(Skeletal) muscles and metabolic communication
In order to stay healthy, it’s important our
bodies remain in homeostasis. Organs
have to coordinate to achieve this in
varying conditions (exercising, fasting,
eating, etc). The liver is responsible for
most of the metabolic control. But it’s
usually not one organ who does one thing,
but a combination of different organs that
work together.
Organs do not only help each other, but
also have very different metabolic states
of their own.
Skeletal muscles consist of large, elongated cells with
various nuclei. One cell is a myofiber, which consists of
myofibrils, which is made up of sarcomeres. These have
thick filaments (with myosin heads) and thin filaments
(actin) that slide into each other on contraction.
Contraction in order of events:
1. Action potential arrives at the Neuromuscular junction; when the depolarization
wave arrives at this point, neurotransmitters are released into the synapse.
These neurotransmitters are picked up by the muscle cell, which results in an
influx of calcium from the extracellular fluid and intracellular store.
2. Calcium is released from the sarcoplasmic reticulum. The sarcoplasmic
reticulum is a specialized form of the endoplasmatic reticulum that serves as a
calcium storage. The sarcoplasm is low in calcium but the sarcoplasmic
reticulum is high in calcium. If the depolarization wave arrives at the terminal,
the sarcoplasmic reticulum released that calcium into the sarcoplasm.
3. This calcium then binds to troponin.
4. Troponin changes shape, which results in
the myosin-binding site being exposed by
tropomyosin.
5. Myosin heads attach to those active sites,
6. Myosin heads pivot,
7. The filaments slides ~10 nm, into each other.
8. ATP binds myosin heads on the ATP-binding site. This ATP is hydrolysed, which
means that ATP is converted to ADP + phosphate; the energy that is released
forms the energy for the next stroke.
9. Myosin heads detach,
10. Myosin heads return to pre-pivot position.
11. If calcium remains, go to step 3.
ATP is needed to make the contraction happen. Ca2+ is needed to let the contraction
happen.
,Relaxation in order of events:
1. Calcium is actively removes,
2. Tropomyosin re-‘covers’ active sites,
3. Filaments passively slide back.
ATP is needed to detach the myosin heads from the actin; when a person dies, the ATP
levels deplete quickly. Without ATP these myosin heads are frozen in place, which
results in rigor mortis.
Muscles often consist of different types of
fibre. Some are very rich in mitochondria
(dark); these are called slow oxidative
fibres. They are surrounded by many
capillaries.
Fast glycolytic fibres have a large
diameter, but contain few mitochondria.
Finally there are fast oxidative glycolytic
fibres; they have abundant mitochondria
and are intermediate in diameter and
abundance of capillaries. So even without
one tissue, different types of fibres are
important to make everything work.
Short intense physical activities, such as a sprint, require rapid increase in ATP
consumption, which quickly depletes the ATP storage. The storage in muscles lasts
around 2 seconds. There are several systems to replenish this ATP. It can be replenished
quickly by a high energy intermediate called phosphocreatine; these stores last about
20 seconds. After this, the muscle has to switch to glycolysis.
This is different when running a marathon, which requires very long physical activity. In
this case, the muscle also has to switch, but it will start by using ATP through anaerobic
glycolysis. They will then switch to aerobic glycolysis as well as oxidation of fatty acids
and few amino acids. A limiting
factor here is how long it takes for
enough O2 to arrive at the muscle
to maintain oxidative
phosphorylation.
→ First, muscles will use ATP
hydrolysis, which only lasts a
short while. Then, they use
phosphocreatine to replenish
ATP, but this also does not last
very long. At that point, the
muscle needs to start making it’s
own energy. First, it does this through anaerobic glycolysis because there is not
sufficient oxygen present. The oxygen to the muscle will be increased with higher blood
pressure during exercise, which will then result in aerobic carbohydrate degradation.
, Phosphocreatine cycle
During high intensity activities, ATP is rapidly used and becomes
ADP. Phosphocreatine then quickly donated it’s phosphate back
to the ADP, which is a fast way of generating ATP.
The creatine is then re-phosphorylated with the help of the
enzyme creatine kinase. There are two creatine kinases, one
mitochondrial and one cytosolic. So, creatine can be re-
phosphorylated in the mitochondria, where ATP is largely
present, after which the phosphocreatine goes back to the
cytoplasm. It can also happen in the cytoplasm itself; in resting
conditions, when there is also plenty ATP present in the cytosol.
This is also one of the ways that the ATP that is present in the
mitochondria gets brought to the cytosol.
ATP in the cell is never depleted. In the
magnetic resonance spectrum, it is
shown that the levels of (the 3
phosphates in) ATP don’t fluctuate much, and are independent
of whether the body is at rest, exercise or recovering; the ATP
levels stay the same. What changes, are the levels of
phosphocreatine, which is high at rest
and recovery, but largely depleted at exercise.
A waste product of creatine is creatinine; creatinine is the
hydrolysis product of creatine and phosphocreatine. The
percentage that spontaneously hydrolyses (2,6% or 1,1% per
day) is very low. This creatinine is usually excreted by the urine;
the kidney usually clears this very efficiently. This is also used as
a way to evaluate kidney health; upon renal defects, creatinine
levels in the blood rise above the normal range (0.8-1.4).
Phosphocreatine biosynthesis
Phosphocreatine can be synthesized from amino acids (mainly in the kidney and the
liver). Creatine is created from glycine, arginine and methionine.
We can also take up creatine from meat and dairy products; for vegans, de novo
synthesis of creatine consumes a substantial amount of glycine, arginine and
methionine, as plants do not contain creatine.
The synthesis mostly takes place in the liver and the kidney, but muscles have a
dedicated transport system for creatine from the blood, so they can take up the largest
share of creatine in our body.
, Metabolic adaptation in the exercising
muscle
When exercising, the muscle first uses the
available ATP, then replenishes this
through phosphocreatine hydrolysis. After
that, it will use anaerobic glycolysis.
Anaerobic respiration is only used to
bridge the gap until enough oxygen can
reach the muscles. The end product of
this is lactate. The lactate concentration in
the blood can thus be used as a readout of
how physically fit someone is; the quicker
the body can switch to aerobic glycolysis,
the better it is for endurance.
Anaerobic respiration only gives 2 ATP per
molecule glucose, whereas aerobic respiration can give 30
ATP or more (depending on how it’s calculated).
Cori Cycle
The Cori cycle is one of the simpler communication paths
between the muscle and the liver. In the muscle, glycogen or
glucose is used, in anaerobic glycolysis, to produce lactate
and ATP. This lactate is often secreted to the blood. (Lactate
is acidic, and makes the environment more acidic). The liver
then takes up this lactate. During recovery, this is then
converted back to glucose by gluconeogenesis. This is then
shuttled back to the muscle, where it can be used again.
Glucose is the main energy source for muscle contraction.
Glycogen is the storage form of glucose.
For prolonged activity, the muscle can also burn fatty acids, ketone bodies and the
blood glucose which is replenished through the liver. It can however, also use amino
acids as a source of energy. This is best avoided, however, as amino acid breakdown
also includes myosin and actin, which would render the muscle ineffective. However,
there is some amino acid breakdown throughout the body.
In order to stay healthy, it’s important our
bodies remain in homeostasis. Organs
have to coordinate to achieve this in
varying conditions (exercising, fasting,
eating, etc). The liver is responsible for
most of the metabolic control. But it’s
usually not one organ who does one thing,
but a combination of different organs that
work together.
Organs do not only help each other, but
also have very different metabolic states
of their own.
Skeletal muscles consist of large, elongated cells with
various nuclei. One cell is a myofiber, which consists of
myofibrils, which is made up of sarcomeres. These have
thick filaments (with myosin heads) and thin filaments
(actin) that slide into each other on contraction.
Contraction in order of events:
1. Action potential arrives at the Neuromuscular junction; when the depolarization
wave arrives at this point, neurotransmitters are released into the synapse.
These neurotransmitters are picked up by the muscle cell, which results in an
influx of calcium from the extracellular fluid and intracellular store.
2. Calcium is released from the sarcoplasmic reticulum. The sarcoplasmic
reticulum is a specialized form of the endoplasmatic reticulum that serves as a
calcium storage. The sarcoplasm is low in calcium but the sarcoplasmic
reticulum is high in calcium. If the depolarization wave arrives at the terminal,
the sarcoplasmic reticulum released that calcium into the sarcoplasm.
3. This calcium then binds to troponin.
4. Troponin changes shape, which results in
the myosin-binding site being exposed by
tropomyosin.
5. Myosin heads attach to those active sites,
6. Myosin heads pivot,
7. The filaments slides ~10 nm, into each other.
8. ATP binds myosin heads on the ATP-binding site. This ATP is hydrolysed, which
means that ATP is converted to ADP + phosphate; the energy that is released
forms the energy for the next stroke.
9. Myosin heads detach,
10. Myosin heads return to pre-pivot position.
11. If calcium remains, go to step 3.
ATP is needed to make the contraction happen. Ca2+ is needed to let the contraction
happen.
,Relaxation in order of events:
1. Calcium is actively removes,
2. Tropomyosin re-‘covers’ active sites,
3. Filaments passively slide back.
ATP is needed to detach the myosin heads from the actin; when a person dies, the ATP
levels deplete quickly. Without ATP these myosin heads are frozen in place, which
results in rigor mortis.
Muscles often consist of different types of
fibre. Some are very rich in mitochondria
(dark); these are called slow oxidative
fibres. They are surrounded by many
capillaries.
Fast glycolytic fibres have a large
diameter, but contain few mitochondria.
Finally there are fast oxidative glycolytic
fibres; they have abundant mitochondria
and are intermediate in diameter and
abundance of capillaries. So even without
one tissue, different types of fibres are
important to make everything work.
Short intense physical activities, such as a sprint, require rapid increase in ATP
consumption, which quickly depletes the ATP storage. The storage in muscles lasts
around 2 seconds. There are several systems to replenish this ATP. It can be replenished
quickly by a high energy intermediate called phosphocreatine; these stores last about
20 seconds. After this, the muscle has to switch to glycolysis.
This is different when running a marathon, which requires very long physical activity. In
this case, the muscle also has to switch, but it will start by using ATP through anaerobic
glycolysis. They will then switch to aerobic glycolysis as well as oxidation of fatty acids
and few amino acids. A limiting
factor here is how long it takes for
enough O2 to arrive at the muscle
to maintain oxidative
phosphorylation.
→ First, muscles will use ATP
hydrolysis, which only lasts a
short while. Then, they use
phosphocreatine to replenish
ATP, but this also does not last
very long. At that point, the
muscle needs to start making it’s
own energy. First, it does this through anaerobic glycolysis because there is not
sufficient oxygen present. The oxygen to the muscle will be increased with higher blood
pressure during exercise, which will then result in aerobic carbohydrate degradation.
, Phosphocreatine cycle
During high intensity activities, ATP is rapidly used and becomes
ADP. Phosphocreatine then quickly donated it’s phosphate back
to the ADP, which is a fast way of generating ATP.
The creatine is then re-phosphorylated with the help of the
enzyme creatine kinase. There are two creatine kinases, one
mitochondrial and one cytosolic. So, creatine can be re-
phosphorylated in the mitochondria, where ATP is largely
present, after which the phosphocreatine goes back to the
cytoplasm. It can also happen in the cytoplasm itself; in resting
conditions, when there is also plenty ATP present in the cytosol.
This is also one of the ways that the ATP that is present in the
mitochondria gets brought to the cytosol.
ATP in the cell is never depleted. In the
magnetic resonance spectrum, it is
shown that the levels of (the 3
phosphates in) ATP don’t fluctuate much, and are independent
of whether the body is at rest, exercise or recovering; the ATP
levels stay the same. What changes, are the levels of
phosphocreatine, which is high at rest
and recovery, but largely depleted at exercise.
A waste product of creatine is creatinine; creatinine is the
hydrolysis product of creatine and phosphocreatine. The
percentage that spontaneously hydrolyses (2,6% or 1,1% per
day) is very low. This creatinine is usually excreted by the urine;
the kidney usually clears this very efficiently. This is also used as
a way to evaluate kidney health; upon renal defects, creatinine
levels in the blood rise above the normal range (0.8-1.4).
Phosphocreatine biosynthesis
Phosphocreatine can be synthesized from amino acids (mainly in the kidney and the
liver). Creatine is created from glycine, arginine and methionine.
We can also take up creatine from meat and dairy products; for vegans, de novo
synthesis of creatine consumes a substantial amount of glycine, arginine and
methionine, as plants do not contain creatine.
The synthesis mostly takes place in the liver and the kidney, but muscles have a
dedicated transport system for creatine from the blood, so they can take up the largest
share of creatine in our body.
, Metabolic adaptation in the exercising
muscle
When exercising, the muscle first uses the
available ATP, then replenishes this
through phosphocreatine hydrolysis. After
that, it will use anaerobic glycolysis.
Anaerobic respiration is only used to
bridge the gap until enough oxygen can
reach the muscles. The end product of
this is lactate. The lactate concentration in
the blood can thus be used as a readout of
how physically fit someone is; the quicker
the body can switch to aerobic glycolysis,
the better it is for endurance.
Anaerobic respiration only gives 2 ATP per
molecule glucose, whereas aerobic respiration can give 30
ATP or more (depending on how it’s calculated).
Cori Cycle
The Cori cycle is one of the simpler communication paths
between the muscle and the liver. In the muscle, glycogen or
glucose is used, in anaerobic glycolysis, to produce lactate
and ATP. This lactate is often secreted to the blood. (Lactate
is acidic, and makes the environment more acidic). The liver
then takes up this lactate. During recovery, this is then
converted back to glucose by gluconeogenesis. This is then
shuttled back to the muscle, where it can be used again.
Glucose is the main energy source for muscle contraction.
Glycogen is the storage form of glucose.
For prolonged activity, the muscle can also burn fatty acids, ketone bodies and the
blood glucose which is replenished through the liver. It can however, also use amino
acids as a source of energy. This is best avoided, however, as amino acid breakdown
also includes myosin and actin, which would render the muscle ineffective. However,
there is some amino acid breakdown throughout the body.
