Kin 310
Exercise/Work Physiology
• Office hours - K8621
• W 10:30-12:20
– or by appointment (ryand@sfu.ca)
• class email list
– announcements, questions and
responses
– inform me of a preferred email account
• class notes will be posted on the web
site in power point each week
– can be printed up to six per page
• lecture schedule along with reading
assignment on web site
• www.sfu.ca/~ryand/kin310.htm
1
Overview
• Discussion of the physiological basis of
exercise and work
• Cellular bioenergetics
– Providing ATP to meet demand
• Cardiovascular and respiratory
compensations and capacities
– Limitations and adaptations to training
• Molecular level adaptation
– activity changes the cellular environment stimulating adaptation to better meet demand
• Fatigue - inability to sustain activity level
– description of fatigue in the CNS, the
neuromuscular junction and the muscle cell
• Ageing - change in physiological capacities impacts of disease and activity level
• Assessment of work load and physical
capacity for exercise and work
• Exercise and the Environment
– Heat and barometric pressure can create
additional demands on physiological systems
2
Energy Sources and
Recovery from Exercise
• Ch 2 Foss and Keteyian - Fox’s
Physiological basis for Exercise and
Sport- 6th edition
• all human activity centers around the
ability to provide energy (ATP) on a
continuous basis
– without energy cellular activity would
cease
• Main sources of energy
– biomolecules - carbohydrate and fat
– protein small contribution
• lecture will review metabolic
processes with an emphasis on
regulation and recovery
3
Energy
• Energy - capacity or ability to
perform work
• Work - application of a force through
a distance
• Biological work - transport,
mechanical and chemical work
• Power - amount work performed
over a specific time (rate of work)
• Transformation of energy - forms of
energy can be converted from one
form to another
– chemical energy in food is transformed
into mechanical energy of movement or
other biological work
– Biological energy cycle
4
ATP - adenosine tri-phosphate
• Energy harnessed from molecular
bonds in biomolecules – used to resynthesize ATP - Fig 2.2
• only energy released from ATP can
be utilized to perform cellular work
– ATP in solution represents immediate
source of energy available to muscle
• enzyme (eg. ATPase) break high energy
bonds between phosphate groups
– Forming ADP + Pi + energy
• Energy used to do biological work
– Eg Calcium ATPase, myosin ATPase
• Reaction is reversible (reform ATP)
– CP -creatine phosphate (phosphocreatine)
• Enzyme CK - Creatine Kinase
– Kinases (eg glycolysis)
– oxidative phosphorylation
• form NADH, FADH2 then form ATP
5
Sources of ATP
• Limited quantity of ATP available
– constant turnover (re-synthesis)
- requires energy
• 3 processes - use coupled reactions
• ATP-PC system (phosphagen)
– energy for re-synthesis from CP
• Anaerobic Glycolysis
– ATP from partial breakdown of glucose
• Limited quantities of glucose
– absence of oxygen
– generates lactate as end product (*pH)
• Aerobic System
– requires oxygen
– oxidation of carbohydrates, fatty acids
and protein
– Krebs cycle and Electron Transport
6
Anaerobic sources
• ATP -PC system (fig 2.4)
– high energy phosphates
• energy in CP bond is immediately
available
– as ATP is broken down it is
continuously reformed
– ADP + PC(Creatine Kinase) -> ATP
– ADP + ADP (myokinase) -> ATP
• CP reformed during recovery
– from ATP formed through aerobic
pathways
• Table 2.1 - most rapidly available
fuel source - very limited quantity
– Depleted with 10 seconds of maximum
activity
– Recovers quickly
7
Anaerobic Glycolysis
• Incomplete breakdown of glucose or
glycogen to lactate
• 12 separate, sequential chemical
reactions
– breakdown molecular bonds
– couple reaction to synthesis of ATP
– yields 2 (glucose) or 3 (glycogen) ATP
• Rapid but limited production
– Limited glycogen stores
– lactate accumulates -> acidity -> fatigue
- unable to sustain demand
• PFK - phosphofructokinase
– rate limiting enzyme- slow step in
reaction - inhibited by acidity
• Table 2.2
8
Anaerobic Glycolysis
• Pyruvate is final product of glycolysis
• pyruvate is converted to lactate when
aerobic ATP production can not meet
demand for ATP utilization
–
–
–
–
–
Inadequate O2 delivery (or high demand)
enzyme LDH - lactate dehydrogenase
Redox reaction (Fig 2.6)
*frees up NAD+ required in glycolysis
Allows rapid production of ATP through
glycolysis - until acidity shuts it down
• summary fig 2.7
• glycogen - endogenous fuel
– within muscle
• glucose - exogenous fuel
– comes from blood glucose, released from liver
glycogen
9
Aerobic Sources of ATP
• Acetyl groups - 2 carbon units
– formed from pyruvate and from Beta
oxidation of free fatty acids
• NAD and FAD - electron carriers
– become reduced when biomolecules are
oxidized - form NADH, FADH2
– carry these hydrogen atoms to the
electron transport chain
– donated and passed down chain of
carriers to form ATP
• Oxidative - phosphorylation
• oxygen is final acceptor of
hydrogen, it is reduced to H2O
• occurs in mitochondrial membrane
system - cristae
10
Krebs Cycle
• Fig 2.12 - Krebs Cycle (Citric Acid cycle)
• Key regulatory enzymes
– ICDH(Iso citrate De-hydrogenase), CS (citrate
synthase), KGDH (alpha ketoglutarate DH)
– NADH - inhibits enzyme activity
• High NADH - indicates ETC is behind in
utilizing NADH already produced
– Availability of ADP also regulates
Krebs cycle activity
– ADP and NAD+ are needed for
reactions to occur
• CO2 produced as molecules are
oxidized ( H atoms are removed)
• Krebs Cycle - produces
– (per acetyl group-2 Carbons)
– 1 GTP (ATP equivalent)
– 3 NADH and 1 FADH2
11
ETC
• Electron Transport Chain (ETC)
– H atoms passed down series of
electron carriers by enzymatic
reactions coupled to production of
ATP
– oxidative phosphorylation
• each NADH - yields 3 ATP
• each FADH2 - yields 2 ATP
• for process to continue, must
liberate NAD+ and FAD+ – Process requires oxygen
12
Aerobic Glycolysis
• With sufficient oxygen pyruvate
moves into mitochondria
– Monocarboxylate transporter
– law of mass action
• 1 mole glycogen • glycolysis
– 2 moles pyruvate ; 3 moles ATP
– 2 moles NADH (6 moles ATP after ETC)
• Krebs - per pyruvate molecule
– 4 moles NADH (one from PDH)
• 12 ATP
– 1 mole FADH2
• 2 ATP
– 1 GTP
– Multiplied by 2 = 30 moles of ATP
• 39 ATP per mole of glycogen
13
Fat Metabolism
• Fat and Protein only oxidized
– No anaerobic metabolism
• Fatty acids - 16-18 carbon units
– acetyl groups (2 carbons) broken off
chain to enter Krebs cycle one at a time
• Beta oxidation Fig. 2.15
– uses 1 ATP for first two carbons only
– produces 1 NADH and 1 FADH2
• acetyl co-A through Krebs/ETC
– Yields 12 ATP
• total of 16 ATP for first acetyl group
– 17 for each remaining acetyl group
– last acetyl group only 12 ATP- as it is
not produced by beta oxidation
• 1 mole of palmitic acid-138 of moles ATP
• Key enzymes - B-HAD, and lipases
14
Comparing the Energy
Systems
• Table 2.6
• energy capacity - amount of ATP
able to be produced independent of
time
• power - rate of production - time factor
• *aerobic - table represents availability
from glycogen only - fat is unlimited
• Rest
– aerobic - supplies all ATP
• mainly fats and carbohydrates
– some lactate ~10 mg/dl in blood
• does not accumulate, but LDH active
15
Exercise
• Both anaerobic and aerobic
• relative contribution to ATP
production depends on
– intensity and/or duration
– state of training
– Dietary factors (replenishment of stores)
• Energy contribution vs time
• (*Assumes all out activity for time frame )
– Mcardle, Katch and Katch - Exercise
Physiology
– Immediate - phosphagens - major
contributor for up to 10 sec
– Anaerobic Glycolysis - majro
contributor for 30sec - 2.5 min
– Aerobic metabolism major contributor
for 3 min onward
• Contribution of energy systems is a
continuum, not an on or off situation
16
Experimental evidence
• Two types of exercise compared in
most of the following experiments
– near maximal - short duration
– sub maximal - longer duration
• Fig 2.18 glycogen depletion
– activities below 60 % (VO2 max) and
above 90% - limited glycogen depletion
– At 75% significant depletion - leading
to exhaustion (fatigue)
• 2.18b
– rate of depletion dependant on demand
– Volume of depletion related to duration
17
Short duration
• 2-3 minutes high intensity exercise
• fig 2.19 - major energy source CH2O
– ATP and PC will drop rapidly
– restored in recovery (rapidly)
• Aerobic contribution limited by its
low power output
– also takes 2-3 min to increase output
• oxygen deficit - period during which
level of O2 consumption is below that
necessary to supply all ATP required by
exercise demands
• ATP supplied by anaerobic systems
to make up for aerobic shortfall
– rapid accumulation of lactate
– 200 mg/dl in blood / muscle
18
Prolonged Exercise
• 10 minutes or longer
• Aerobic fat and carbohydrate
metabolism are main sources of ATP
• CHO dominate up to ~ 20 min
– fats minor but supportive role
• after ~1 hr fats become dominant
source of ATP
• at lower intensities (< 60% Hr max) fats
also have greater contribution
• fig. 2.20
– fatigue not associated with lactate, other
factors - discussed later in semester
• Fig 2-22 activities require blend of
anaerobic and aerobic systems
– energy continuum
19
Control and Regulation
• Matching provision of ATP to demand is
needed so performer does not experience
early or undue fatigue
• Enzymes, hormones, substrates interact to
modify flow through metabolic pathways
of each system
• Table 2.7
• Flow through different pathways is
often modified by activating and
inactivating key enzymes
• Influences over enzymes include;
–
–
–
–
–
–
high vs low energy state of cell(NAD+)
Hormone levels (epinephrine, glucagon)
“amplification” of hormone effects
competition for ADP (between enzymes)
adequacy of oxygen supply
power output requirements relative to
aerobic power (demand)
20
Regulation
• In general we observe;
– regulation within muscle cell,
– And influences from outside the cell
– both serving to modify regulatory
enzymes in each pathway
• Fig 2.23
• Energy State regulation
– ADP/ATP ratio
– very quick - tightly linked to rate of
energy expenditure
• Hormone Amplification
– cAMP 2nd messenger systems amplification
– Ep and Glucagon - activate
phosphorylase - glycogen breakdown
– lipase - fat breakdown
21
Regulation
• Substrates – eg. NADH - buildup
•
•
•
•
In cytosol stimulates LDH - frees NAD+
occurs when ETS is maximized
can not oxidize NADH fast enough
Also inhibitory in Krebs cycle (DH’s)
– eg. Inc Pyruvate
• stimulates PDH - entry into Krebs
• PDH also influenced by phophorylation
• Oxidative State Regulation
– O2 and ADP availability
– O2 stimulates cytochrome oxidase (CO)
• final step in ETC
– low O2 - inhibits Cytochrome Oxidase
– Leads to build up of NADH, FADH2
– key factor is oxygen availability vs
demand for ATP utilization
22
Recovery from Exercise
• Ch. 3
• process of recovery from exercise
involves transition from catabolic to
anabolic state
– breakdown of glycogen and fats to
replenishment of stores
– breakdown of protein to protein
synthesis for muscle growth and repair
• Our discussion of recovery will
include;
–
–
–
–
–
–
oxygen consumption post exercise
Replenishment of energy stores
Lactate metabolism(energy or glycogen)
Replenishment of oxygen stores
intensity and activity specific recovery
guidelines for recovery
23
Recovery Oxygen
• Recovery O2 - Net amount of
oxygen consumed during recovery
from exercise
– excess above rest in Litres of O2
• Fast and Slow components
– Based on slope of O2 curve
– first 2-3 min of recovery - O2
consumption declines fast
– then declines slowly to resting
• Fig 3.1
• Fast Component - first 2-3 minutes
–
–
–
–
restore myoglobin and blood oxygen
energy cost of elevated ventilation
energy cost of elevate heart activity
replenishment of phosphagen
• volume of O2 for fast component = area
under curve
– related to intensity not duration
24
Recovery Oxygen
• Slow Component
– elevated body temperature
• Q10 effect - inc metabolic activity
–
–
–
–
cost of ventilation and heart activity
ion redistribution Na+/K+ pump
glycogen re-synthesis
effect of catecholamines and thyroid
hormone
– oxidation of lactate serves as fuel for
many of these processes
• duration and intensity do not modify
slow component until threshold of
combined duration and intensity
– After 20 min and 80%
– We observe a 5 fold increase in the
volume of the slow component
25
Energy Stores
• Both phosphagens (ATP, CP) and
glycogen are depleted with exercise
• ATP/CP - recover in fast component
– measured by sterile biopsy, MRS
– rate of PC recovery indicative of net
oxidative ATP synthesis (VO2)
– study of ATP production
• 20-25 mmol/L/min glycogen and all fuels
• during exercise
– CP can drop to 20%, ATP to 70 %
– CP lowest at fatigue, rises immediately
with recovery
• Fig 3.2 - very rapid recovery of CP
– 30 sec 70%, 3-5 min 100% recovery
26
Phosphagen Recovery(cont.)
• Fig 3.3
– occlusion of blood flow - no
phosphogen recovery
– ** requires aerobic metabolism
– estimate 1.5 L of oxygen for ATP-PC
recovery
• Energetics of Recovery
• Fig 3.4
– breakdown carbs, fats some lactate
– produce ATP which reforms CP
– high degree of correlation between
phosphagen depletion and volume of
fast component oxygen
• Fig. 3.5
– anaerobic power in athlete related to
phosphagen potential - Wingate test
27