Anaerobic Metabolism During
High Intensity Exercise
Various Roles for Anaerobic
Metabolism
Essential when the demand for ATP is
greater than can be provided by aerobic
metabolism
At the onset of high-intensity exercise
At maximal O2 consumption
The onset of High Intensity
Exercise
Anaerobically derived ATP may contribute
80-90 % of the total
– O2 is in short supply until cardiovascular
system can meet demands
Near Maximal O2 Uptake
Near maximal O2 uptake, increases in
workload elicit greater contribution from
anaerobic sources
– Since aerobic metabolism is maximal, the only
other source of ATP is from non-oxidative
sources
Anaerobic Contribution
Decreases as Exercise
Progresses
30 s
– 80 % anaerobic/20 % aerobic
60-90 s
– 45 % anaerobic/55 % aerobic
120-180 s
– 30 % anaerobic/70 % aerobic
Insert fig 1.2
Insert Fig 1.1
Sources of Anaerobic ATP
CP or PCr degradation
Endogenous ATP
Glycolysis
PCr Degradation
Creatine PhosphoKinase
PCr + ADP + H+  ATP + Cr
Glycolysis
 Glycogen + 3 ADP + H+3 ATP + 2 lactate + 2 H+
– Can use this relationship to determine ATP provision from
glycolysis during intense exercise
– Take a post exercise muscle biopsy and multiply [La+] by 1.5
 Must also take into account lactate that leaves muscle
Adenosine Phosphorylation
Adenylate Kinase
2 ADP  ATP + AMP
• creates an ATP, but also leaves an AMP
Deamination
AMP + H+  IMP + NH4+
AMP Deaminase
• Conversion of AMP to IMP is irreversible
• Prevents buildup of AMP
• in conjunction with Adenylate Kinase prevents
accumulation of ADP
[ATP]/[ADP] Ratio
Important because it determines free energy
Hi [ATP]/[ADP] allows ATP to be
converted to ADP more easily
– If this happens, there is more free energy
Lo [ATP]/[ADP]
– ATPADP more difficult
– Less free energy
How do you keep the ratio
high?
Keep making ATP from ADP
Also, Adenylate Kinase
– ADP + ADP  ATP + AMP
– But AMP can go back to ADP
So
Deamination converts ADP to IMP and
removes loitering ADPs
Adenylate Kinase and AMP deaminase
work together to prevent AMP and ADP
buildup
Why do we want to keep ratio
high?
To maintain control of energy flow
We must generate ATP, but if ADP or AMP
accumulate we lose control of metabolism
Timing of Anaerobic Pathways
Traditional “Serial Metabolism”
PCr degradation immediate and only source
of ATP supply in first 10 s
When PCr depleted glycolysis begins
No overlap of two pathways
Recent evidence argues against this
PCr Degradation
PCr degradation is indeed instantaneous
Biopsies after 1.28 s of electrical
stimulation show PCr breakdown
Glycolysis Also Instantaneous
Elevated [La+] reported after 10 s cycling
110 % VO2max
Although no resting sample taken (Saltin et al.,
Jacobs et al.)
Other studies have shown [La+] after only 6
s, and PCr stores were not depleted after 6
or 10 s
Rates of Anaerobic
Metabolism
Anaerobic ATP must be provided at very
high rate
Power outputs of 2-4 times VO2max can be
attained for short periods
Even though anaerobic pathways provide
less ATP per mole of substrate than
oxidative pathways
Insert Table 1.2
Rate Continued
0-10 s - ~6.0 – 9.0 mmol ATP/kg dm/s
– Combined for PCr and glycolysis
30 s – PCr ~ 1.6 and glycolysis ~4.4
mmol/kg dm/s
– Assuming 25 % releas of lactate, ~5.8 for
glycolysis
Insert fig 1.4
Take Home
Highest rates of ATP provision from PCr
and glycolysis 0-10 s
From 10 – 30 s PCr stores are depleted
– Glycolytic rate ~ 50 % of intitial 10 s
– Glycolytic rate of ATP provision during 30s
maximal exercise, 3-4 times > PCr
Direct Measurement of
Anaerobic ATP Provision
Insert Table 1.3
Problems Associated with Measuring
Anaerobic ATP Provision
Must take pre and post-exercise biopsies
Must account for lactate release from
muscle
– Arterial and venous blood sampling
– If not, exhaustive exercise or….
– Spriet et al. and closed circulation
Glycolysis
During intense exercise bouts ~3 min,
glycolysis provides ~ 80 % total anaerobic
ATP
Glycolysis is activated more quickly than
aerobic metabolism
– provides ATP at a higher rate
Can provide more ATP than PCr
degradation
Glucose from where?

Glucose can come from blood or glycogen
 During short-intense exercise, primarily
from glycogen
 Uptake of glucose cannot meet glycolytic
demand
GLUT proteins
Regulation

Accumulation of G-6-P inhibits glucose
phosphorlation

Primary points of regulation are PHOS and
PFK
Why does G-6-P inhibit glucose
phosphorylation?

Low level of glycolytic flux
– Glycolysis isn’t moving very fast
– Must not need G-6-P

That glucose can be stored as glycogen
instead of being utilized for glycolysis
PHOS regulation

PHOS = glycogen phosphorylase

The enzyme responsible for breakdown of
glycogen to glucose

Removes one glucose at a time by adding Pi
(phosphorylating)
Insert fig 12.2 from Houston
PHOS cont’d

Km of PHOS for glycogen very low (1-2
mM)
– Means that PHOS has high affinity for
glycogen

This means PHOS can function effectively
even at low glycogen concentrations
More PHOS

Previous exercise can affect glycogenolytic
rate relative to glycogen concentration

For example during afternoon practice
following morning practice..
– If glycogen stores are low, glycogenolysis will
be reduced
– Higher glycogen stores will result in higher
relative glycogenolysis
Insert fig 1.5
Pi and PHOS regulation

Phosphorylation of PHOS (pretty redundant
eh?) results in conversion of forms
– b is inactive form
– a is active form
– Phosphorylation converts b form to a

Implications for activity???

At rest 10-20% of PHOS in a form

Conversion from b to a doesn’t necessarily
mean increased glycogenolysis

Free Pi also needs to be available for
elevated glycogenolysis to occur
Calcium activates PHOS
kinase

Phosphorylation of PHOS (again) results
from PHOS kinase

PHOS kinase activated by elevations in
intracellular [Ca2+]
Why would you want to tie PHOS to
intracellular [Ca 2+]??

With E/C coupling Ca2+ released from
sarcoplasmic reticulum

Intracellular [Ca2+] elevated drastically and
rapidly

Therefore glycogenolysis is tied closely to
muscular contraction
Acidosis hinders PHOS acitivity

Conversion of PHOS b to a is depressed under
acidic conditions

After repeated bouts of interval cycling, decreased
activation of glycogenolysis related to increasing
muscle acidity (Spriet et al.)

Although activity was still reduced in a second bout
1 hour after the first, where H+ had recovered
Phosphofructokinase (PFK)
regulation

Most important regulator of PFK activity is
ATP

ATP can bind to PFK at two sites and alter
its activity

Binds to catalytic site with high affinity

Can also bind to allosteric site
PFK cont’d

Binding to the allosteric site inhibits activity

So,… when [ATP] in the cell is high, PFK
will be inhibited
– no need for glycolysis, plenty of ATP

H+ can enhance ATP affinity for allosteric
site
– Provides feedback inhibition
Some other proposed
modulators

Inhibitors
– Citrate
– Phosphoglycerate
– Phophoenolpyruvate
– Mg2+

Promoters
– AMP and ADP
– Pi
– NH4+
– Fructose –2,6 diphosphate
Citrate

Probably not a major factor during short,
intense exercise

Aerobic metabolism does not contribute
greatly until later (>30 s)

Citrate probably does not accumulate within
the 30-60 s time frame
Promoters

ADP and AMP will accumulate rapidly at
the onset of anaerobic exercise
– Breakdown of PCr

H+ may be reduced at the onset of exercise
– Removing the ATP induced inhibition
Conclusion

PFK regulation is obviously a complicated matter

During exercise many of the promoters
(ADP,AMP, Pi, and NH4+) will accumulate

ATP will be reduced, but H+ should also rise

There may be unidentified factros which help
maintain the awkward balance of promotion and
inhibition during intense exercise