to electron transport train (or NADH reoxidated to NAD+ (pyruvate → lactate)

Now higher G-3-P molecule adds phosphate to ADP (happens twice) → 2 ATP produced (substrate-level phosphorylation)

Eventually pyruvate Kinase adds molecule with ADP (PEP + ADP → 2 pyruvate + 2 ATP), pyruvate either combines with NADH to form lactate or goes to mitochondria for Krebs Cycle

Final products: 4 ATP, 2 NADH, 2 pyruvate

Glycolysis main takeaways

1. NET ATP

Glucose: in blood then enters muscle cell, cell has to add phosphate so can go through glycolysis, hexokinase (activated by high levels of glucose, limited by high levels of ATP) uses ATP to phosphorylize glucose → glucose-6-phosphate: costs 1 ATP + 1 ATP spent later, spend 2 ATP → glycolysis: produce 4 ATP, NET = 2 ATP

Glycogen: stored in muscle cell, already is phosphorylized so skips 1st ATP spending step, only spends 1 ATP → glycolysis → 4 ATP, NET= 3 ATP

2. Rate control

Phosphofructokinase (PFK): gatekeeper -controls flow of glycolysis (high ATP inhibits glycolysis, high ADP stimulates glycolysis)

• PFK senses muscles energy status and decides do we need to make more ATP, if exercising hard have lots of ADP and AMP increasing → PFK speeds up glycolysis so more ATP produced

3. ATP generation (energy generation phase):

Glucose molecule split into two 3-carbon-molecules, so ATP-producing reactions happen twice → produces 2 ATP

NAD+(empty uber) accepts H+ molecules released, NAD+ → 2NADH (occupied uber) goes to ETC

Pyruvate Kinase adds G-3-P and ADP makes 2 ATP and 2 pyruvate (pyruvate can go aneorobic or aerobic)

4. NAD+ regeneration

NAD+ keeps picking up H+ → NADH, eventually runs low

NAD+ needed for glycolysis to continue

Pyruvate + NADH → Lactate and NAD+ (glycolysis can continue)

5. Low ph

During intense exercise muscle produces a lot of H+ which lowers ph

When exercise is high intensity and glycolysis is being used at a high rate: Glucose and/or glycogen is used at a high rate, Lactate is produced at a high rate , Lactate concentration increases in the muscle/muscle cell, There is an associated decline in cellular pH • Decrease key enzyme activity

• Myosin ATPase, CK, PFK, etc.
• Decrease Ca++-Troponin binding, crossbridge formation = less force

Extra bicarbonate in blood can lower H+ and pH lowers

Cori cycle

Lactate formed from pyruvate can be transported in the blood to the liver, where it is converted to glucose

Liver is a recycling center

Glucose → lactate in the muscle then gets sent out into the blood to the liver, lactate→ glucose in the liver then gets sent out into the blood into muscle which uses the glucose again, cycle repeats

Not gaining more energy, recycling carbon not creating free ATP

Support system that is costing:

Muscle gains 2 ATP from glycolysis

Lover spends 6 ATP to remake glucose

Negative energy balance and not energy efficient but tradeoff: maintain blood glucose, clear/recycle lactate, support continued glycolysis

Reduction of pyruvate to lactate

NAD+ must be avalaible for glycolysis

Rate of glycolysis → FAST: Reduce to Lactate

• Lactate Dehydrogenase converts pyruvate to lactate

Pyruvate accepts 2 H+ from NADH + H to form lactate (reduction b/c gaining electron), NADH oxidized to NAD⁺

• Regeneration of NAD⁺ can be reused

Cori Cycle occurs and glycolysis can continue

Reaction that allows pyruvate to enter Kreb’s cycle

2 pyruvate from glycolysis

Pyruvate has 3 carbons

1. One carbon is removed by Pyruvate Dehydrogenase (PDH), → 2C + C02, C02 exhaled through lungs

2. Energy captured as NADH (when ^ reaction occurs NAD+ picks up high energy electrons, NAD+→ NADH)

3. Remaining 2 carbon molecule acetate attaches to coenzyme A → Acetyl-CoA enters Krebs Cycle (key/ entry ticket)

Kreb’s cycle purpose

Make ATP by removing H+ from acetyl groups and attaching them to NAD and FAD to feed the ETC (acetyl groups are converted from Carbs, Fats, and proteins

Extracts high energy electrons from acetyl-CoA and load them onto NADH and FADH2 which then take those electrons to the ETC to help make lots of ATP

What does Kreb’s produce with each turn? How many turns per molecule of glucose and what is the yield?

Occurs in the mitochondrial matrix

One turn=processing 1 acetyl-CoA, For each turn cycle produces: 3 NADH, 1 FADH2, 1 ATP, 2 CO2

1 glucose → 2 pyruvate → 2 acetyl-CoA therefore 1 glucose= 2 turns of cycle

Total yield per glucose from cycle: 6 NADH, 2 FADH2, 2 ATP, 4 CO2

What is important of NADH, H+, FADH2

Up to this point 4 ATP from glycolysis and 2 ATP from Krebs cycle have been formed by substrate level phosphorylation, the rest is high energy electrons of NADH and FADH2

FAD transports electrons by turning into FADH2

Important bc they carry high-energy electrons to the ETC. Thise electrons ultimately allow body to make lots of ATP

Electron Transport Train

occurs across inner mitochondrial membrane

1. Complexes:

• Complex I: NADH gives its electrons to complex I, 2 e- offloaded, complex I pumps 4 H+ across membrane

• Complex II: FADH2 gives its electrons to complex II, 2 e- offloaded, complex II pumps no H+ (why FADH2 produces less ATP than NADH)

• Complex III: receives electrons and pumps 4 H+

• Complex IV: pumps 2 H+, gives the electrons to O2, O2 combines with electrons and H+ to form (2) h2o (reason we breath oxygen)

2. NADH: complex I: 4 H+, Complex II: 0 H+, Complex III: 4 H+, Complex IV: 2 H+, FADH2: complex I: 0, complex II: 0, complex III: 4, complex IV: 2

   Total of 10 H+ NADH and 6 H+ FADH (NADH makes more ATP b/c enters at complex I and FADH2 enters at complex II) (more H+ pumped → bigger gradient → more energy available for ATP production)

3. Proton gradient: during ETC more H+ gets pumped into the intermembrane space (outside) than the mitochondrial matrix (inside) which creates proton gradient , energy naturally wants to flow from higher to lower concentration to reach equilibrium, H+ wants to move back in and uses ATP synthase to go into matrix, energy from movement causes ATP synthase to change shape and energy is used to make ADP + Pi + energy → ATP

4. ATP: gradient stores potential energy, ATP synthase channel for H+ to move back in, as flows in energy is released which synthase uses to make ATP

5. Total ATP from NADH and FADH2: NADH (10H+)4 H+ needed per ATP = 2.5 ATP, FADH (6H+) 4 H+ needed per ATP= 1.5 ATP

6. Oxygen purpose: acts as final electron acceptor at complex IV, oxygen combines with electrons and H+ and forms 2 water molecules, water is the end product

Malate-Asparate Shuttle and Glycerol Phosphate Shuttle

Why these important: during goycolysis, glucose broken down in the cytoplasm and NADH produced, NADH in cytosine but ETC in mitochondria, cell uses shuttles to transfer the electrons from NADH cytosol to NADH mitochondria (electrons not NADH itself)

Malate-Asparate:

Electrons enter NADH inside mitochondria and now enter ETC at complex I, result in 2.5 ATP

Most prevalent heart, type I, type IIa fibers: these tissues and fibers rely on oxidative metabolism

Glycerol phosphate:

Cytolistijc NADH gives electrons to shuttle, electrons transferred to FAD producing FADH2, enters at Complex II, results in 1.5 ATP, most prevalent type IIx fibers: very high intensity, fast energy production

Grand total ATP from 1 molecule glucose

30-32 ATP

How does exercise intensity influence appearance of lactate

• when muscle produces lactate it leaves the muscle cell and enters capillaries where it can travel to tissues (heart,kidney,liver)

• The heart and oxidative skeletal muscle prefer lactate over glucose and fatty acids during exercise

• When lactate arrives at heart can convert back to pyruvate using lactate dehydrogenase, that pyruvate can then enter mitochondria to make more ATP, heart can use lactate as fuel

• When arrives at liver can be converted into pyruvate and either send pyruvate to mitochondria or create glucose through glucogenesis (Cori cycle)

As exercise intensity increases so does rate of glycolysis which produces pyruvate, if rate of pyruvate exceeds mitochondrial oxidative capacity more lactate is formed

Low exercise intensity: O2 supply=demand, no lactate produced

Factors influence lactate appearance/dissapearrance

Factors that affect Appearance:

1. Rate of pyruvate (rate of glycolysis)

• Lactate dehydrogenase converts pyruvate to lactate

2. Rate of uptake of pyruvate

• Mitochondria (pyruvate dehydrogenase) how quickly can mitochondria take up pyruvate

3. Capacity of shuttles (NADH → mitochondria)

• Malate-aspartate and glycerol phosphate,

4. Type of LDH Isoform

• M vs H, M tends to produce more lactate, H tissues better suited to use lactate

5. Rate of Lactate to Blood (MCT4)

• Lactate release

Factors that affect Disappearance:

1. Blood lactate concentration → the more lactate in the blood the more that can be taken up and used

2. Exercise intensity → low: oxidative muscles actively using, high intensity: production can exceed removal

3. Endurance training → can increase mitochondrial capacity and blood flow (ability to take up and use lactate)

4. Concentration and activity of MCT1

• Lactate uptake

5. Active Recovery → instead of completely stopping after exercise, light activity can help clear lactate, hard run → easy walk, muscles still receiving blood flow and mitochondria still active so they can take up and oxidize lactate

Lactate threshold

Intensity of exercise in which blood lactate begins to accumulate at a rate that exceeds the rate of lactate clearance (appearance> clearance)

Signals a transition for aerobic to anaerobic metabolism, not the point oxygen runs out, not an off and on switch between aerobic and anaerobic metabolism → both systems always contributing balance just shifts as intensity increases

Produced continuously even at rest cause body always doing some glycolysis, represents a glycolytic flux not oxygen debt,dynamic balance between production Ra and clearance Rd

Core functions: fuel, glucogenic precursor, signal

• Glycolysis → metabolic acidosis, lack of clearence with adversely impact PFK, results in slowing of glycolysis and ATP production

• Lactate rise signals that we are in red zone but it’s the imbalance not lactate itself that limits performance

• Fatigue sets in when the rate of energy supply cannot meet demande, and lactate accumulation is a marker of this imbalance not the direct cause

Lactate threshold specific to performance

Maximal lactate steady state: highest exercise intensity at which lactate appearance =lactate dissapearance (tipping point)

• above MLSS blood lactate rises below MLSS blood lactate stabilizes

• 
  

• Related to performance:

• Lactate threshold important bc helps determine highest exercise intensity before lactate accumulates (once accumulates pH decreases bc pyruvate + ATP → lactate + NAD+)

• Provides personal training marker for endurance, if lactate threshold increases after training, athlete can preform at a higher intensity before accumulation, muscles can develop greater oxidative capacity which makes lactate production=removal

Proper training can improve oxygen delivery and utilization, delaying the rise in lactate at higher work rates and enhancing performance

Lactate Threshold training outcomes:

1. Enhance the body's ability to delay lactate accumulation

2. Utilize it as fuel

3. Clear it efficiently

• * All 3 are critical for improving endurance performance and sustaining higher intensities for extended periods

Protocol:

• Tempo Runs: Exercise at or just below lactate threshold to improve tolerance and clearance

• High-Intensity Interval Training (HIIT): Short bursts of high-intensity work improve mitochondrial density and lactate clearance

• Long, Steady-State Aerobic Training: Builds base aerobic capacity, increasing lactate threshold over time

Lactate threshold training adaptations

1. Increased mitochondrial density

• Delayed lactate production at higher intensities → raising the lactate threshold

2. Improved lactate clearance (MCTs)

• Faster removal and utilization of lactate

3. Improved lactate shuttle efficiency

• Improved lactate recycling and energy utilization

4. Increased lactate threshold power

• Improved endurance performance and ability to sustain higher intensities

5. Improved muscle fiber response

• Better energy efficiency and reduced lactate production at given intensities

Lactate shuttle

A network that moves lactate within and between cells/tissues so it can be used as fuel, recycled into glucose, and act as a signal

Lactate produced by one fiber (IIx), can be transported to an adjacent fiber with ↑ mitochondria (I) without entering blood (neighboring fibers: type II has lots of lactate moves to type I which has lots of mitochondria and can use lactate as fuel) , lactate doesn’t always have to enter bloodstream first

MCTs: move lactate across cell membranes , MCT1: lactate uptake into muscle fibers (type 1), MCT4 lactate out of muscle fibers to blood (type II)

Fuel for oxidative tissues: Heart and oxidative muscle preferentially oxidize lactate during exercise; most lactate disposal is by oxidation.

• Gluconeogenesis (Cori cycle): Liver (and kidney) convert lactate to pyruvate then to glucose then return to blood

Lactate dehydrogenase

Catalyzes the conversion between Pyruvate and Lactate

Isoforms: M form and H form

M Form: (fast twitch muscle)

• high affinity for pyruvate meaning it loves to make lactate from pyruvate, even when there is plenty of oxygen around

H form: ((heart, type I and IIa fibers)

• higher affinity for lactate, meaning it loves to convert lactate back to pyruvate

Critical power

Highest rate at which oxidative metabolism (oxidative phosphorylation) can meet ATP demand without continuous reliance on non-oxidative energy (CrP, glycolysis)

Be able to reason through a scenario where intensity increases and explain:

o why lactate appearance rises

o what “threshold” means conceptually (appearance begins to exceed clearance)

o why threshold/CP matters for performance and pacing

1. Intensity increases → glycolysis increases → pyruvate increases → lactate production increases

2. Body is always producing and cleaning lactate, at lower intensity appearance = clearance, intensity increases appearance exceeeds clearance , threshold is point where lactate begins accumulating bc appearance starts exceeeding

3. Tells u boundary between sustainable and unsustainable exercise intensity (below threshold/CP: oxidative metabolism an meet ATP demand and lactate can be cleared at rate produced exercise sustained for long time, above threshold/CP: ATP demand greater than oxidative metabolism, lactate accumulates, intensity eventually becomes unsustainable

Example:

Runner gradually increasing speed:

Easy jog → lactate production = clearance

Moderate jog → lactate increases but clearance keeps up

Speed increases → threshold neared where lactate begins to exceed clearance

Above threshold/CP: production exceeds clearance eventually runner has to slow down

Identify fat digestion process and absorption

Fat stored in triglycerides ( made up of 3 fatty acid chain and glycerol molecule)

Food goes from Stomach → small intestine

After fat absorbed by intestine, triglycerides cholesterol and fat-soluble vitamins are that are packaged into chylomicrons (fat transport packages)

Chykomicrons enter lacteals in the lymphatic system

Lymph eventually enters blood through thoracic duct

Once chylomicrons are in the blood their triglycerides can be delivered to tissues and the tissues can use fatty acids for energy or store them as fat

Remaining particles go to the liver, liver uses lipoproteins (VLDL, LDL, HDL) to package and transport lipids

Advantages/disadvantages fatty acids for energy

Advantages: high yield ATP

Disadvantages: slow, complicated metabolism

Signals to mobilize stored fatty acids for energy

• fasting

• Exercise

• Stress

• Low insulin

• Increased hormones (catecholamines)

• Increased glucagon

• Increased cortisol

Hormone-sensitive lipase

Splits triglycerides into glycerol and 3 FFA, FFA attaches to albumins transported in blood (lipolysis)

When norepinephrine/epinephrine signal energy is needed, lypolysis (process breaking down stored fat) increases and HSL more active

What 2 factors determine muscle uptake of FFA

FFA= free fatty acids

1. Concentration gradient: difference in FFA concentration between blood and muscle, higher in blood than muscle tends to move in towards muscle, bigger gradient → greater potential FFA uptake

2. Blood flow: determines how much delivered to muscle, more blood flow → more FFA delivered → greater opportunity uptake

Where are fatty acids metabolized

FFAs reaches muscle cell and interacts with fatty acid binding proteins on the sarcolemma

When enters its now in the cytosol FABPs where it travels to the mitochondria through the carnitine shuttle

FFA metabolized in mitochondria but can’t diffuse through membrane

Go through b oxidation in mitochondria

Carnitine Shuttle

Fatty acid attaches to CoA and becomes fatty acyl-CoA but needs help crossing mitochondrial membrane

Carnitine picks it up and it becomes fatty acyl-carnitine and carnitine moves it across mitochondrial membrane

Beta oxidation

Occurs in mitochondrial matrix

Carnitine is removed and fatty-acyl CoA is ready for beta oxidation

B oxidation breaks fatty acids down into acetyle-CoA which goes to the Krebs cycle and NADH + FADH2 wihich goes to the electron transport chain

What does beta oxidation produce per spin

1 FADH2

1 NADH

1 Acetyl-CoA

Process cleaving two carbon units to produce Acetyl-CoA

During b-oxidation fatty acids down is broken down 2 carbons at a time

B oxidation repeatedly cleaves 2 carbon units from a fatty acid chain, each 2 carbon unit forms acetyl-CoA

Remaining fatty acids becomes 2 carbons shorter and continues through another round until fatty acid is fully broken down

Energy produced per spin beta oxidation

14 ATP

1 FADH2: 1.5 ATP

1 NADH: 2.5 ATP

1 acetyl-CoA: 10 ATP ( Krebs cycle 1 turn: 3NADH (2.5) 1 FADH2 (1.5) 1ATP= 10)

Total energy from one complete oxidation of one palmitic acid

106 ATP

•Seven spins (14 ATP x 7) = 98

•Last Acetyl-CoA = 10

•Activation (fatty Acyl-CoA) = -2

Driving forces GLUT4 activation between aerobic and anaerobic exercise

Multiple energy pathways based on duration and intensity, and there is a direct link between PCr and Oxidative phosphorylation

• Cytosol and mitochondria

• Creatine Shuttle

• Mitochondria regulate the rate of ATP resynthesis by oxidative phosphorylation in response to energy demands

As exercise intensity increases from rest to moderate to heavy exercise,progressively greater dependence on CARBOHYDRATE (primarily

muscle glycogen) use

• Increased use of blood glucose with time is facilitated by an increase in GLUT4

• Aerobic

• Gradual, prolonged GLUT4 translocation

• Driven by AMP-activated protein kinase (AMPK) activation due to sustained energy depletion, AMPK promotes GLUT4 movement to membrane

• Slow-twitch fibers for sustained glucose uptake

• Moderate GLUT4 translocation but sustained for a longer period during and after exercise

• Anaerobic

• Rapid and short bursts of GLUT4 translocation

• Driven by muscle contraction and mechanical stress

• Fast-twitch fibers for immediate, high glucose uptake

• Larger, more immediate GLUT4 translocation but with shorter duration

Crossover concept

Intensity determines substrate utilization

Low intensity: more fat, less carbs

As intensity increases so does carbs use

High intensity: more carbs, less fat

The point where carbs use becomes greater than fat use is called the crossover

Endurance training helps muscles become better at using fat, Shifts right you can use more fat at higher intensities, more mitochondria glycogen sparring

Shifts left you rely on carbs sooner , caatecholmines increase carbs utilization, glycogenisis, PFK, lipolysis

Influence activation HSL

Catecholmines influence (norepinephrine and epinephrine) stimulate process

HSL does lipolysis

Carnitine shuttle, transport limited

Shuttle moves long fatty acid chains into mitochondrial matrix

If transport limited: less fatty acid enters mitochondria, less b oxidation, less synergy from fat

Body will rely more heavily on carbs metabolism to meet energy demand

Example after eating meal: blood glucose is high, insulin is high, carnitine shuttle slows, less long fatty acid enters mitochondrial matrix less fat burned because body has plenty incoming glucose

Fat always used to some degree but fatty acids down metabolism increases when carb availability/use is lower

Beta oxidation per cycle and how supports endurance work

A cycle of B oxidation takes a fatty acid and removes 2 carbons, those carbons become acetyl-CoA, along with NADH, FADH2

How supports endurance exercise?

Makes lots of ATP b/c NADH and FADH → ETC and acetyl-CoA→ Krebs , Krebs + ETC= lots of ATP

Fat is ecspecially useful for long-duration endurance exercise because have large stores of fat in body, even though fat produces ATP more slowly you can keep generating ATP from fat for a long time

Crossover concept: % vs absolute energy contribution

what percentage of my energy is coming from fats vs carbs

Low intensity: burn 100 cals total, 70% comes from fat, 30% comes from carbs

Moderate: burn 200 cals, 50% from each (fat percentage went down but actual calories from fat went up)

High intensity: burn 300 cals, 30% comes from fat, 70% comes from carbs

Immediate response to exercise-induced muscle damage

Occurs from intense or prolonged activity, especially:

o Eccentric contractions (e.g., lowering phase of lifting)

o Endurance events (e.g., marathon running)

Immediate response:

• Damage to sarcomeres, Z-line streaming, broadening, A and I band widening

• Organelle damage : mitochondria SR

• Sarcolemma disruption → substances can leak out of Sarcolemma: CK, LDH, hydroxyproline and increases blood levels of all

• Contracture knots (part of muscle that stays abnormally contracted) and loss force production

Delayed response to exercise- induced muscle damage

• force production worsens, slowly returns

• Inflammatory response

• Soreness, stiffness, swelling - DOMS

• Decreases ROM, increase CK in blood

How does repair and regeneration occur

• Inflammatory response clears damaged tissue

• Satellite cells activated → migrate and proliferate

• Form myoblasts → regenerate new muscle tissue

• Stimulates protein synthesis for rebuilding muscle

Adaptations to repeated training bouts

Muscle adapts to repeated eccentric loading, rebuilds with stronger tissue, results in less damage in future loads

Neural theory: CNS adapts and recruits motor units more effectively to exercise demands reducing mechanical stress on fibers, better motor unit recruitment (ex: first time do deadlifts sore, a few weeks later NS better at movement, less damage occurs)

Connective tissue theory: connective tissue stiffens and strengthens (endomysium, perimysium, tendons)

Cellular theory: exercise causes small amounts damage, macrophages clean up damage, satellite cells rebuild tissue

Fatigue and mechanisms of fatigue

Fatigue: inability to sustain a given intensity of exercise

Major contributing mechanisms:

• ATP breakdown faster than muscle can synthesize: depletion of ATP from muscles using rapidly, impaired ability to contract, intensity must be decreased to allow recovery of systems

• Substrate depletion: CrP usually falls in proportion to exercise intensity, muscle glycogen: once glycogen stores exhausted glucose output by gluconeogenesis is the rate limiting step, has to stop exercising if muscle glycogen runs out HITTING A WALL and blood glucose low (low levels→ reduced time to fatigue)

• Accumulation of metabolic end products that inhibit contraction: lactic acid accumulation, acumkukation H+ causes fatigue, PFK inhibited, glycogen breakdown ceases(phosphorylase), H+ inhibits binding site on troponin for Ca2+, Pi interferes with troponin binding site, forms calcium phosphate in SR which lowers Ca2+ release, excess Ca2+ taken up by mitochondria uncouplesmETs wastes O2 without producing ATP

• Failure one or more steps in ECC: something goes wrong between neural signal arriving, muscle contraction occurring, muscle receives less effective activation

• Central nervous system: CNS regulates motor unit recruitment, muscle recruitment and effort perception, group III and IV muscle afferents → sensory nerve fibers, sense metabolic and mechanical changes, trigger inhibitory feedback to spinal cord, metaboreflex: increases HR, BP, ventilation, prioritizes blood flow to vital organs over muscles which leads to muscle fatigue, heavy loading → CNS taxed by sustained high neural drive, motor unit synchronization becomes less efficient, CNS may inhibit output to protect tissue