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Protein and Amino Acid Protein and Amino Acid MetabolismMetabolism
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Protein metabolism during exercise Protein metabolism during exercise typically ignored, why should we typically ignored, why should we
care?care?Estimated amimo acids contribute 5-15% of
energy during prolonged exerciseBecause energy demands are so high during
exercise, a small percentage is still substantialAmino acids essential to integrity of skeletal
muscle, their use for energy is of concern
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Skeletal MuscleSkeletal Muscle
~ 40 % of body weightSecond largest source of stored energy (fat
is first)– Glycogen– Amino acids
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Skeletal muscle is composed of three sources of amino acids– Free amino acid pool– Contractile protein – Non-contractile protein
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Free Amino Acid PoolFree 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
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Non-contractile ProteinNon-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
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Contractile ProteinContractile Protein
3-methyl histidine (3-MH) most common indicator of metabolism
3-MH excretion reduced during exercise and elevated afterward
Indicates contractile protein spared during exercise, but not after
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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 thoughIn animals, 3-MH elevated after eccentric
exercise
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A brief noteA brief note
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
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Amino Acid Metabolism in Amino Acid Metabolism in MuscleMuscle
Six amino acids can be metabolized by muscle– Alanine– Aspartate– Glutamate – BCAA
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BCAA??BCAA??
Branched Chain Amino AcidsIsoleucineLeucineValineImportant sources of Krebs intermediates
under certain conditions
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TransaminationTransamination
First step in BCAA metabolismDonation of NH3 to form glutamate +
BCOABCOA can then form Acetyl-CoA or
Succinyl-CoA– BCOA can also leave and go to liver
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BCAA TransdeaminationBCAA Transdeamination
Venous
BCOA
NH3
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Glutamate Central to AA Glutamate Central to AA MetabolismMetabolism
PNC
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Amino Acid Oxidation During Amino Acid Oxidation During ExerciseExercise
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)
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~4 % BCOADH active in muscle at rest
Liver BCOADH completely active
regardless
At rest
– BCAA deaminated >> BCOA in muscle and
sent to the liver for oxidation
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AA as Energy Source in AA as Energy Source in Skeletal MuscleSkeletal Muscle
Oxidation of BCAA yield between 32-43 ATP– Comparable to complete oxidation of glucose
AA contribute uup to 18 % energy during prolonged exercise
BCOADH shown to increase activity up to 66 % in rodents Sk muscle
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Measuring AA Flux from Measuring AA Flux from MuscleMuscle
At rest net efflux of AA from leg muscle– Muscle releasing AA
During exercise net uptake– Prolonged exercise results in release from liver
(BCAA)
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EvidenceEvidence
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
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More EvidenceMore Evidence
Henderson et al. – 13 C leucine– Oxidation to 13CO2
– Showed oxidation proportional to metabolic rate
– Dependent upon intensity and duration
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What’s all this mean??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
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Remember AMP Remember AMP Deamination?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
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Ammonia as a buffer??Ammonia as a buffer??
NH3 can accept a proton
NH3 + H+ NH4+
Probably not physiologically significant
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Purine Nucleotide CyclePurine 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
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Summary of AA Metabolism Summary of AA Metabolism for Aerobic Intermediatesfor Aerobic Intermediates
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Infuence of CarbohydratesInfuence 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
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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 oxidizding BCAA
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Influence of FFAInfluence 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
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KetonesKetones
Infusion of ketones has consistently been
shown to reduce leucine oxidation
No data on NH3 or other amino acids
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Influence of Amino AcidsInfluence of Amino AcidsWhen AA are infused or ingested plasma
AA will rise
BCAA will be preferentially taken up by muscle and pass by the liver
AA oxidation will increase
Is this good or bad???