Muscle biochemistry

Assistant Professor of Medical

Biochemistry

Myofibril

Muscle Proteins

Myosin-thick filament structure

Role of ATP in contraction & relaxation

Role of Ca2+ and regulatory proteins

in contraction and relaxation

Role of Ca2+ and regulatory proteins

in contraction and relaxation

• Running required more energy than walking. (Med Sci Sports Exerc. 2004 Dec;36(12):2128-34.)

• ATP is important to performs muscle

contraction and relaxation.

• The ATP that exists at the start of

• contractile only support a few twitches.

• There is a need for continual production

of ATP by a muscle fiber

The three ways of production of ATP by a

muscle fiber

1. Some ATP is stored in a resting muscle. As

contraction starts, it is used up in seconds. More

ATP is generated from creatine phosphate for

about 15 seconds.

2. Each glucose molecule produces two ATP and

two molecules of pyruvic acid, which can be

converted to lactic acid If oxygen is not available,

which may contribute to muscle fatigue. This

occurs during strenuous exercise (oxygen cannot

be sufficiently delivered).

Glucose –lactate cycle (Cori cycle)

ADP represents the ‘last gasp’ of the

short-term energy stores:

3. Aerobic respiration is the breakdown of glucose or

fatty acids in the presence of oxygen (O2) to produce

carbon dioxide, water, and ATP. Approximately 95

percent of the ATP required for resting or

moderately active muscles is provided by aerobic

respiration, which takes place in mitochondria.

Substrate level phosphorylation and

oxidative phosporylation

Tissue Fuel utilized Fuel stored Fuel produced

for export

Resting

muscles

Fatty acids Glycogen None

Exercising

muscles

Glucose None Lactate and

alanine

Muscle tissues

fuel utilization stores and production

Types of skeletal muscle fiber

1. Slow-oxidative fibers (type I)

combine low myosin-ATPase activity

with high oxidative capacity.

2. Fast-oxidative fibers (type IIa)

combine high myosin-ATPase activity

with high oxidative capacity.

3. Fast-glycolytic fibers (type IIb)

combine high myosin-ATPase activity

with high glycolytic capacity.

Metabolic control during exercise

presents an excellent model for

explaining how body efficiently

responds to changes in

physiological processes.

Two different pattern of exercise:

1. The short duration, vigorous

exercise competitions (sprinting),

2. And the low power-output, long

distance running (marathon).

Sprinters muscle fiber

Sprinters possess a large muscle mass

mainly consisting of white muscle fibers

(Type IIb) that have high anaerobic

capacity, and store considerable larger

amount of glycogen, and creatine

phosphate.

marathon runners muscle fiber

While muscles in the marathon runners

are consisting mainly of the highly aerobic

red mucles, densly packed with

mitochondria and myoglobin. (Type I).

During the first seconds of a 100

meter sprint, the stimulation of the

myofibrillar ATPase by Ca 2+

decreasing the ATP level and

increasing ADP.

Metabolism in sprinters muscle fiber

ATP will rapidly be reformed at

expense of phosphocreatine

catalyzed by creatine kinase,

muscle content of phosphocreatine

may only last for few seconds

(15s).

Metabolism in sprinters muscle fiber

Metabolism in sprinters muscle fiber

Then the muscle turn to the stored

glycogen which will be anaerobically

degraded at a very rapid rate controlled by

the activity of myo-phosphorylase (enzyme

breaking glycogen→glucose).

Myophosphorylase is activated by

epinephrine and by high Ca levels.

In marathon running, (42,2 km),

ATP synthesis is mainly powered

by aerobic oxidation involving an

increased rate of fatty acid

mobilization and acetyl-CoA

oxidation, still a large proportion of

glucose will also be used

particularly in the first stage of the

exercise.

Metabolism in marathon runners

muscle fiber

Sustained exercise modulate the body

metabolism in a way that reduce the

muscle dependence on glucose and

gradually increases utilization of FA.

Metabolism in marathon runners

muscle fiber

Acetyl-CoA when increased as a result of

FA oxidation, it inhibits carbohydrate

(glucose) utilization.

Thereby prevent a severe hypoglycemia

that would occur if glucose utilization

went unchecked in marathon running.

Metabolism in marathon runners

muscle fiber

Atrophy

Nonfunctioning neuromuscular junctions,

lack of exercise and disuse lead to

atrophy of the muscle.

On the other hand exercise can produce

an increase in the size (hypertrophy) of

muscle fibers as well as changes in their

capacity for ATP production.

Hypertrophy

On the other hand exercise can produce

an increase in the size (hypertrophy) of

muscle fibers as well as changes in their

capacity for ATP production.

Effect of exercise

Low intensity but of long duration (aerobic

exercise), such as running and swimming,

produces increases in the number of

mitochondria in the muscle fibers. In

addition, there is an increase in the number

of capillaries around these fibers. These

changes lead to an increase in the capacity

for endurance activity with a minimum of

fatigue.

Effect of exercise

In contrast, short-duration, high-intensity

exercise (strength training), such as weight

lifting, affects primarily the fast- glycolytic

fibers (hypertrophy). In addition, the

glycolytic activity is increased . The result of

such exercise is an increase in the strength

of the muscle. Such muscles, although very

powerful, have little capacity for endurance,

and they fatigue rapidly.

LECTURE RESOURCES:

1. Harpers illustrated biochemistry. Robert K Murry,

Daryl K. Granner, Peter A Mayes, and Victor W.

Rodwell , 27th edition. ISBN: 978-0071461979.

Chapter 49.

2. Biochemistry . Stryer, L.; Berg, J. M.; Tymoczko,

J. L. (2002), New York: W. H. Freeman, 5th

ed. ISBN 0716746840. chapter 30 page=270-271

3. Vander, Sherman, Luciano's .Human Physiology:

The Mechanisms of Body Function. Information

center- chapter 9. the Muscle.

4. http://www.bmb.leeds.ac.uk/illingworth/muscle/