Lecture on Lactate Metabolism

Introduction

• Lecturer: Professor Ben Bickman, Biomedical Scientist and Professor of Cell Biology
• Topic: Lactate metabolism
• Key Misconception: Humans do not have lactic acid; it’s lactate.

Basics of Lactate

• Lactate vs. Lactic Acid: Everything known about lactic acid is likely false. Lactate is present in humans, not lactic acid.
• Source of Lactate: Product of anaerobic (or non-oxidative/non-mitochondrial) glycolysis.
• Glycolysis Overview:
  • Glucose enters a cell and undergoes glycolysis, producing pyruvate.
  • Pyruvate can either:
    • Enter mitochondria (oxidative glycolysis) and become acetyl-CoA, leading to the Krebs cycle.
    • Stay outside mitochondria (non-oxidative glycolysis) and convert to lactate via lactate dehydrogenase.

Muscle and Red Blood Cells

• Muscle: A common source of lactate due to high energy demand during intense exercise.
• Red Blood Cells: Lack mitochondria, rely entirely on non-oxidative glycolysis, producing lactate.

Historical Perspectives

• Otto Meyerhoff: First to discover lactate as a product of glycolysis in muscle metabolism, won Nobel Prize in 1922.
• Cori Cycle:
  • Discovered by Carl and Gertie Cori.
  • Muscle produces lactate, which is converted to glucose in the liver and can be reused by muscles.
  • Highlights the recycling process of lactate to glucose.

Lactate as an Energy Source

• George Brooks: Proposed lactate shuttle theory.
  • Lactate is a viable energy source, not waste.
  • Can be utilized by mitochondria directly for energy.

Clinical Applications

• Traumatic Brain Injury (TBI): Lactate can bypass compromised glucose metabolism in the brain, providing an alternative fuel source.
• Fat Tissue Signaling:
  • Lactate can induce beiging of white adipose tissue, increasing metabolic rate.

Relevance to Disease

• Continuous Lactate Monitors:
  • Useful in athletics for training, but more importantly in medical diagnostics.
  • High lactate levels could indicate mitochondrial dysfunction or type 2 diabetes risk.
• Studies:
  • Elevated lactate levels are consistent with type 2 diabetes.
  • Lactate levels can predict metabolic risk.

Conclusion

• Lactate is a valuable molecule in energy metabolism and signaling.
• Far from being metabolic garbage or villain, it plays crucial roles in energy dynamics and disease prediction.
• Future potential in continuous monitoring for health diagnostics related to mitochondrial function and metabolic diseases.

Key Message: More knowledge leads to better health.

Lactate Metabolism: Dispelling Myths and Unveiling Its Significance

Introduction

• Professor Ben Bikman, a biomedical scientist and professor of Cell Biology, clarifies that humans have lactate, not lactic acid.
• Lactic acid's purported existence in the human body and its association with muscle soreness and fatigue are false.
• Lactate is a product of non-oxidative glycolysis (preferred term over anaerobic glycolysis).

Glycolysis and the Fate of Pyruvate

• During glycolysis, glucose is broken down into pyruvate.
• Pyruvate has two options:
  • Enter the mitochondria and undergo oxidative glycolysis, leading to the Krebs cycle and ATP production.
  • Stay outside the mitochondria and undergo non-oxidative glycolysis, where it's converted to lactate by lactate dehydrogenase.
• Tissues with high energy demands, like muscles, utilize non-oxidative glycolysis to produce ATP quickly, resulting in lactate production.
• Red blood cells, lacking mitochondria, rely entirely on non-oxidative glycolysis and are significant lactate producers.

History of Lactate Research

• Otto Meyerhof:
  • Discovered lactate's link to intense exercise and oxygen availability in muscle tissue.
  • Identified lactate as a product of non-oxidative glycolysis (Meyerhof cycle).
  • Received the Nobel Prize in 1922.
• Carl and Gertie Cori:
  • Discovered the Cori cycle, where lactate from working muscles is transported to the liver, converted back to glucose (gluconeogenesis), and released back into circulation for muscle use.
  • This cycle demonstrates lactate's role in energy recycling.
  • Gertie Cori was the first woman to win the Nobel Prize in Physiology or Medicine.
• George Brooks:
  • Proposed the lactate shuttle theory, demonstrating lactate as a viable fuel source.
  • Showed that mitochondria can uptake lactate, convert it to acetyl-CoA, and use it for energy production.

Lactate's Role in Traumatic Brain Injury

• After traumatic brain injury (TBI), glucose metabolism in the brain is often compromised.
• Lactate can serve as an alternative energy source, bypassing the impaired glucose metabolism.
• Studies show that lactate infusion can reduce brain swelling and improve intracranial pressure in TBI patients.
• Animal studies suggest lactate administration can prevent secondary brain damage post-TBI.

Lactate as a Signaling Molecule in Fat Tissue

• Lactate can signal fat cells to undergo "beiging" – becoming more like brown adipose tissue, which has a higher metabolic rate and burns energy for heat production.
• Lactate stimulates mitochondrial uncoupling in fat cells, promoting energy expenditure as heat, potentially aiding in fat mass management.

Clinical Relevance of Lactate Monitoring

• Continuous lactate monitors (CLMs) are becoming available. While their application in athletics is apparent (lactate threshold training), their potential extends further.
• Chronically high lactate levels in a non-exercising state could indicate mitochondrial dysfunction.
• Studies show a link between elevated lactate levels and:
  • Type 2 diabetes risk (Ishitoi et al., 2019).
  • Higher risk in non-diabetic relatives of type 2 diabetes patients (Sandqvist et al., 2001).
  • Development of type 2 diabetes (Atherosclerosis Risk in Communities study).
  • Reduced oxidative capacity, implying mitochondrial involvement.
• CLMs could offer early detection of mitochondrial problems and predict metabolic risks, including insulin resistance and type 2 diabetes.

Conclusion

• Lactate's reputation has shifted from a metabolic waste product to a valuable energy source and signaling molecule.
• Lactate plays crucial roles in energy recycling, fuel provision in various tissues (including the brain during TBI), and fat metabolism regulation.
• Continuous lactate monitoring holds promise for athletic training and, more importantly, early detection of metabolic issues and disease risks.