Endurance Adaptations

1
Endurance Adaptations
2
OxPhos during steady state exercise
During exercise OxPhos produces substrate for
crossbridge cycling
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
3
OxPhos during steady state exercise
During exercise OxPhos produces substrate for
crossbridge cycling, andcorssbridge cycling
produces substrate for OxPhos
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
4
OxPhos during steady state exercise
During steady state exercise at, say, 100W the
rate OxPhos is such that its rate of ATP
production by OxPhos
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
5
OxPhos during steady state exercise
During steady state exercise at, say, 100W the
rate OxPhos is such that its rate of ATP
production by OxPhos exactly matches the rate of
ATP consumption by XB cycling
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
6
OxPhos during steady state exercise
During steady state exercise at, say, 100W the
rate OxPhos is such that its rate of ATP
production by OxPhos exactly matches the rate of
ATP consumption by XB cycling, so the ATP
remains constant (i.e steady) as does the VO2
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
7
OxPhos during steady state exercise
Similarly during steady state exercise at, say,
100W the rate OxPhos is such that its rate of ADP
production by XB cycling
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
8
OxPhos during steady state exercise
Similarly during steady state exercise at, say,
100W the rate OxPhos is such that its rate of ADP
production by XB cycling exactly matches the rate
of ADP consumption by OxPhos cycling
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
9
OxPhos during steady state exercise
Similarly during steady state exercise at, say,
100W the rate OxPhos is such that its rate of ADP
production by XB cycling exactly matches the rate
of ADP consumption by OxPhos cycling, so the
ADP remains constant
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
10
OxPhos during steady state exercise
During steady state exercise at, say, 100W the
rate OxPhos is such that its rate of ATP
production
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
11
OxPhos during steady state exercise
The steady-state rate of OxPhos steady state
rates are determined by the- frequency of
substrate enzyme collisions which is
proportional to- ADP x enzymes
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
12
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W)
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
13
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W) At 100 W, rate of
XB cycling same between T UT

myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
14
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W) At 100 W, rate of
XB cycling same between T UT
So rate of ATP consumption same between T TU
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
15
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W) At 100 W, rate of
XB cycling same between T UT
So rate of ATP consumption rate of ADP
production same between T UT
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
16
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W) At 100 W, rate of
OxPhos same between T and UT
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
17
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W) At 100 W, rate of
OxPhos same between T and UT i.e. same VO2, same
rate ATP production
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
18
OxPhos during steady state exercise
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W) At 100 W, rate of
OxPhos same between T and UT i.e. same VO2, same
rate ATP production, same rate of ADP consumption
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
19
OxPhos during steady state exercise
However to produce that same- frequency of
substrate enzyme collisions
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
20
OxPhos during steady state exercise
However to produce that same- frequency of
substrate enzyme collisions T frequency
proportional to ½ ADP x 2enzyme
compared to . TT frequency proportional to
ADP x enzyme
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
21
OxPhos during steady state exercise
However to produce that same- frequency of
substrate enzyme collisions T frequency
proportional to ½ ADP x 2enzyme
compared to . TT frequency proportional to
ADP x enzyme
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
myosin ATPase
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2
??????????????? ATP ?NAD ?H2O
22
ADP driven reactions
ATPases
ADP Pi ? ATP
oxidative phosphorylation
ADP Pi ?(NADH H) ?O2 ? ATP ?NAD
?H2O
creatine kinase reaction
ADP CrP ? ATP Cr ...........................
....................... leads to Pi accumulation
adenalyte kinase reaction
ADP ADP ? ATP AMP ............................
.............. leads to AMP accumulation
glycolysis
ADP Pi ½ glucose ? ATP ½ lactate ½ H
........ leads to H accumulation
23
ADP driven reactions
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W)
½ ADP
oxidative phosphorylation (2x enzyme) . same
rate of reaction
ADP Pi ?(NADH H) ?O2 ? ATP ?NAD
?H2O
creatine kinase reaction
ADP CrP ? ATP Cr
adenalyte kinase reaction
ADP ADP ? ATP AMP
glycolysis
ADP Pi ½ glucose ? ATP ½ lactate ½ H
24
ADP driven reactions
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W)
½ ADP
oxidative phosphorylation (2x enzyme) . same
rate of reaction
ADP Pi ?(NADH H) ?O2 ? ATP ?NAD
?H2O
creatine kinase reaction ?
(forward) rate of reaction?
ADP CrP ? ATP Cr
adenalyte kinase reaction ? (forward)
rate of reaction ?
ADP ADP ? ATP AMP
glycolysis .. ? rate of
reaction ?
ADP Pi ½ glucose ? ATP ½ lactate ½ H
25
ADP driven reactions
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W)
½ ADP
oxidative phosphorylation (2x enzyme) . same
rate of reaction
ADP Pi ?(NADH H) ?O2 ? ATP ?NAD
?H2O
creatine kinase reaction ?
(forward) rate of reaction
ADP CrP ? ATP Cr
adenalyte kinase reaction ? (forward)
rate of reaction
ADP ADP ? ATP AMP
glycolysis .. ? rate of
reaction
ADP Pi ½ glucose ? ATP ½ lactate ½ H
26
ADP driven reactions
Lets compare trained (T) untrained (UT) at the
same sub-max power (say 100 W)
½ ADP
oxidative phosphorylation (2x enzyme) . same
rate of reaction
ADP Pi ?(NADH H) ?O2 ? ATP ?NAD
?H2O
creatine kinase reaction ?
(forward) rate of reaction
ADP CrP ? ATP Cr .............................
..................... ? Pi accumulation
adenalyte kinase reaction ? (forward)
rate of reaction
ADP ADP ? ATP AMP ............................
................. ? AMP accumulation
glycolysis .. ? rate of
reaction
ADP Pi ½ glucose ? ATP ½ lactate ½ H
........ ? H accumulation
27
Specificity?
28
endurance training Intensity lt 85
VO2max Duration gt 20 min
sprint training Intensity peak power Duration
30 s x repeats
high-resistance training Intensity 80 1
RM Duration 2 s x repeats
training mode
1? muscle structureadaptation

• mitochondrial volume density
• no change myofibril volume

?

• myofibril volume no change mitochondrial volume
  density

• endurance
• ? glycogen storage
• glcn use at same power
• etc. etc

sprint training ?peak power

• max force
• peak power

1? functionaladaptation
29
High Resistance Training Adaptations Healthy

• Green H et al. Am. J. Physiol. 276 R591R596,
  1998
• n 8 healthy sedentary young adults (avg age
  19 years old)
• Training program
• 12 weeks duration, training 3 times/week
• 3 exercises (parallel squats, incline leg
  presses, and leg extensions)
• each training session 3 sets of each exercise
  with each set performed for 6 8 repetitions
  maximum (RM.

30

• RESULTS
• 17 increase in mean muscle fibre cross
  sectional area
• no change in oxidative capacity (see below)

31
Sprint Training Adaptations Healthy

• Burgomaster KA et al. J Appl Physiol
  981985-1990, 2005
• n 16 healthy young adults (avg age 24
  years old)
• all subjects recreationally active ,
  participated in some form of exercise 2-3
  time/week (e.g. jogging, cycling, aerobics) but
  none were engaged in regular structured training
• 8 assigned to training group 8 assigned to
  control group
• Training program
• training consisted of 6 sessions of sprint
  interval training spread over 14 days (i.e. 3 x
  per week)
• each session consisted of 30s all-out efforts
  on an cycle ergometer subjects were verbally
  encouraged to pedal as fast as possible
  throughout the 30s
• between four-seven 30 s exercise bouts performed
  per session, with 4 min rest between bouts
• total exercise duration over 2 weeks 16 min

32

• RESULTS
• VO2peak no change
• Cycle endurance time to fatigue at 80 VO2max
• All performance trails conducted in the absence
  of verbal or time feedback

33

• RESULTS
• Biopsy for vastus lateralis before training
  program and 3 days after the final training
  session
• Subjects instructed to diet similar during pre
  and post training session and 24 prior to
  biopsies. No difference pre post as determined
  by food records.

38
26
34

• Burgomaster KA et al. J Appl Physiol 100
  20412047, 2006.
• n 16 healthy young adults (avg age 23
  years old)
• all subjects recreationally active ,
  participated in some form of exercise 2-3
  time/week (e.g. jogging, cycling, aerobics) but
  none were engaged in regular structured training
• 8 assigned to training group 8 assigned to
  control group
• Training program identical to 2005 study

35

• RESULTS
• Cycle time trial time required to perform 250
  kJ
• pre post change
• sprint interval training 9.6 reduction in
  time control . no change
• citrate synthase activity sprint
  interval training 11
• ? glycogen storage per exercise
• ? glycogenolysis during matched work
• unchanged RER during matched work
• VO2peak no change

36
Regulation of CHO use
37
Control of CHO mobilization use
glucose
Glut 4
glucose
phosphorylase
glycogen
glucose-1P
glucose-6P
fructose-6P
PFK
fructose-1,6P
pyruvate (x2)
38
Control of CHO use
Allosteric regulation of PFK activity by AMP
ATP - inhibits PFK
catalytic site
allosteric binding site (regulatory site)
AMP activates PFK
fructose-6P
substrates
ATP
39
Control of CHO use
Allosteric regulation of PFK activity by AMP
20 mM AMP
1 mM AMP
40
What stimulates glucose uptake during
exercise? one hypothesis
41
(No Transcript)
42
Exercise ? ? AMP ? activation of AMK kinase
43
Exercise ? ? AMP ? activation of AMK kinase
44
Exercise ? ? AMP ? activation of AMK kinase
45
Exercise ? ? AMP ? activation of AMK kinase ?
mobilization of GLUT4 transporters ? ? glucose
uptake
46

• Exercise
• (i) via AMPK (AMP activated protein kinase)
• AMPK activity increases with exercise,
  proportional to ex. Intensity
• AMPK can also be activated via the drug AICAR
  which also increases glucose transport

AICAR
?AMP
allosteric activation other mechanisms
47

• Exercise -TRAINING
• Activation of AMPK also stimulates increases in
• mitochondrial proteins
• GLUT4
• hexokinase

AICAR
?mito enzymes
?AMP
?hexokinase
allosteric activation other mechanisms
48
Regulation of mitochondrial content
49
How does activation of AMPK stimulate
mitochondrial biogenesis? (suggested reference
Reznick RM Shulman GI The role of AMP-activated
protein kinase in mitochondrial biogenesis J
Physiol 574 3339, 2006)
endurance exercise
? AMP
? AMPK activity
?
? PGC-1a
? nuclear transcription factors
? rate of transcription of genes for
mitochondrial proteins
nucleus
? mitochondrial proteins
AMPK AMP-activated protein kinase PGC-1a
peroxisome proliferator-activated receptor-?
coactivator-1a
50
actin gene
citrate synthase gene
DNA
transcription
transcription
actin mRNA
citrate synthase mRNA
translation
translation
actin
citrate synthase
51
actin gene
citrate synthase gene
DNA
transcription
? rate of transcription
actin mRNA
citrate synthase mRNA
translation
translation
actin
citrate synthase
endurance training
52
actin gene
citrate synthase gene
DNA
transcription
? rate of transcription
actin mRNA
? citrate synthase mRNA content
translation
translation
actin
citrate synthase
endurance training This leads to an increased
citrate synthase mRNA content in the cell
53
actin gene
citrate synthase gene
DNA
transcription
? rate of transcription
actin mRNA
? citrate synthase mRNA content
translation
? rate of translation
actin
citrate synthase
endurance training Since reach mRNA molecule can
be translated independently, the increase it
total mRNA allows an increase in the total rate
of translation
54
actin gene
citrate synthase gene
DNA
transcription
? rate of transcription
actin mRNA
? citrate synthase mRNA content
translation
? rate of translation
actin
? citrate synthase content
endurance training This increased rate in
translation results in the accumulation of
citrate synthase in the trained muscle cell