topic 8 again lol

LACTIC ACID METABOLISM

• at physiological pH (~7.4), lactic acid exists almost entirely in its deprotonated (ionized) form: lactate⁻.

• Even during aerobic metabolism, tissues still produce some lactate.

• Why?

  • Lactate dehydrogenase (LDH) is always active.

  • Pyruvate may not always be immediately taken up by mitochondria (due to limited proximity or transport rate), so it gets converted to lactate.

• Not just muscle — other tissues make lactate too:

  • skin, liver, heart, renal *RBCs

• Lactate turnover refers to the rate at which lactate is produced and utilized by the body. It's a measure of how much lactate is entering and leaving the bloodstream and being used for other metabolic processes

• Lactate isn’t waste — it’s a valuable:

• “lactate shuttle” = lactate produced in myofibers with increased rates of glycolysis (with increased amounts of M-LDH) used as energy by nearby or remote cells with oxidative capacity

• This is the Lactate Shuttle Hypothesis (Brooks, 1985):

  • M-type LDH (muscle) favors pyruvate → lactate

  • H-type LDH (heart) favors lactate → pyruvate

• Lactate moves from high glycolytic (Type II) to oxidative (Type I) tissues to be used as fuel.

lactic exchange

**heart loves lactate

*within cytosol of same cell, [lactate] increases away from mitochondria, decrease in [lactate] close to mito

• sarcolemma lactate (MCT) transporter: small amounts of lactate able to diffuse across cell membrane, vast majority crosses by symport with H+ (facilitated diffusion). *different isoforms.

  • they move lactate and a proton simultaneously in the same direction

• Epinephrine = ↑BPM

“Infusion of epinephrine at rest sharply increases lactate released by muscle (↑ glycolysis, no effect on O₂/P)”

EXERCISE CONDITIONS

• As soon as muscle contractions begin, anaerobic glycolysis activates rapidly, leading to lactate production.

  • The muscle starts releasing more lactate than it's consuming, creating a net output.

  • Simultaneously, lactate consumption also rises (e.g., by heart, liver, oxidative fibers).

✅ Net release underestimates total lactate produced

• Some lactate is used within the same muscle or nearby tissues before entering the blood.

• So, the actual lactate production is higher than what you see in blood measurements.

✅ Initial lactate release depends on muscle mass

• The more active muscle mass, the more lactate produced.

• as exercise at same sub max intensity continues , lactate release from muscles level off, consumption increases → drop in blood lactate

✅ Rate of lactate consumption depends on availability

• The body clears lactate faster when there’s more available in blood.

• Uptake by heart, liver, kidneys, Type I fibers increases as lactate levels rise.

✅ “VO₂ ↑ linearly with exercise intensity, but lactate ↑ in a curvilinear fashion”

• Oxygen consumption (VO₂) increases steadily with exercise intensity.

• Lactate stays low at first, then rises sharply once a certain intensity is reached.

• This point is often called the “lactate threshold” or OBLA (onset of blood lactate accumulation).

  • In trained individuals, blood lactate begins to rise rapidly around 60% VO₂max.

  • In trained endurance athletes, around 85% VO₂max. (??)

**not truly a threshold bc been producing lactate all along

primary reason for sudden lactate rise because as intensity increases:

• Sympathetic activation (fight or flight response) releases catecholamines (epinephrine, norepinephrine) but not oxidative enzymes

  • These stimulate glycolysis (↑ glucose breakdown) in muscle

    • also decrease in splanchnic blood flow(↓ uptake by liver and kidneys)

• substrate crossover (more CHO utilization)

• MU recruitment patterns change

➕ Additional Points:

• Catecholamines stimulate glycolysis but not oxidative enzymes:

  • → More pyruvate is made than mitochondria can handle

  • → More lactate is formed

• Reduced splanchnic blood flow (to liver/kidneys):

  • ↓ lactate uptake by liver and kidneys → more remains in blood

• Substrate crossover:

  • As intensity rises, the body shifts from fat to carbohydrates (CHO) as the primary fuel → ↑ glycolysis → ↑ lactate

• Motor unit recruitment changes:

  • At higher intensities, more Type II (glycolytic) fibers are recruited → produce more lactate

Fiber Type Differences in Lactate Handling

• during exercise, lactate produced by FG (fast glycolytic) fibers can either diffuse directly, or via blood into SO fibers which take it up & oxidize it.

• concurrently, some FOG fibers can release lactate while other consume it

• FG fibers have greater capillarization than needed for oxidative capacity. may be more important for lactate removal than oxygen delivery

• LDH profile (M vs H) strong predictor of whether fiber will be net consumer or net producer

• similar relationship (consumer vs producer) with glycerol - phosphate shuttle capacity of fibers (affects cytosolic NAD+/NADH)

  • During glycolysis, glucose → pyruvate → produces NADH

  • To keep glycolysis going, cells need to regenerate NAD⁺ (this is what the glycerol phosphate shuttle does)

• If a muscle fiber has strong shuttle activity, it keeps the NAD⁺ / NADH ratio high in the cytosol → reduces the need to convert pyruvate into lactate

• ↑ NAD+/NADH = ↓ in conversion rate of pyruvate to lactate

following endurance training, blood [lactate] at any given absolute or relative workload is ↓

• with training OBLA occurs at greater exercise intensity (mainly due to blunted catecholamine response)

• initially attributed to ↓lactate production ( ↑ mito, ↓ M-LDH)

• later studies with radioisotope tracers, suggest production unchanged but lactate utilization ↑

**refers to conversion of lactate to pyruvate which can then

a. accumulate

b. be released from msucle

c. be converted to alanine (AA;kreb’s cycle)

d. be used to produce glycogen

e. be oxidized as fuel

• in situ studied (arterial - venous difference) show training does ↓ lactate production during contractions

Post-Exercise Lactate Metabolism:

• since 1928 known that blood (lactate) ↓ more quickly with active than passive recovery *due to ↑ of blood flow to removal centers & ↑ energy demand

is there more optimal recovery intensity?

• find that rate of blood lactate decline ↑ along with intensity up to critical point

• most effective intensity to ↓ blood lactate during recovery just less than lactate threshold (OBLA) *recovery intensity depends upon fitness (60-80% VO2max)

• ↑ amount of active muscle during recovery also increases rate of blood lactate removal (arms & legs)