Types of exercise

Type 1 suited to aerobic exercise, mitochondria rich, good blood

supply, stores more TAG, resistant to fatigue, moderate glycolytic
cacpity, high oxidative capacity, slow myosin ATPases
Type 2 suited to anaerobic exercise, mitochondria poor, moderate
blood supply, stores more glycogen, easily fatigued, rapid myosin
ATPases, low oxidative capacity, high glycolytic capacity
Exercise types
Aerobic sustained for long periods, low moderate intensity e.g.
marathon
Anaerobic short duration, high intensity e.g. weight lifting/
sprinting
Sources of fuel
- Muscle and liver glycogen: used during fasting or exercise esp.
high intensity. Exhaustion coincides with depletion of muscle
glycogen.
- Plasma glucose: uptake increases during fed state, exercise and
after exercise
- Muscle and adipose TAG: usage increases during fasting and
exercise esp. low intensity
- Plasma lipoproteins: muscle secretes lipoprotein lipase during
fasting, and after exercise, to replenish TAG store.
- Ketone bodies: usage increases during very prolonged exercise,
or very prolonged fasting depends on supply by liver.

Muscle Metabolism in the Fed State

- insulin stimulates an increase in glucose uptake glycogenesis
and glycolysis increase, while fatty acid oxidation is inhibited
- liver senses high [glucose] uptake increases, used for synthesis
of glycogen/ TAG
- pancreas beta cells sense high [glucose] uptake increases,
insulin release stimulated
- insulin favours lipogenesis and inhibits lipolysis
Muscle Metabolism in the Fasting State (at rest)
- decrease in insulin causes decrease in glucose uptake in
muscles. Fatty acid oxidation increases. Amino acids may be
released
- pancreatic beta cells sense low [glucose] uptake decreases,
insulin release decreases
- Low insulin favours release of fatty acids
- Liver senses low [glucose] glucose is released from glycogen
stores and gluconeogenesis.
Muscle Metabolism during exercise
- glycogenolysis and glucose uptake increase. Uptake of fatty
acids and breakdown of TAG increase.
- Adrenaline stimulates glycogenolysis in liver, so glucose is
released. Lactate released by muscle is converted back to
glucose.
- Adrenaline favours release of fatty acids.
High Intensity Exercise
High intensity contractions require a high rate of ATP replenishment.
Glycolysis is the pathway most suited to this, due to its lack of
reliance on oxygen diffusion into the tissue.
Type II muscle fibres are recruited for these types of contractions. In
the five seconds before the rate of glycolysis can be increased, the
stores of phosphocreatine are used to replenish ATP, via creatine
kinase.
ADP is also used to replenish ATP via adenylate kinase. The AMP
produced is an allosteric effector for several enzymes.
Adenylate kinase catalyses the formation of ATP from ADP, and
helps to maintain the ATP: ADP ratio. This reactions also results in an
increase in [AMP].

This helps to maintain the ATP concentration, and the increase in

AMP is used as a signal that ATP production needs to increase.

[AMP] is therefore a sensitive indicator of the cells energy status.

AMP is an important allosteric effector.
Phosphocreatine
Phosphocreatine is an energy store that replenishes ATP in the first
5s of maximal exertion. It also acts as a more diffusible form of high
energy phosphate.

Skeletal muscle contains high levels of phosphocreatine, at 30mM,

compared to 7mM in other cell types.
As pH decreases (anaerobic glycolysis producing lactic acid), [ADP]
increases and reaction goes forward.
After exercise is over, adenylate kinase works to convert AMP to
ADP, so it can be converted to ATP, and phosphocreatine is
replenished from ATP.
Glucose availability: glucose needed for exercise, esp. high intensity
exercise for contracting muscles.
Breakdown of muscle glycogen stimulated by the activation of
glycogen phosphorylase.

Breakdown of liver glycogen is stimulated by a similar process.

Muscle contraction causes translocation of GLUT4 transporters to
the membrane, allow it to take up glucose from the blood. The
amount of glucose made available is affected by other factors, and
there is a limit to the rate glucose can be made available.
Phosphorylase kinase.
Phosphorylase kinase activates glycogen phosphorylase, and is itself
partially activated by calcium ions or phosphorylation, or maximally
activated by both.

In muscle, adrenaline stimulates PKA, while contractions are

associated with the release of calcium ions into the cytosol.
In the liver, glucagon stimulates PKA, adnrealine stimulates PKA ad
calcium release into the cytosol, supplying glucose for the muscles.
Upregulation of glycolysis
Apart from increasing the supply of glucose, the regulatory enzymes
of glycolysis must also increase their availability.

Hexokinase: inhibited by glucose 6 P, inhibition is relieved as the

rate of glucolysis is increased.
Phosphofructokinase 1: activated by the increase in AMP
(adenylate kinase). Any fructose 6 P buildup is converted to F2,6
bisP, a potent activator.
Pyruvate kinase: activated by the increase in AMP. Any buildup in
F1,6 bisP also activates it (feedforward activation)
The occurrence of fatty acid oxidation has a negative effect on the
rate of glycolysis, causing glycogen to last longer.
Phosphofructokinase 1
PFK is the central regulatory enzyme in glycolysis, because it
determines the activity of hexokinase and pyruvate kinase. ATP is a
substrate of PFK-1, but high [ATP] inhibits PFK-1

When [ATP] is high, and [phosphocreatine] is high, inhibition of PFK1 shuts down glycolysis. If fatty acids are being oxidized, citrate also
inhibits PFK-1.