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Muscle Metabolism
Why Do We
Need All
That ATP?
Animal Locomotion
What are the advantages of locomotion?
sessile
motile
Lots of ways to get around…
Lots of ways to get around…
mollusk mammal
bird reptile
Lots of ways to get around…
bird arthropod
mammal bird
Where is ATP needed?
binding site
thin filament
(actin)
myosin head
ADP
12
thick filament
(myosin)
ATP
So that’s
where those
10,000,000 ATPs go!
Well, not all of it!
form
cross
bridge
11
1
3
release
cross
bridge
Cleaving ATP  ADP allows myosin
1
head to bind to actin filament
shorten
sarcomere
4
How it all works…
• Action potential causes Ca2+ release from SR
– Ca2+ binds to troponin
• Troponin moves tropomyosin uncovering myosin
binding site on actin
ATP
• 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
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.
Glycogen: storage of “sugar”?
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.
http://en.wikipedia.org/wiki/Glycogen
Glycolysis
• Breaking down glucose
– “glyco – lysis” (splitting sugar)
glucose      pyruvate
2x 3C
6C
– 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
That’s not enough
ATP for me!
In the
cytosol?
Why does
that make
evolutionary
sense?
Glycolysis summary
endergonic
invest some ATP
ENERGY INVESTMENT
-2 ATP
ENERGY PAYOFF
G3P
C-C-C-P
4 ATP
exergonic
harvest a little
ATP & a little NADH
like $$
in the
bank
NET YIELD
net yield
2 ATP
2 NADH
animals
some fungi
Lactic Acid Fermentation
pyruvate  lactic acid

3C
NADH
3C
NAD+ back to glycolysis
 Reversible process
 once O2 is available,
lactate is converted
back to pyruvate by
the liver
Count the
carbons!
O2
recycle
NADH
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 buildup 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
How do we get glucose fast?
• 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
Energy accounting of glycolysis
2 ATP
2 ADP
glucose      pyruvate
2x 3C
6C
4 ADP
4 ATP
2 NAD+
2
• Net gain = 2 ATP + 2 NADH
All that work!
And that’s all
I get?
But
glucose has
so much more
to give!
– some energy investment (-2 ATP)
– small energy return (4 ATP + 2 NADH)
• 1 6C sugar  2 3C sugars
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
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
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
Fig. 50-37
Energy cost (cal/kg•m)
RESULTS
Flying
Running
102
10
1
Swimming
10–1
10–3
1
103
Body mass (g)
106
Type I vs. Type II Fibers
Type 1 : slow twitch
Type 2: fast twitch
Reality we are comprised of
both
Type I Fibers also known as "slow-twitch" fibers
1. loaded with mitochondria and
2. depend on cellular respiration for ATP
production
3. fatty acids the major energy source
4. resistant to fatigue
• 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
Myoglobin
is the primary oxygen-carrying pigment of muscle
tissues.
SO WHY DO MUSCLES NEED Mb WHEN
THEY HAVE Hb?
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.
http://en.wikipedia.org/wiki/Myoglobin
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
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.
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 exercise
Increased 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 O2
1. Increased body temp = inc. chem rate of reaction = inc.
ATP metabolism
2. Heart muscles work harder
3. Tissue repair at increased rate
Does Lance Armstrong break the rules?
Blood doping?
http://whyfiles.org/090doping_sport/3.html
http://en.wikipedia.org/wiki/Lance_Armstrong
Physical attributes
1. 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]