Muscle Metabolism

Page 1.  Introduction

Skeletal muscle must continuously make ATP to provide the energy for muscle contraction.

Page 2.  Goals

To understand the cellular processes for synthesis of ATP.

To compare and contrast aerobic and anaerobic processes in the muscle cell.

To examine the differences in ATP synthesis among different types of muscle cells.

Page 3.  Role of ATP

Important roles of ATP in muscle contraction:

1. ATP binds to myosin heads and upon hydrolysis into ADP and Pi, transfers its energy to the cross bridge, energizing it.

2. ATP is responsible for disconnecting the myosin cross bridge at the conclusion of a power stroke.

3. ATP provides the energy for the calcium ion pump which actively transports calcium ions back into the sarcoplasmic reticulum.

Page 4.  Structure of Adenosine Triphosphate (ATP)

Structure of ATP:

Note: ATP has three phosphate groups.  The structure of a phosphate group (Pi) is:

The bond between the last two phosphate groups is high energy and therefore blinking yellow.

Page 5.  Hydrolysis of ATP

This animation shows the hydrolysis of ATP. 

Summary of the hydrolysis of ATP:

ATP   +   H2O        ADP    +  Pi   +   energy

The hydrolytic enzyme binds the ATP and catalyzes the reaction.  Two examples of hydrolytic enzymes within the muscle are:

The myosin head functions as a hydrolytic enzyme when it hydrolyzes ATP into ADP and Pi.  The energy released is used to prop the myosin cross bridge up into its high energy position.

The calcium ion pump which actively transports calcium ions back into the sarcoplasmic reticulum will act as a hydrolytic enzyme when it hydrolyzes ATP into ADP and Pi. The energy released is used to change the shape of the pump allowing the calcium ions to go back into the SR.

During the reaction, the water (shown in blue) breaks the high energy bond between the last two phosphate groups.  The water splits apart and the OH from the water ends up on the inorganic phosphate (sometimes abbreviated Pi) and the other H from the water goes onto the phosphate group which remains attached to the ADP. 

ADP is called adenosine diphosphate because only two phosphate groups remain on it. 

The energy contained in the bond between the last two phosphates on ATP has been released and is shown here as a glowing "E".  There is still one additional high energy bond left in the ADP.   (That high energy bond will not be important in this module.)

The energy released from the ATP hydrolysis will be used to

Disconnect the myosin cross bridge from the binding site on actin at the conclusion of a power stroke.

Energize the power stroke of the myosin cross bridge.

Energize the calcium ion pump which actively transports calcium ions back into the sarcoplasmic reticulum.

Page 6.  Dehydration Synthesis of ATP

This animation shows the dehydration synthesis of ATP.  It is called "dehydration synthesis" because water is removed (dehydration) and a bigger molecule is synthesized from two smaller ones.  Some textbooks call this process "condensation" because a water molecule is released.

Summary of the dehydration synthesis of ATP:

ADP      +      Pi       + energy            ATP       +      H2O  

The synthetic enzyme binds the ADP and catalyzes the reaction.  During the reaction, water (shown attached to the ADP and phosphate groups in blue) splits off and the inorganic phosphate (Pi) attaches to the ADP to form ATP.

This process requires energy since a high energy bond is formed.  The energy is shown here as a glowing yellow ball which appears.  One of the main functions of this section is to examine where that energy comes from.

Page 7.  ATP as "Energy Currency"

Page 8.  Overview of "Energy Currency"

Muscle cells synthesize ATP these three ways:

1. Hydrolysis of creatine phosphate

2. Glycolysis

3. The Krebs cycle & oxidative phosphorylation

Page 9.  Creatine Phosphate

The immediate source of energy for rebuilding ATP is the high energy molecule creatine phosphate.  The phosphate in  creatine phosphate, can be transferred to ADP to form ATP in a process called substrate phosphorylation.  However, there isn't much creatine phosphate stored in muscle cells.

 

Page 10.  Sources of Glucose

Two sources of glucose to muscles:

1. Blood glucose.

2. Breakdown of glycogen into glucose within the muscle cell.

Page 11.  Glycolysis

Summary of the process of glycolysis:

     

Page 12.  Anaerobic Pathway: Lactic Acid

Fill in the empty boxes to show glycolysis and the anaerobic pathway:

 

Page 13.  Sources of Oxygen

The oxygen needed for aerobic metabolism is available to muscle cells either directly from the blood or it can be stored in an oxygen binding protein called myoglobin.

Page 14.  Aerobic Pathway

Fill in the empty boxes to show the aerobic pathway:

 

 

Page 15.  Summary of ATP Production

This animation summarizes the three processes for producing ATP:

Creatine phosphate pathway

Glycolysis/anaerobic pathway

Aerobic pathway

It also reminds us that ATP is needed by the muscle cell for the power stroke of the myosin cross bridge, for disconnecting the cross bridge from the binding site on actin, and for transporting calcium ions back into the SR.

Page 16.  Creatine Phosphate "Factory"

This animation dramatically illustrates this process:

     

Page 17.  Glycolysis "Factory"

This animation dramatically illustrates the process of glycolysis from glycogen:

Page 18.  Anaerobic Pathway "Factory"

This animation dramatically illustrates lactic acid formation:

Notice how some of the lactic acid stays in the muscle, and some goes back out into the blood.  The lactic acid that stays in the muscle, decreases the pH of the muscle and contributes to the muscle fatigue.

Page 19.  Conversion to Acetyl CoA

This animation shows pyruvic acid entering the mitochondria in the presence of oxygen and its conversion to acetyl CoA:

Page 20.  Aerobic Respiration "Factory"

This animation illustrates aerobic respiration.  Pyruvic acid enters the mitochondria and is converted to acetyl CoA.  The Acetyl CoA enters the Krebs cycle and 36 ATPs per glucose are produced during oxidative phosphorylation.  The by-products are carbon dioxide and water:

Page 21.  Review of ATP "Factory"

This page allows the you to go back and review.  

Page 22.  Comparison of ATP Production

This animation compares ATP production via the three different pathways:

Hydrolysis of creatine phosphate: 1 ATP per creatine phosphate molecule

Glycolysis: 2 ATP per glucose

Krebs cycle & oxidative phosphorylation:  36 ATP per glucose molecule

Creatine phosphate and anaerobic metabolism can provide short bursts of ATP quickly but only with aerobic respiration (Krebs cycle and oxidative phosphorylation) will enough ATP be produced to provide sustained, long-duration muscle activity.

Page 23.  Recovery and Resting

After the exercise period is concluded, the muscle needs to restores the creatine phosphate, glycogen, and oxygen levels.  It also needs to use up excess lactic acid which may have accumulated during exercise.  This is sometimes called the "oxygen debt".

Fill in the blanks in this diagram as you view the animation on paying back the "oxygen debt":

Converting lactic acid back into pyruvic acid, which can now aerobically produce ATP (1). 

The ATP re-phosphorylates creatine into creatine phosphate (2).

Glucose enters the cell from the blood and forms glycogen (3).

Oxygen enters the cell from the blood and reattaches to myoglobin (4).

 

Page 24.  Metabolic Variations of Muscle Fiber Types

There are two types of muscle cells within a given muscle, white muscle fibers and red muscle fibers, which differ in size, coloration and metabolism.  

Page 25.  Features of White Muscle Fibers

Characteristics of white muscle fibers:

Large in diameter

Light in color due to reduced or absent myoglobin

Surrounded by only a few capillaries

Have relatively few mitochondria

Have a high glycogen content

Synthesize ATP mainly by glycolysis

Page 26.  Metabolism in White Muscle Fibers

Metabolic characteristics of white muscle fibers:

Use glycolysis, which synthesizes ATP quickly, resulting in fast contractions.

Allow for power contractions due to large numbers of myofilaments because they have a large diameter. 

They fatigue rapidly due to build-up of lactic acid and depletion of glycogen.

They are well suited for activities requiring power and speed for a short duration.

White muscle fibers are also called "fast-twitch glycolytic fibers."

Page 27.  Features of Red Muscle Fibers

Characteristics of red muscle fibers:

Half the diameter of white muscle fibers

Dark red in color due to a large quantity of myoglobin

Surrounded by many capillaries

Have many mitochondria

Have a low glycogen content

Synthesize ATP mainly by the Krebs cycle and oxidative phosphorylation

Page 28.  Metabolism in Red Muscle Fibers

Metabolic characteristics of red muscle fibers:

Use Krebs cycle and oxidative phosphorylation, which synthesizes ATP relatively slowly compared to glycolysis, resulting in prolonged contractions.

They are fatigue resistant.

They are well suited for activities requiring endurance and continuous contraction.

Red muscle fibers are also called "slow-twitch oxidative fibers".

Page 29.  Comparison of Muscles

Individuals that engage in fast, intense, sporadic activities, such as sprinting, tend to have more white, fast twitch, fatigue-prone fibers.  Individuals the engage in slower, longer muscular activities, such as jogging, have more red, slow twitch, fatigue resistant fibers.

Page 30.  Summary

ATP must be synthesized in muscle cells to replace ATP used for muscle contraction.

ATP is synthesized by hydrolysis of creatine phosphate, glycolysis, and the Krebs cycle and oxidative phosphorylation.

White muscle fibers mainly use glycolysis for synthesizing ATP; these fibers are quick and powerful, but fatigue rapidly.

Red muscle fibers mainly use the Krebs cycle and oxidative phosphorylation for synthesizing ATP; these fibers are fatigue resistant and have a high endurance.

Questions          Answers

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