Muscle Metabolism

MUSCLE METABOLISM
(BIOCHEMISTRY OF PHYSICAL
ACTIVITY)
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TOPICS FOR DISCUSSION
1. MUSCLES- GENERAL ASPECTS AND MUSCLE TYPES
2. FUNCTIONS OF SKELETAL MUSCLE
3. GENERAL BIOCHEMICAL COMPOSITION OF SKELETAL
MUSCLE
4. HIGH ENERGY MOLECULES INVOLVED IN MUSCLE
CONTRACTION
5. ENERGY SOURCES FOR MUSCLE CONTRACTION
UNDER NORMAL CONDITION.
6. ENERGY SOURCES FOR MUSCLE CONTRACTION
DURING STARVATION/ FASTING.
7. CLINICAL ASPECTS OF MUSCLE METABOLISM
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MUSCLE /DIFFERENT TYPES
Muscles are the contractile tissues of the body.
There are three types of muscle tissues in the body.
1.Skeletal Muscle or striated or voluntary muscle
-present attached to the bone/skeleton and brings about
the movements of body parts.
2.Smooth Muscle or non striated or involuntary muscle
- Present in tubular internal organs such as digestive tract,
trachea, blood vessels, uterus etc.
3.Cardiac Muscle
-present in heart wall and also called myocardium.
All types of muscle tissues are characterized by their
contractility and elasticity.
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CARDIAC MUSCLE
Branching cells
One/two nuclei per cell
Striated
Involuntary
Medium speed of contraction
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SMOOTH MUSCLES
Fusiform cells
One nucleus per cell
Non-striated
Involuntary
Slow, wave-like contractions
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SKELETAL MUSCLE
Long cylindrical cells
Many nuclei per cell
Striated
Voluntary
Rapid contractions
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FUNCTIONS OF SKELETAL MUSCLE
Produce movement
Maintain posture & body position
Support Soft Tissues
Maintain body temperature
Store nutrient reserves
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BIOCHEMICAL COMPOSITION OF
SKELETAL MUSCLE
Approximate Biochemical composition of
the muscle tissue
Water- 75%
Proteins 20 %
Other organic and inorganic materials 5 %
The major proteins present in muscle tissue are myosin ,
actin.
Apart from these there are also other proteins like troponin
and tropomyosin which are also important in muscle
contraction.
It also includes various enzymes and various transport
proteins involved in muscle cell metabolism.
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BIOCHEMICAL COMPOSITION OF
SKELETAL MUSCLE
The major carbohydrate present in skeletal muscle tissue
is glycogen. It is an energy reserve /source.
- Other organic compounds mainly include creatine P (
also called phospho creatine) and ATP.
- Creatine - P is a high energy molecule specifically
involved in muscle contraction.
- ATP is the immediate source of energy for muscle
contraction where as creatine P is the reserve form.
- Resting skeletal muscle contains 4-6 times creatine P
than ATP.
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HIGH ENERGY MOLECULES IN MUSCLE
CONTRACTION
ATP is the immediate source of energy for muscle
contraction, but its amount in the muscle is very small
and is just enough for a fraction of a second.
In human beings, ATP required for muscle
contraction is formed with the help of an
accessory high energy molecule called creatine
P.
Creatine P react with ADP to form ATP and creatine.
This reaction is catalyzed by an enzyme called creatine
kinase ( CK) also called creatine phospho kinase (
CPK).
This reaction is called Lohmann reaction.
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HIGH ENERGYMOLECULES IN MUSCLE
CONTRACTION
This reaction is reversible and creatine P can
be synthesized back from creatine and ATP
during the recovery period following a muscle
contraction, when ATP becomes available.
This reaction is catalyzed by another enzyme
called ATP creatine trans-phosphorylase.
ATP can also be formed by another
mechanism with the help of an enzyme
called myokinase.
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CONTRACTION
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CONTRACTION
ATP creatine transphosphorylase
ATP + CREATINE CREATINE PHOSPHATE
CPK
ADP+ CREATINE PHOSPHATE CREATINE + ATP
Myokinase
2 ADP 1 AMP + 1 ATP
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Turn over of creatine/creatine -P
The synthesis of creatine is taking place partially in the kidney and
partially in the liver.
Creatine is synthesized from two amino acids ,namely Arginine and
Glycine in a two step process.
The first /step reaction takes place in the kidney in which Arginine
and glycine combines to form guanido- acetic aid.
The second step takes place in the liver during which
guanidoacetate is methylated to form creatine.
Creatine is then transported to the muscle where it is
phosphorylated to creatine P ( the active form/phosphagen
form).
Very negligible amount of creatine P is dephosphorylated
spontaneously and cyclised (by non-enzymatic reaction) to form
creatinine ( a waste product) which is excreted in the urine.
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ENERGY SOURCE FOR SKELETAL
MUSCLE
Fatty acids, D- Glucose ,amino acids
and ketone bodies are the general
energy sources for muscle contraction.
The type of fuel molecule utilized vary depending
on the functional state of the muscle-such as
resting muscle , moderate muscular activity and
peak muscular activity.
And also depending on the metabolic conditions-
normal condition or starvation.
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MUSCLE
1.Resting muscle: Fatty acid are the energy
source for resting skeletal muscle.
-The ATP produced by fatty acid oxidation is
used for the formation of creatine-
phosphate and glycogen ( the energy
reserve).
-Glycogen is synthesized from D- Glucose by a
process known as glycogenesis or glycogen
synthesis
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MUSCLE
2. Moderate muscular activity: During moderate muscular exercise
both glucose and fatty acids are utilised as sources of energy.
a)Catabolism of D- Glucose: consists of three stages.
-Glucose is oxidised by glycolysis to form pyruvate.
-Pyruvate is converted to acetyl COA by Pyruvate dehydrogenase
complex ( PDC) enzyme).
-Acetyl COA is completely oxidised by the citric acid cycle in to
CO2 and water.
b)Catabolism of fatty acids: consists of two stages.
-Fatty acids are degraded in to acetyl COA by a process called beta
oxidation.
-Acetyl COA is further degraded in to CO2 and water in the citric
acid cycle
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MUSCLE
3. Peak muscular activity: Heavily exercising muscle
needs more energy.
There will be a high requirement of fuel molecules
such as fatty acids and D- Glucose as well as
molecular oxygen to the muscle tissue because of
the increasing energy demand.
By physiological adaptation ( high heart beat rate
/increased blood circulation and high ventilation
rate ), the body will try to manage this condition.
But still the supply will become insufficient.
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MUSCLE
In this condition the energy production will be diminished because of two
reasons. 1)shortage in the supply of fuel molecule 2) insufficiency of O2.
(there will be a block in aerobic mode of oxidation/mitochondria dependent
oxidation which is dependent on O2 ).
-The catabolism of fatty acids ( both beta oxidation and citric acid cycle)
take place only in the mitochondria.
-Since fatty acid oxidation is aerobic type( O2 dependent) ,the rate of fatty
acid oxidation is considerably diminished in the absence of oxygen.
The normal oxidation of D- Glucose also is aerobic type depending on
mitochondria. Due to the lack of oxygen and insufficient supply of D-
Glucose ,the energy production by normal aerobic way of glucose
oxidation also will be dimnished.
In this condition mitochondria contribute only 1/3

of the ATP requirement.
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MUSCLE
In short, aerobic mode of energy production from
D- Glucose and fatty acid depending on
mitochondria and O2 will be diminished to 30
%.
In contrast, the muscle need more amounts of ATP
at this time to support muscle contraction
process.
In order to face this difficult situation muscle
tissue will be forced to shift to anaerobic mode
of energy production with glycogen as the fuel
molecule.
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MUSCLE:ANAEROBIC GLYCOLYSIS
During heavy muscular exercise there is an
increased demand for ATP. Due to the
insufficient supply of O2 the aerobic mode of
energy production by mitochondria will be
diminished considerably (to one third of the
total).
In order to face this critical situation the muscle
tissue will be forced to use the stored glycogen
as an energy source by anaerobic mode of
oxidation which is independent of the
mitochondria ( takes place in the cytosol).
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ANAEROBIC GLYCOLYSIS
During heavy muscular work there will be the secretion
of adrenaline ( epinephrine ) by the adrenal medulla.
Adrenaline is having a stimulating effect on
glycogenolysis in muscle and liver.
Adrenaline will activate the chief enzyme involved in
glycogenolysis,called glycogen phosphorylase.
As a result of glycogenolysis glycogen will be degraded
in to Glucose 6- P .
Glucose 6- P will be further degraded in to 2 molecules
of pyruvate.
Pyruvate is then reduced to lactate in the cytosol itself.
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The conversion of Pyruvate in to lactate is called
anaerobic glycolysis.
It takes place in the cytosol of skeletal muscle cells
during heavy muscular exercise/in the absence of
sufficient oxygen (and also in RBC under normal
condition).
The reaction is catalyzed by an enzyme called Lactate
dehydrogenase (LDH) which requires NADH+H+ as a
co-enzyme.
The net energy production in anaerobic glycolysis is
only 2 molecules of ATP per molecule of Glucose.
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Reutilization of lactate:
As a result of severe muscular exercise too much amounts of Lactate
will be accumulated in the skeletal muscle.
This in turn lead to a decrease in muscular pH resulting in a painful
condition known as muscle cramp.
---This lactate is then gradually liberated in to the blood circulation.
----Via blood it reaches the liver. In the liver the lactate is effectively re-
utilized for the synthesis of D- Glucose by a process known as
gluconeogenesis.
The cyclic process of conversion of lactate to D-glucose(by
gluconeogenesis) then to glycogen(by glycogenesis in muscle)and
then to D- Glucose( by glycogenolysis in muscle)and again back to
lactate ( (by anaerobic glycolysis in muscle) is known as Coris
cycle( Cori- name of the scientist).
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CHANGES IN MUSCLE METABOLISM
DURING FASTING AND STARVATION
During normal metabolic conditions the chief
energy sources for skeletal muscles are Fatty
acids ( resting state ) ,Fatty acids and D-
Glucose ( moderate activity) and mainly
D- glucose/anaerobic glycolysis ( peak
activity/severe muscular exercise).
Fasting and starvation will lead to a change in
the metabolism of skeletal muscle .
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During the initial hours of fasting( 9-18 hours
of not consuming food )Glycogen store in the
skeletal muscle will be the source of energy
for muscle contraction.
By 18 hours of fasting the glycogen store of
the muscle tissue will be completely utilized.
Negligible amount of D- Glucose produced by
the liver as a result of gluconeogenesis will
not be sufficient for the muscular activities.
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During this situation there will be a change in
the overall metabolism of muscle tissue in
order to face the emergency situation.
The changes are:
1.The muscle tissue started utilizing ketone
bodies as a source of energy.
2. Amino acids becomes a source of energy for
muscle contraction.
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Ketone body as energy source for
skeletal muscle during starvation
The ketone bodies include 3 types of
molecules( acetone , aceto-acetate and beta-
hydroxybutyrate) which are produced from
acetyl COA by the liver by a process known as
ketogenesis.
Ketogenesis takes place in the liver at a very
low rate during normal condition .
But during starvation ketogenesis will be
activated.
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During starvation ,there will be an increased rate of lipid
mobilization( break down of neutral fat in the adipose
tissue)/beta oxidation of fatty acid in the liver resulting in the
accumulation of large quantities of acetyl COA in the liver.
All these acetyl COA cannot be further degraded by citric acid cycle
because ,,
oxalocaetate is a molecule required for the entry of acetyl
COA in to the citric acid cycle. During starvation major
portion of the oxaloacetate will be deviated for
glluconeogenesis in the liver(under the influence of
glucagon).
The decrease in the concentration of oxalo acetate will
limit/restrict the oxidation of acetyl COA and it will
accumulate in the mitochondria excessively.
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In order to bring down/decrease the
concentration of acetyl COA liver will convert
the excess acetyl COA in to ketone bodies(
acetone aceto-acetate and beta-hydroxy
butyrate)- called ketogenesis.
Ketone bodies will be liberated in to the
blood and circulated to different extra-
hepatic tissue.
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Ketone body as energy source for skeletal
muscle during starvation-ketogenesis
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Ketone body as energy source for skeletal muscle
during starvation-ketogenesis
Major Pathway
Aceto-acetyl COA + Acetyl COA
HMG COA synthase
Beta hydroxyl beta methyl; glutaryl COA +COASH
HMG COA lyase
Aceto acetate + Acetyl COA
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muscle during starvation-ketogenesis
NADH beta-hydroxy butyrate dehydrogenase
4. Aceto acetate Beta hydroxyl butyrate
NAD+
5. Acetoacetate
Spontaneous/ non enzymatic
CO2
Acetone (takes place in the circulation)
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muscle during starvation-ketolysis
Acetone will be excreted by evaporation from the body
surface and also through the exhaling air( feel acetone
smell).
Where as aceto-acetate and beta-hydroxy butyrate are
utilized(oxidised) by certain tissues such as brain ,
myocardium, skeletal muscle and kidney as an energy
source. This process of utilization of ketone bodies is called
ketolysis.
Ketolysis involves the enzymatic conversion of aceto
acetate and beta-hydroxybutyrate in to acetyl COA.
Acetyl COA is further degraded in to CO2 and H2 0 by the
citric acid cycle to liberate ATP. This ATP becomes the
source of energy for muscle contraction.
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The heart muscle and renal cortex prefers ketone
bodies over D- Glucose.
The brain and skeletal muscle use ketone bodies in the
absence of sufficient quantities of D- Glucose.
This means that the absence of sufficient quantities of D-
Glucose enforce the skeletal muscle to use ketone bodies
as an energy source during starvation.
In this way liver helps muscle and other tissue to
over come starvation by providing D- Glucose (by
glycogenolysis in liver) by providing ketone bodies
( ketogenesis in liver).
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Ketogenesis- synthesis of ketone bodies. Takes plce in liver.
Ketolysis- Lysis/ oxidation / utilization of ketone bodies .
Takes place in skeletal muscle , brain myocardium and kidney.
Ketonemia- excessive accumulation of ketone bodies in
blood. Occurs during severe starvation and diabetes mellitus.
Ketosis- the increase in the concentration of ketone bodies all
over the body tissues/accumulation of ketone bodies.
Keto-acidosis- the decrease in the pH of the blood during
ketosis.
Starvation induced ketosis & diabetes induced ketosis.
Ketoneuria- the presence of more concentration of ketone
bodies in urine. 51
Amino acid as an energy source for
Amino acids are generally the third source of energy in an individual
under normal metabolic conditions after carbohydrate and fatty
acids.
Even though there is fat storage ( TAG in adipose tissue)and
carbohydrate storage ( Glycogen in liver and skeletal muscle) as
energy reserve to survive in the emergency conditions ( like
starvation) ,
there is no amino acid store in our body.
How ever, during severe starvation when the glycogen and fat are
about to finish, the body protein( mainly muscle protein and
albumin of blood plasma )will be degraded and amino acids are
liberated(STARVATION INDUCED BODY PROTEIN DEGRADATION).
The liberated amino acids serve different
functions.
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Amino acid as an energy source for
1. Glucogenic amino acids( 16/21) become the precursor of
D- Glucose in the liver by gluconeogenesis.
-D- Glucose is the only source of energy for RBCs ( NS will
utilise ketone bodies during starvation, but RBCs not).
2. Ketogenic amino acids(3/21) become the precursor of

ketone bodies- the energy source for skeletal muscle ,
myocardium, kidney and brain during starvation.
3. Amino acids are de- aminated ( by different mechanisms)

and the carbon skeletons are oxidised by the citric acid
cycle to produce energy for muscle contraction.
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Clinical aspects of muscle metabolism
1.Muscle Fatigue
When muscles can no longer perform a required activity, it
is said to be fatigued.
Characteristics of Muscle Fatigue

Depletion of metabolic reserves
Damage to sarcolemma and sarcoplasmic reticulum
Low pH (lactic acid)
Muscle exhaustion and pain
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2. Muscle cramp- muscle pain experienced during /after
sever muscular exercise .
-This is because of the accumulation of lactic acid (
formed during anaerobic glycolysis)and a decrease in
muscle p H.
3. Duchnee muscular distrophy is a genetic disorder (
progressive type)characterised by muscle deterioration
and non functioning of the muscle. It is because of the
degeneration/atrophy / death of myocytes.
This usually happens to muscles of pelvic and shoulder
girdle.
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4. Malignant hyper thermia: a serious complication arise
during certain type of anaesthesia due to the accumulation
of Ca ++ ions in the cytosol of the skeletal myocytes-
causing rigor and generation of excessive heat.
5.Mc Ardles disease: is a muscular disorder characterised by
muscle weakness during exercise- known as exercise
intolerance.
This is because of the genetic deficiency of an enzyme called
muscle glycogen phosphorylase which is involved in
muscle glycogenolysis ( glycogen breakdown).
Anaerobic mode of energy production will be blocked in this
condition because of a block in muscle glycogenolysis.
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Muscle mass enlargement: muscle
hypertrophy
Muscle hypertrophy involves an increase in size
of skeletal muscle through a growth in size of its
component cells.
Two factors contribute to hypertrophy:
1)Sarcoplasmic hypertrophy, which focuses more on
increased muscle glycogen storage &
2)Myofibrillarhypertrophy, which focuses more on
increased myofibril size.
However, neither happens in isolation, which is why
top-level bodybuilders and strongman
competitors differ so greatly in muscle size and
strength.
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hypertrophy
In the bodybuilding and fitness community skeletal
muscle hypertrophy is described as being in one of two
types: Sarcoplasmic or myofibrillar.
During sarcoplasmic hypertrophy, the volume
of sarcoplasmic fluid in the muscle cell increases with
no accompanying increase in muscular strength.
During myofibrillar hypertrophy contractile

proteins(actin and myosin increase in number and
add to muscular strength as well as a small increase in
the size of the muscle.
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hypertrophy
Sarcoplasmic hypertrophy is greater in the
muscles of bodybuilders while myofibrillar
hypertrophy is more dominant in Olympic
weightlifters.
These two forms of adaptations rarely occur
completely independently of one another; one
can experience a large increase in fluid with a
slight increase in proteins, a large increase in
proteins with a small increase in fluid, or a
relatively balanced combination of the two.
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AT THE END ONE FUNNY QUESTION PLEASE,,,,,,,,,,,,,,
WHO IS HAVING MORE MUSCLE SIZE

AND STRENGTH??????MALES OR
FEMALES.
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Muscle Metabolism

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MUSCLE METABOLISM

In this condition mitochondria contribute only 1/3

Aceto-acetyl COA + Acetyl COA

HMG COA synthase

Beta hydroxyl beta methyl; glutaryl COA +COASH

HMG COA lyase

Aceto acetate + Acetyl COA

Spontaneous/ non enzymatic

Acetone (takes place in the circulation)

2. Ketogenic amino acids(3/21) become the precursor of

3. Amino acids are de- aminated ( by different mechanisms)

Characteristics of Muscle Fatigue

During myofibrillar hypertrophy contractile

WHO IS HAVING MORE MUSCLE SIZE

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