Estimated amimo acids contribute 5-15% of energy during prolonged exercise Because energy demands are so high during exercise, a small percentage is still substantial Amino acids are essential to integrity of skeletal muscle, their use for energy is of concern

1. Protein and Amino Acid
Metabolism

2. Protein metabolism during exercise typically
ignored, why should we care?
 Estimated amimo acids contribute 5-15% of
energy during prolonged exercise
 Because energy demands are so high during
exercise, a small percentage is still substantial
 Amino acids are essential to integrity of skeletal
muscle, their use for energy is of concern

3. Skeletal Muscle
 ~ 40 % of body weight
 Second largest source of stored energy (fat
is first)
– Glycogen
– Amino acids

4.  Skeletal muscle is composed of three
sources of amino acids
– Free amino acid pool
– Contractile protein*
– Non-contractile protein
*Contractile proteins are proteins that mediate sliding
of contractile fibres (contraction) of a cell's cytoskeleton, and
of cardiac and skeletal muscle.
Actin filaments are the major components of this network.
Other contractile proteins interact with these filaments to
create structural rigidity and movement.

5. Free Amino Acid Pool
 Free amino acids can come from plasma or
muscle
 Muscle due to it’s mass contains ~75% of
the total body free AA
 Still, free AA thought to contribute only
~1% of metabolically active AA

6. Non-contractile Protein
 Tyrosine and phenylalanine used as
indicators of non-contractile protein
degradation
 Magnitude of appearance proportional to
intensity and duration
 Animal studies have demonstrated up to
25% degradation during prolonged exercise

7. Contractile Protein
 3-methyl histidine (3-MH) most common
indicator of metabolism
 3-MH excretion reduced during exercise
and elevated afterwards
 Indicates contractile protein spared during
exercise, but not after (bi-phasic)
3-Methylhistidine

8.  This biphasic response depends on type of
exercise and intensity or duration
 Following light intensity endurance exercise
3-MH is not elevated during recovery
– Elevated following hi-intensity or prolonged
light intensity though
 In animals, 3-MH elevated after eccentric
exercise

9. 3-MH degradation is suppressed
during exercise
 The liver can contribute significant amounts
of amino acids to the total body pool
 Some of the 3-MH degradation is believed
to come from this source
 In studies using biopsies, it appears as
though 3-MH degradation is suppressed
during exercise

10. Amino Acid Metabolism in
Muscle
 Six amino acids can be metabolized by
muscle
– Alanine
– Aspartate
– Glutamate
– BCAA

11. BCAA??
 Branched Chain Amino Acids
 Isoleucine
 Leucine
 Valine
 Important sources of Kreb’s intermediates under
certain conditions

12. Transamination
It is a chemical reaction that transfers an amino group to a
ketoacid to form new amino acids. This pathway is
responsible for the deamination of most amino acids.
 First step in BCAA metabolism
 Donation of NH3 to form glutamate +
BCOA (Benzyl Co-enzyme A)
 BCOA can then form Acetyl-CoA or
Succinyl-CoA
– BCOA can also leave and go to liver

13. Transaminase
A transaminase is a type of enzyme whose activity is frequently measured, as
part of a standard series of tests, to determine liver function. There are a
number of different types of transaminases, but the two commonly measured
medically are alaninetransaminase (ALT) and aspartate transaminase (AST).
ALT is primarily localized to the liver and is considered a more specific test for
liver damage. ALT and AST are normally contained within the liver, but if the
organ is damaged, they are released into the bloodstream. As a result, their
levels in the blood are likely to be elevated if there is liver injury.
They may, however, be elevated under other conditions, including the cases
of thyroid disease, diabetes, and heart disease.
Many factors can cause the levels of these enzymes to vary. Men and women
have different levels, with men having higher amounts, and they are even
higher for African-American men than Caucasian men. Taking certain
medications and herbs may cause an increase in levels. A slight increase in level
activity will usually be followed by further diagnostic tests, since it could be
benign or indicate a severe condition.

14. BCAA Transdeamination
Venous
BCOA
NH3

15. Glutamate Central to
AA Metabolism
PNCGlutamate is a
powerful excitatory
neurotransmitter
that is released by
nerve cells in the
brain. It is
responsible for
sending signals
between nerve
cells, and under
normal conditions
it plays an
important role in
learning and
memory.
(Perinucleolar
Compartment)

16. Amino Acid Oxidation During
Exercise
 Skeletal muscle can utilize Ala, Asp, Glu
and the BCAA
 Ala released from muscle consistently for
gluconeogenesis
 Asp donates NH3 for reamination of IMP to
AMP + fumarate (TCA)

17.  ~4 % BCOADH active in muscle at rest
 Liver BCOADH completely active regardless
( of branched chain oxoacid dehydrogenase (BCOADH)
 At rest
– BCAA deaminated >> BCOA in muscle and sent
to the liver for oxidation

18. AA as Energy Source in
Skeletal Muscle
 Oxidation of BCAA yield between 32-43
ATP
– Comparable to complete oxidation of glucose
 AA contribute up to 18 % energy during
prolonged exercise
 BCOADH shown to increase activity up to
66 % in rodents Skeletal muscle

19. Measuring AA Flux from
Muscle
 At rest net efflux of AA from leg muscle
– Muscle releasing AA
 During exercise net uptake
– Prolonged exercise results in release from liver
(BCAA)

20. Evidence
 Mclean et al.- no net accumulation of AA in blood or
muscle
– Indicates skMc uptake and oxidation
 Rennie et al. – during exercise significant drop in efflux of
BCOA
– BCAA being oxidized in muscle
 Henderson et al. – 13 C leucine
– Oxidation to 13CO2
– Showed oxidation proportional to metabolic rate
– Dependent upon intensity and duration

21. What’s all this mean??
 During exercise amino acids will be
oxidized
 Rate of oxidation depends on intensity and
duration of the activity
 Long duration, intense activities will result
in high rates of AA oxidation
– Marathon, bike race, triathlon

22. Remember AMP Deamination?
 AMP >> IMP* + NH3
 Purposes
– ATP/ADP ratio
– Prevention of adenine nucleotide loss
– Production of ammonia to buffer H+
– Regulation of carbohydrate metabolism
 PFK and IMP* activation of PHOS
(*intermediate ribonucleoside monophosphate in purine
metabolism)
*Inosinic acid or inosine monophosphate (IMP) is a
nucleoside monophosphate. ... Important derivatives of inosinic
acid include purine nucleotides found in nucleic acids and
adenosine triphosphate, which is used to store chemical energy in
muscle and other tissues.
Chemical formula: C10H13N4O8P E number: E630 (flavour enhancer)
(Adenosine Monophosphate)

23. Ammonia as a buffer??
 NH3 can accept a proton
 NH3 + H+  NH4+
 Probably not physiologically significant

24. Purine Nucleotide Cycle
 Reaminates IMP to AMP
 Asp + GTP  Fumarate + NH3
 NH3 can be used to reaminate IMP
 Fumarate can be used in the Kreb’s cycle

25. Summary of AA Metabolism for Aerobic
Intermediates

26. Infuence of Carbohydrates
 Depletion of glycogen prior to exercise
results in elevated plasma NH3 levels
 Plasma NH3 levels lower during prolonged
exercise when subjects consume CHO

27.  If glycogen is depleted using prior exercise
and diet, plasma BCAA are elevated
 During the subsequent exercise bout,
plasma BCAA significantly reduced
 Indicates muscle is taking up and oxidizing
BCAA

28. Influence of FFA
 Infusion of FFA during leg exercise at 80 %
workmax
 Arterial concentration of several AA acids
reduced relative to control
 Net release of NH3 ~ half of control

29. Ketones
 Infusion of ketones has consistently been
shown to reduce leucine oxidation
Ketone bodies are water-soluble
molecules that are produced by the
liver from fatty acids during
periods of low food intake,
carbohydrate restrictive diets,
starvation, prolonged intense
exercise
Ketones are the result of the body
burning fat for energy or fuel. For a
person with diabetes, ketonesare
often the result of prolonged high
blood sugar and insulin deficiency.
Without the right amount of insulin,
glucose starts to build up in the
blood stream and doesn't enter the
cells.

30. Influence of Amino Acids
 When AA are infused or ingested plasma AA
will rise
 BCAA will be preferentially taken up by
muscle and pass by the liver…..ultimately.....
 AA oxidation will increase