Aerobic and Anaerobic Metabolism

in Exercising Muscles

Musculoskeletal and Skin Module

Year-2; MBBS (UniKL) Programme
March 12, 2021

AP Dr. A. T. M. Emdadul Haque

UniKL-Royal College of Medicine Perak
Objectives:
 At the end of this lecture, you should be able to
explain the:
 types of energy sources that can be used by muscles;
 metabolic changes in aerobic and anaerobic exercises.

Lecture outline:
 Energy requirements during aerobic and anaerobic exercises
 Generation of ATP from different metabolic fuels during
aerobic and anaerobic exercises
 Adenylate kinase reaction and its role in the stimulation of
glycogenolysis and glycolysis
 Alanine cycle and Cori cycle, and their role in exercise
 Muscle fatigue: Why cardiac muscles are not affected.
 Muscles
 Three different types of muscles are found in vertebrate animals:
 Cardiac muscles
 Smooth muscles
 Skeletal muscles
 The primary function of the muscles is to convert the chemical
energy into mechanical work, through the breakdown of ATP →
muscle contraction.
 Concentric (Isotonic) contractions: Muscle actively shortens
 Contractions that permit the muscle to shorten. An example of a concentric
contraction is the raising of a weight during a bicep curl.
 Eccentric contractions: Muscle actively lengthens
 During normal activity, muscles are often active while they are lengthening.
Classic examples of this are walking.
 Isometric (same length) contraction: If a stimulated muscle does
not shorten or lengthen, but simply exerts tension.
 Passive Stretch: Muscle Passively Lengthens
 the muscle is lengthened while in a passive state.
 Types of muscle Fibres
 Two different types of voluntary muscle fibres:
 Slow twitch fibres: contract for long periods of time but with
little force
 Fast twitch fibres: contract quickly and powerfully but gets
fatigue very rapidly
 Type I or “slow-twitch" fibres
 loaded with mitochondria and
 depend on cellular respiration for ATP production
 resistant to fatigue
 rich in myoglobin and hence red in color
 dominant in muscles that depend on tonus, e.g., those responsible for
posture
 Type II or "fast-twitch" fibres
 few mitochondria
 rich in glycogen and
 depend on glycolysis for ATP production
 fatigue easily
 low in myoglobin hence whitish in color
 dominant in muscles used for rapid movement
 Fueling Muscle Contraction
During exercise, the primary nutrients used for energy are fats &
CHOs, with protein contributing a relatively small amount of total
energy used. ATP is the immediate source of energy for muscle
contraction.
Muscle cells can produce ATP by
any one or combination of 3
metabolic pathways:

• ATP-PC (phosphagen) system;

• Glycogen-lactate system; and
• Aerobic metabolism (oxidative
phosphorylation).

ATP-PC system and glycolysis are

two pathways, capable of
producing ATP without O2.
 ATP and Phosphocreatine
 Without energy from ATP, muscle contraction
will not occur.
 Myosin acts as an enzyme to break ATP into
ADP, and releases energy to cause
contraction.
 ATP and water are reacted to produce ADP,
Pi, a proton (H+) and the energy that drives
the desired process. The protons acidify the
cellular environment and contribute to
fatigue.

Phosphocreatine contains high energy

phosphate bonds, is 3-8 times as
abundant as ATP.
 Creatine phosphate
 The phosphorylated derivative of creatine found in
muscle, is a high-energy compound that can reversibly
donate a phosphate group to ADP to form ATP.

 After first few seconds of intense muscular contraction,

it provides a small but rapidly mobilized reserve of high-
energy phosphates to maintain intracellular ATP level.

 The amount of creatine phosphate in the body is

proportional to the muscle mass.
 Synthesis of Creatine
Glycine and guanidono group of arginine plus
a methyl group from S-adenosyl methionine.
Creatine is phosphorylated using ATP
reversibly by creatine kinase.

The presence of plasma CK is indicative of

tissue damage, and is used in the diagnosis of
Myocardial Infarction.

Creatine & creatine phosphate spontaneously

cyclize to form creatinine which is excreted in
urine.

Creatinine excretion is used to estimate

muscle mass. When muscle mass decreases
→ creatinine excretion falls.

Increased serum creatinine → kidney malfunction.

 Fuel utilization during exercise
 At rest, almost 100% of ATP are produced by aerobic
metabolism.

 The rate of ATP use in skeletal muscle during exercise can be as

much as 100 times than that in resting.

 ATP and creatine phosphate are rapidly used up if not

continuously regenerated.

 Anaerobic glycolysis is important as a source of ATP in 3

conditions:
 At the onset of exercise
 In fast-twitch glycolytic muscle fibers
 During strenuous activity
Estimation of
Fuel Utilisation
The respiratory
exchange ratio
(Respiratory Quotient)
is the ratio of CO2
produced to the O2
consumed.
To use RQ as an
estimate of substrate
utilization during
exercise, the subject
must be in a steady
state.
 Exercise intensity and
Fuel selection
As the exercise intensity
increases, there is progressive
increase in CHO metabolism &
a decrease in fat metabolism.

Exercise duration
and Fuel selection
During prolonged low-
intensity exercise (>30 min),
there is gradual shift from
CHO metabolism toward fat
metabolism.
 Effect of exercise
duration on muscle
fuel source

Influence of exercise
intensity on muscle
fuel source.
Aerobic Exercise: long distance/marathon running
1. Respiratory quotient or RER
decreases, indicating the
progressive switch from glycogen
to fatty acid oxidation. Lipolysis
gradually increases as glucose
stores are depleted.
2. Rate of fatty acid oxidation
increases due to decreased
[malonyl-CoA], thereby
increasing CPT-1 activity for fatty
acid transport.
3. Increased [cAMP] leads to
inactivation of acetyl CoA
carboxylase.
4. Unlike prolonged fasting, there is
little increase in [ketone bodies]
during exercise.
Anaerobic Exercise:- sprinting, weight lifting
1. Little inter-organ cooperation.
2. Blood vessels in muscle are
compressed during peak contraction,
isolating muscle cells from rest of the
body.
3. Muscle relies on stored glycogen and
creatine-phosphate for ATP synthesis.
4. Glycolysis becomes the primary source
for ATP generation.
Fuels used during exercise: The pattern of fuel
utilization changes with the duration of exercise.
The preferential use of fatty acids over glucose in skeletal muscles depends on
the following factors:
1. The availability of free fatty acids in blood during prolonged exercise;
2. Inhibition of glycolysis by product of fatty acid oxidation (PFK-1 activity is
decreased);

3. Reduced glucose
transport via GLUT-4
during long-term
exercise;
4. Increased ketone
bodies oxidation during
exercise; and
5. Inactivation of acetyl-
CoA carboxylase for
muscle to use fatty
acids.
 Oxygen uptake during exercise
In the transition from rest to light or moderate exercise, oxygen
uptake increases rapidly, and reaches a steady state within 1-4
minutes.
The delay in oxygen uptake at the beginning of exercise is termed
oxygen deficit.

Trained subjects
have a lower
oxygen deficit.
↓
Less production of
lactic acid
Exercise time/min
 Maximal oxygen uptake (VO2max)
 Oxygen uptake is linearly related to the workload. As the exercise
intensity increases, VO2 increases proportionally. However, there
comes a point at which the Vo2 ceases to rise even though the
exercise intensity continues to rise.
 Maximal oxygen uptake is considered to be the benchmark of
maximal aerobic power.
 The VO2max assesses the maximal ability of the body to deliver
and utilize oxygen and is related to the ability to perform
prolonged exercise.
 Factors Affecting VO2 max
 Age: Generally, VO2max is the highest at age 20 and decreases nearly 30%
by age 65.
 Gender: A woman's VO2max is in general about 20% lower than a man's
VO2 max.
 Altitude: An athlete will generally have 5% decrease in VO2max results
with a 5,000 feet gain in altitude.
• In the transition from rest to light/moderate exercise, oxygen uptake
increases rapidly, generally reaching a steady state within one to four
minutes.

• The failure of oxygen uptake to increase instantly at the beginning of

the exercise suggests that anaerobic pathways contribute to the
overall production on ATP. After a steady state is reached, the body’s
ATP requirement is met via aerobic metabolism.
 VO2 max - Men vs. Women
 Absolute values of VO2max are
typically 40-60% higher in men
than in women.
 The average young untrained Trained vs. untrained
male will have a VO2max of
approximately 3.5
litres/minute and 45
ml/kg/min.
 The average young untrained
female will score a VO2max of
approximately 2.0
litres/minute and 38
ml/kg/min.

Exercise time (min)

 Oxygen Uptake During Recovery
EPOC (Excess Post-exercise Oxygen Consumption) is the recovery period after
exercise where there is elevated oxygen consumption. It is the amount of oxygen
consumed during recovery in excess of that which would have ordinarily been
consumed at rest.

The excess O2 is
used to:

1) resynthesis of
phosphocreatine;
2) replenish muscle &
blood O2 stores;
3) conversion of lactic
acid into glucose;
4) conversion of AMP
& ADP to ATP;
 Adenylate Kinase Reaction (AK)
With increasing exercise intensity the AK reaction also increases
its activity. This reaction combines 2 ADP molecules to produce
an ATP molecule and an AMP molecule. The presence of AMP in
the cell helps stimulate increased rates of glycolysis.

AMP Deaminase Reaction

Some of the AMP produced by the AK reaction is converted into inosine
monophosphate (IMP) and NH4 with the addition of a proton. Because of
the consumption of a proton this reaction also provides some buffering to
acidosis.
 Muscle Fatigue
 Muscle fatigue is the transient decrease in performance
capacity of muscles, usually evidenced by a failure to
maintain or develop a certain expected force or power.
 Caused by:
 oxygen deficiency
 accumulation of metabolites such as CO2 and lactic acid
 Factors contributing:
 In high intensity exercise- accumulation of Pi & H+ in muscle
fiber.
 In prolonged exercise- decreased release of Ca++ from SR 
fewer myosin cross-bridges in strong binding state  reduced
muscle force production  failure of excitation-contraction
coupling.
 Directly associated with a mismatch between the rate at
which muscle uses ATP and the rate at which ATP is
supplied.
 Cardiac muscle does not fatigue. Why?
 Cardiac muscle is red-colored involuntary muscle that contracts
automatically and rhythmically.

 It is striated and multinucleated, like skeletal muscle. The muscle is

fast-acting and powerful. It is under the control of the autonomic
nervous system and continuously contracts and relaxes
throughout life.

 Cardiac muscle has a built-in mechanism to maintain the necessary

rhythmical contraction independently of any nervous connections.

 Cardiac muscle has the advantage of being supplied with oxygen

from the blood stream via the coronary artery. the blood supply to
cardiac muscle cells is very rich in oxygen, making unnecessary for
the heart to switch to anaerobic metabolism to produce ATP.

 In general, cardiac muscle cells have many more mitochondria

than skeletal muscle cells, and are able to produce more ATP,
when oxygen is in good supply.
 References/Recommended Reading
 Devlin, TM. Textbook of BIOCHEMISTRY with clinical correlations
(5th edition).
 Champe, Harvey, Ferrier. Lippincott’s Illustrated Reviews of
BIOCHEMISTRY (3rd edition).
 Smith, Marks, Lieberman. Basic Medical Biochemistry, A clinical
approach (2nd edition).
 Scott k. Powers, Edward T. Howly. Exercise physiology (3rd
edition).
 Guyton and Hall. Textbook of Medical Physiology.
 McArdle W. D, Katch F. I & Katch V. L. Exercise Physiology.
 Some Internet websites.
Activation of muscle glycogenolysis and glycolysis
by AMP (allosterically activated)
 The Cori and Alanine Cycles
 The Cori and alanine
cycles depend on
gluconeogenesis in liver
followed by delivery of
glucose and its use in
peripheral tissues.

 The cycles are only

functional between
liver & tissues that do
not completely oxidize
glucose to CO2 & H2O.

Peripheral tissues (exercising skeletal muscles and RBC) release

lactate in Cori cycle, and alanine in alanine cycle as the end product of
glucose metabolism.
Two mol of ATP per molecules of glucose are produced in Cori cycle.
 Alanine Cycle

NADH generated in
alanine cycle is not
used to reduce
pyruvate to lactate.

6-8 mol of ATP are

formed per glucose
molecule in
peripheral tissues
that participate in
alanine cycle.