Muscle Metabolism

Why Do We Need All

That ATP?

Animal Locomotion

What are the advantages of locomotion?

motilesessile

Lots of ways to get around…

Lots of ways to get around…

mollusk mammalbird reptile

Lots of ways to get around…

bird arthropodmammal bird

Where is ATP needed?

3

4

12

1

1

1

Cleaving ATP ADP allows myosin head to bind to actin filament

thin filament(actin)

thick filament(myosin)

ATP

myosin head

formcrossbridge

binding site

So that’s where those

10,000,000 ATPs go!Well, not all of it!

ADP

releasecrossbridge

shortensarcomere

1

How it all works…• Action potential causes Ca2+ release from SR

– Ca2+ binds to troponin

• Troponin moves tropomyosin uncovering myosin binding site on actin

• Myosin binds actin– uses ATP to "ratchet" each time– releases, "unratchets" & binds to next actin

• Myosin pulls actin chain along• Sarcomere shortens

– Z discs move closer together

• Whole fiber shortens contraction!• Ca2+ pumps restore Ca2+ to SR relaxation!

– pumps use ATP

ATP

ATP

Fueling Muscle Contraction • ATP is the immediate

source of energy for muscle contraction. Although a muscle fiber contains only enough ATP to power a few twitches, its ATP "pool" is replenished as needed.

3 sources of high-energy phosphate to keep the ATP pool filled. 1. creatine phosphate 2. glycogen 3. cellular respiration in the mitochondria of the fibers.

Creatine phosphate

• The phosphate group in creatine phosphate is attached by a "high-energy" bond like that in ATP.

• Creatine phosphate + ADP ↔ creatine + ATP

• The pool of creatine phosphate in the fiber is about 10 times larger than that of ATP and thus serves as a modest reservoir of ATP.

2-D cross-sectional view of glycogen. A core protein of glycogenin is surrounded by branches of glucose units. The entire globular granule may contain approximately 30,000 glucose units.[1]

Skeletal muscle fibers contain about 1% glycogen.

Glycogen: storage of “sugar”?

http://en.wikipedia.org/wiki/Glycogen

Glycolysis

glucose pyruvate2x6C 3C

In thecytosol?

Why doesthat make

evolutionarysense?

That’s not enoughATP for me!

• Breaking down glucose – “glyco – lysis” (splitting sugar)

– ancient pathway which harvests energy• where energy transfer first evolved• transfer energy from organic molecules to ATP• still is starting point for ALL cellular respiration

– but it’s inefficient • generate only 2 ATP for every 1 glucose

– occurs in cytosol

Glycolysis summary endergonicinvest some ATP

exergonicharvest a little ATP & a little NADH

net yield2 ATP2 NADH

4 ATP

ENERGY INVESTMENT

ENERGY PAYOFF G3P

C-C-C-P

NET YIELD

like $$in the bank

-2 ATP

recycleNADH

Reversible process once O2 is available,

lactate is converted back to pyruvate by the liver

Lactic Acid Fermentationpyruvate lactic acid

3C 3CNADH NAD+

Count thecarbons!

O2

animalssome fungi

back to glycolysis

Why does hurt after you’ve worked out? There are a couple of theories, although scientists still aren't exactly sure of what causes Delayed

Onset Soreness (DOMS), which is the soreness you feel a few hours to even a day or two after you workout.

1. when you work your muscles beyond what they are used to, you create microscopic tears in the muscle tissue. The more work you perform, the more tears you create. Also, when you perform exercises where you emphasize the eccentric contraction (basically resisting the weight as it's lowered), these tears are increased.

This is okay, because your body will repair this damage and your muscles will actually become stronger because of it. However, it can be uncomfortable for some people -- especially if you aren't well-conditioned.

2. There is also a theory that waste products -- particularly lactic acid -- that are created during exercise build up in the muscle and cause pain until the lactic acid has been purged by the body. This theory, however is under fire because the body typically flushes lactic acid fairly quickly. Lactic acid build-up is actually responsible for the "burn" you feel in your muscle when you work it (especially at high reps), versus the muscle tenderness of DOMS.

http://www.sportsinjurybulletin.com/arch…http://www.sciam.com/article.cfm?id=why-…

• 2 years ago

http://answers.yahoo.com/question/index?qid=20080210094842AAiEGg9

• The muscle fiber can degrade this glycogen by glycogenolysis producing glucose-1-phosphate.

• The liver is the main storage • of glucose and is controlled• by insulin and glucagon• **** Negative feedback and Homeostasis

How do we get glucose fast?

Energy accounting of glycolysis

• Net gain = 2 ATP + 2 NADH– some energy investment (-2 ATP)– small energy return (4 ATP + 2 NADH)

• 1 6C sugar 2 3C sugars

2 ATP 2 ADP

4 ADP

glucose pyruvate2x6C 3C

All that work! And that’s all

I get?ATP4

2 NAD+ 2 Butglucose has

so much moreto give!

Glycolysis: summary

1. Glycogen enters glycogenolysis producing glucose fast

2. Yields 2 ATP for each pair of lactic acid molecules produced

3. Not much, but enough to keep the muscle functioning if it fails to receive sufficient oxygen to meet its ATP needs by respiration.

4. However, this source is limited and eventually the muscle must depend on cellular respiration.

Cellular respiration is required for• to meet the ATP needs of a muscle engaged in

prolonged activity (thus causing more rapid and deeper breathing)

•

• afterwards to enable the body to resynthesize glycogen from the lactic acid produced earlier (deep breathing continues for a time after exercise is stopped).

• The body must repay its oxygen debt.

http://breathing.com/tests.htm

Cellular respiration

2 ATP 2 ATP ~36 ATP+ +

~40 ATP

It takes more time to produce ATP through respiration

: glucose has to split in the cytosol and then get into the mitochondria

Go through kreb’s cycle and then through etc

Finally make 34 ATP if Oxygen is present

So why is respiration the last method muscles use to get the energy they need if it has the biggest gain?

http://www.nismat.org/physcor/energy_supply.html

Fig. 50-37

Body mass (g)

Running

Swimming

Flying

Ener

gy c

ost (

cal/k

g•m

)

102

103

10

1

10–1

10–3 1061

RESULTS

Type I vs. Type II Fibers

Type 1 : slow twitchType 2: fast twitch

Reality we are comprised of both

• rich in myoglobin (red in color= the "dark" meat of the turkey)

• activated by small-diameter, thus slow-conducting, motor neurons

• dominant in muscles used in activities requiring endurance (leg muscles) and those that depend on tonus, e.g., those responsible for posture

1. loaded with mitochondria and 2. depend on cellular respiration for ATP production 3. fatty acids the major energy source 4. resistant to fatigue

Type I Fibers also known as "slow-twitch" fibers

Unlike hemoglobin, Mb does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only

Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve.

High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer.

Myoglobin

is the primary oxygen-carrying pigment of muscle tissues.

SO WHY DO MUSCLES NEED Mb WHEN THEY HAVE Hb?

http://en.wikipedia.org/wiki/Myoglobin

When meat is cooked, some of the proteins in it denature and become opaque, turning red meat pink.  At 60 degrees C, the myoglobin itself denatures and

becomes tan-coloured, giving well done meat a brownish-grey colour.  Freezing for long periods of time

can also denature the myoglobin.Finally, curing meat can cause other molecules to bond to myoglobin.  Nitrite, used in cured meats like ham and bacon, reacts to form nitric oxide.  Myoglobin bonded to nitric oxide is pink in colour.  Smoking or barbequeing

meat can also turn it pink‚ nitric oxide (named Molecule of the Year in 1992) is the culprit again.  This is the

characteristic smoke ring‚ of smoked and barbequed meats that is prized by barbeque aficionados.

Most of raw meat's colour comes from a pigment called myoglobin, which is related to hemoglobin and binds oxygen to transport it around the cell.  Myoglobin, like hemoglobin, contains a heme group (pictured above) which contains a central iron atom, usually in the +2 oxidation state.  The colour of myoglobin is determined by whatever the iron atom is bonded to:  if it's bonded to an O2 molecule, the myoglobin is bright red, whereas in the absense of oxygen it bonds to water and is a purple colour.  If the iron atom becomes oxidized, or loses an electron, the myoglobin turns brown.  This can happen after a prolonged time without access to oxygen, or in an acidic environment.

Type IIb Fibers

• few mitochondria • rich in glycogen and • depend on creatine phosphate and glycolysis for ATP

production • fatigue easily with the production of lactic acid • low in myoglobin hence whitish in color (the white meat

of the turkey) • activated by large-diameter, thus fast-conducting, motor

neurons • also known as "fast-twitch" fibers • dominant in muscles used for rapid movement, e.g.,

those moving the eyeballs.

Fast twitch & slow twitch muscles

• Slow twitch muscle fibers– contract slowly, but keep going for a long

time• more mitochondria for aerobic respiration • less SR Ca2+ remains in cytosol longer

– long distance runner– “dark” meat = more blood vessels

• Fast twitch muscle fibers– contract quickly, but get tired rapidly

• store more glycogen for anaerobic respiration – sprinter– “white” meat

Muscle limits• Muscle fatigue

– lack of sugar• lack of ATP to restore Ca2+ gradient

– low O2• lactic acid drops pH which

interferes with protein function– synaptic fatigue (failure of nerve impulse)

• loss of acetylcholine

• Muscle cramps– build up of lactic acid – ATP depletion– ion imbalance

• massage or stretching increases circulation

Recovery: oxygen consumption after exerciseIncreased breathing rate – enhanced O2 delivery

• “oxygen debt”: add O2 over and above O2 consumed when resting

• 1. be able to convert lactic acid back to glycogen (liver) • 2. resynthesize Cp and ATP• 3. replace O2 removed from Mb

Use O21. Increased body temp = inc. chem rate of reaction = inc.

ATP metabolism2. Heart muscles work harder3. Tissue repair at increased rate

Does Lance Armstrong break the rules?

Physical attributes1. an aerobic capacity of 83.8 mL/kg/min (VO2 Max),[9][10] higher than the average

person (40-50), but lower than other Tour De France winners, Miguel Indurain (88.0, although reports exist that Indurain tested at 92-94) and Greg LeMond

(92.5).[11] 2. He has a resting heart rate of 32-34 beats per minute (bpm) with a maximum heart

rate of 201 bpm.[12]

http://en.wikipedia.org/wiki/Lance_Armstrong

Blood doping?

http://whyfiles.org/090doping_sport/3.html