Describe the evolution of lactate metabolism from a historical perspective to current evidence.
Explain the lactate shuttle(s) and the Cori cycle.
Understand:
Why lactate increases with intense exercise.
The biochemical basis of how lactate does not cause fatigue.
What the lactate threshold is and why we might want to measure it.
At physiological pH (7.4), lactic acid almost completely dissociates into lactate and hydrogen ions (H+).
Lactic acid in muscle was historically thought to be the cause of muscle fatigue.
During intense exercise, both lactate and H+ increase in muscle.
This is associated with a drop in muscle pH from ~7.05 to ~6.5. [What is pH?]
Fatigue can ensue with pH drop to as little as ~6.9.
Frog muscles were stimulated to contract.
Lactate accumulated, and there was fatigue.
When fatigued muscles were put in an oxygen-rich environment, lactate disappeared.
During exercise under anaerobic conditions:
Fatigue occurs.
H+ increases.
Lactate is present.
Previously taught that with O2 you have pyruvate, and without O2 you have lactate.
Lactate:pyruvate ratio in resting muscle needs to be considered.
There is a rise in lactate at the beginning of exercise.
This is because there is an O2 deficit (hypoxia) in exercising muscle.
Stimulated unperfused frog muscle to contract. Lactate produced, O2 required to remove.
Theory: Lactate produced because of a lack of O2 in contracting muscle (anaerobic metabolism).
Main theories:
O2 deficit
O2 debt
It was believed that excess VO2 post-exercise was to “repay” the O2 deficit (i.e., get rid of La- produced as a result of the O2 deficit).
Believed that 20% La- was oxidised to provide ATP to convert the remaining 80% La- back to glycogen.
Anaerobic metabolism produces ATP, which produces lactate – a waste product.
After exercise, to get rid of this “waste product”, the lactate is converted to glycogen (stored CHO).
This led to the concept of anaerobic/lactate threshold in the 1960s and 70s by Wasserman and colleagues.
Lactate threshold = The exercise intensity where blood lactate increases exponentially.
Reflects the last point (i.e., exercise intensity) where lactate entry into and removal from the blood are balanced.
A useful measure?
Blood Lactate (BLa) and ventilation increases disproportionately to VO2.
Lack of O2 thought to increase anaerobic glycolysis and thus lactic acid.
Lactic acid doesn’t exist, so it dissociates to La- and H+ and were responsible for muscle acidosis.
The body attempts to buffer H+ resulting in increased CO2, a potent stimulus for respiration.
Lactate is transported to the liver in the venous system.
Converted to glucose in the liver through a form of gluconeogenesis.
During exercise, roughly 25% of lactate is removed through the Cori cycle.
Screening for alcohol.
The historical view was that glycolysis (involving the production of lactate) and aerobic metabolism were separate.
Work by Brooks around 2000 proposed new mechanisms of lactate metabolism.
Lactate (the product of glycolysis) is actually a substrate for aerobic metabolism.
Lactate can be moved around within the same cell and oxidised.
Components and processes include:
Sarcolemma
Glycogen
Glucose-6-Phosphate (G-6-P)
Lactate Transporter (LT)
Pyruvate
Glucose
Glycolysis (GL)
Tricarboxylic Acid cycle (TCA)
Carbon Dioxide (CO2)
Lactate Dehydrogenase (LDH)
Lactate can be moved to other cells and tissues to be oxidised.
Involves:
Type I and Type IIa muscle fibres
Monocarboxylate transporters (MCT1, MCT4)
Lactate acts as a potent signaling molecule in the body.
Lactate production increases as exercise intensity increases (rate of appearance (Ra)).
Lactate disappearance (Rd) does not increase to the same extent as the rate of appearance.
This leads to a net increase in blood (or muscle) lactate (Stanley et al., 1985).
Current evidence: O2 is available at the start of exercise.
But, there is an inability to utilise O2 in metabolic pathways and insufficient metabolic substrates at the start of exercise.
There is no oxygen deficit; La is produced as an integral part of aerobic metabolism.
Phosphocreatine resynthesis in muscle
Lactate removal
Elevated hormone levels
Elevated heart rate and breathing rate post-exercise
Elevated core body temperature
Restoration of O2 stores in muscle and blood
Correlation does not mean causation.
Force decreases as there is a decrease in intracellular pH.
But force recovers faster than the recovery in pH, suggesting a disconnect (Allen et al. 2008).
Lactate remains a useful measure to indicate the changes in metabolism with exercise.
Lactate is produced at rest.
The H+ produced as a result of lactic acid may not cause the reduction in pH (even if pH is a cause of fatigue).
Lactate may actually protect against acidosis (Robergs et al. 2004).
Lactate prevents pyruvate accumulation and supplies NAD(+) needed in phase 2 of glycolysis.
Lactate should not be seen as a glycolytic waste product nor as an acidifier.
Lactate; acidosis; and fatigue; are not equivalent in human physiology.
Determinants of exercise performance:
HR max
SV max
Capillary density
Q max
[Hb]; % SaO2
[Ca – Cv O2] max
VO2 max
Oxidative enzymes
% VO2max at LT
Running economy
Velocity at LT
Max velocity in distance running
The LT is worth measuring, even if we do not fully understand the mechanisms.
Start at 9 km/h or 60 W.
4 min per stage.
Increased intensity of 1 km/h or 20 W per stage.
30 s rest per stage to allow for blood sampling (treadmill only).
Lactate threshold is calculated from plotting intensity (speed, power) on the x-axis and blood lactate concentration on the y-axis.
A curve is fitted, and LT determined using an equation of choice.
MLSS = the highest blood La- and workload that can be obtained without continued blood lactate accumulation.
The blood La- concentration varies by < 1mmol/L during the last 20 mins of constant intensity exercise.
16 weeks of physical training in 8 male students.
There is a rightward shift in the blood lactate concentration curve.
Can work harder before starting to accumulate blood lactate.
Lactate is not a waste product and does not cause fatigue!
Lactate can be shuttled between and within cells – oxidised to produce ATP or converted to glycogen in the liver.
Produced from anaerobic metabolism but can be a substrate for aerobic metabolism.
Lactate can be an important performance measure.
Lactate Metabolism Notes
Describe the evolution of lactate metabolism from a historical perspective to current evidence.
Explain the lactate shuttle(s) and the Cori cycle.
Understand:
Why lactate increases with intense exercise.
The biochemical basis of how lactate does not cause fatigue.
What the lactate threshold is and why we might want to measure it.
At physiological pH (7.4), lactic acid almost completely dissociates into lactate and hydrogen ions (H+).
Lactic acid in muscle was historically thought to be the cause of muscle fatigue.
During intense exercise, both lactate and H+ increase in muscle.
This is associated with a drop in muscle pH from ~7.05 to ~6.5. [What is pH?]
Fatigue can ensue with pH drop to as little as ~6.9.
Frog muscles were stimulated to contract.
Lactate accumulated, and there was fatigue.
When fatigued muscles were put in an oxygen-rich environment, lactate disappeared.
During exercise under anaerobic conditions:
Fatigue occurs.
H+ increases.
Lactate is present.
Previously taught that with O2 you have pyruvate, and without O2 you have lactate.
Lactate:pyruvate ratio in resting muscle needs to be considered.
There is a rise in lactate at the beginning of exercise.
This is because there is an O2 deficit (hypoxia) in exercising muscle.
Stimulated unperfused frog muscle to contract. Lactate produced, O2 required to remove.
Theory: Lactate produced because of a lack of O2 in contracting muscle (anaerobic metabolism).
Main theories:
O2 deficit
O2 debt
It was believed that excess VO2 post-exercise was to “repay” the O2 deficit (i.e., get rid of La- produced as a result of the O2 deficit).
Believed that 20% La- was oxidised to provide ATP to convert the remaining 80% La- back to glycogen.
Anaerobic metabolism produces ATP, which produces lactate – a waste product.
After exercise, to get rid of this “waste product”, the lactate is converted to glycogen (stored CHO).
This led to the concept of anaerobic/lactate threshold in the 1960s and 70s by Wasserman and colleagues.
Lactate threshold = The exercise intensity where blood lactate increases exponentially.
Reflects the last point (i.e., exercise intensity) where lactate entry into and removal from the blood are balanced.
A useful measure?
Blood Lactate (BLa) and ventilation increases disproportionately to VO2.
Lack of O2 thought to increase anaerobic glycolysis and thus lactic acid.
Lactic acid doesn’t exist, so it dissociates to La- and H+ and were responsible for muscle acidosis.
The body attempts to buffer H+ resulting in increased CO2, a potent stimulus for respiration.
Lactate is transported to the liver in the venous system.
Converted to glucose in the liver through a form of gluconeogenesis.
During exercise, roughly 25% of lactate is removed through the Cori cycle.
Screening for alcohol.
The historical view was that glycolysis (involving the production of lactate) and aerobic metabolism were separate.
Work by Brooks around 2000 proposed new mechanisms of lactate metabolism.
Lactate (the product of glycolysis) is actually a substrate for aerobic metabolism.
Lactate can be moved around within the same cell and oxidised.
Components and processes include:
Sarcolemma
Glycogen
Glucose-6-Phosphate (G-6-P)
Lactate Transporter (LT)
Pyruvate
Glucose
Glycolysis (GL)
Tricarboxylic Acid cycle (TCA)
Carbon Dioxide (CO2)
Lactate Dehydrogenase (LDH)
Lactate can be moved to other cells and tissues to be oxidised.
Involves:
Type I and Type IIa muscle fibres
Monocarboxylate transporters (MCT1, MCT4)
Lactate acts as a potent signaling molecule in the body.
Lactate production increases as exercise intensity increases (rate of appearance (Ra)).
Lactate disappearance (Rd) does not increase to the same extent as the rate of appearance.
This leads to a net increase in blood (or muscle) lactate (Stanley et al., 1985).
Current evidence: O2 is available at the start of exercise.
But, there is an inability to utilise O2 in metabolic pathways and insufficient metabolic substrates at the start of exercise.
There is no oxygen deficit; La is produced as an integral part of aerobic metabolism.
Phosphocreatine resynthesis in muscle
Lactate removal
Elevated hormone levels
Elevated heart rate and breathing rate post-exercise
Elevated core body temperature
Restoration of O2 stores in muscle and blood
Correlation does not mean causation.
Force decreases as there is a decrease in intracellular pH.
But force recovers faster than the recovery in pH, suggesting a disconnect (Allen et al. 2008).
Lactate remains a useful measure to indicate the changes in metabolism with exercise.
Lactate is produced at rest.
The H+ produced as a result of lactic acid may not cause the reduction in pH (even if pH is a cause of fatigue).
Lactate may actually protect against acidosis (Robergs et al. 2004).
Lactate prevents pyruvate accumulation and supplies NAD(+) needed in phase 2 of glycolysis.
Lactate should not be seen as a glycolytic waste product nor as an acidifier.
Lactate; acidosis; and fatigue; are not equivalent in human physiology.
Determinants of exercise performance:
HR max
SV max
Capillary density
Q max
[Hb]; % SaO2
[Ca – Cv O2] max
VO2 max
Oxidative enzymes
% VO2max at LT
Running economy
Velocity at LT
Max velocity in distance running
The LT is worth measuring, even if we do not fully understand the mechanisms.
Start at 9 km/h or 60 W.
4 min per stage.
Increased intensity of 1 km/h or 20 W per stage.
30 s rest per stage to allow for blood sampling (treadmill only).
Lactate threshold is calculated from plotting intensity (speed, power) on the x-axis and blood lactate concentration on the y-axis.
A curve is fitted, and LT determined using an equation of choice.
MLSS = the highest blood La- and workload that can be obtained without continued blood lactate accumulation.
The blood La- concentration varies by < 1mmol/L during the last 20 mins of constant intensity exercise.
16 weeks of physical training in 8 male students.
There is a rightward shift in the blood lactate concentration curve.
Can work harder before starting to accumulate blood lactate.
Lactate is not a waste product and does not cause fatigue!
Lactate can be shuttled between and within cells – oxidised to produce ATP or converted to glycogen in the liver.
Produced from anaerobic metabolism but can be a substrate for aerobic metabolism.
Lactate can be an important performance measure.