George Brooks, Ph.D. on Lactate Shuttle Theory, Relevance for Traumatic Brain Injury & More

When pyruvate is infused intravenously, red blood cells and the lungs convert it to lactate within seconds to a minute in one circulatory passage.

"when you infuse it in one circulatory passage, it's all lactate. So the lungs do that, and red blood cells do that. The red blood cells and the lungs are loaded with enzymes to convert pyruvate to lactate. So even if you want to try to give pyruvate, within seconds or a minute, it's going to be lactate anyway" (said at 0:48:52)

Evidence supports that red blood cells and pulmonary tissue rapidly take up and convert circulating pyruvate to lactate due to high lactate dehydrogenase (LDH) activity and monocarboxylate transporter (MCT) expression. However, claiming that pyruvate is completely converted ("it's all lactate") in a single circulatory passage overstates the magnitude of first-pass pulmonary extraction. In vivo tracer studies in animal models demonstrate a transpulmonary pyruvate fractional extraction of approximately 43% per circulatory transit, rather than complete conversion, though rapid equilibration toward lactate continues across subsequent passages and within erythrocytes.

• partial: Transpulmonary pyruvate kinetics. (American journal of physiology. Regulatory, integrative and comparative physiology 2011) · cited 25x in the literature

  "Tracer-measured pyruvate fractional extraction averaged 42.8 ± 5.8% for all three conditions and was significantly higher during epinephrine stimulation (P < 0.05) than during either Con or LC conditions, that did not differ from each other... We conclude that a major site of circulating pyruvate extraction resides with the lungs and that during times of elevated circulating lactate, pyruvate, or epinephrine stimulation, pyruvate extraction is increased." (abstract, results, passage verified)

  pubmedfull study (doi)
• supports: Transpulmonary lactate shuttle. (American journal of physiology. Regulatory, integrative and comparative physiology 2012) · cited 31x in the literature

  "Tracer measured lactate fractional extractions were similar for control, 16.6% (SD 15.3), and lactate clamp, 8.2% (SD 15.3) conditions, but negative during Epi stimulation, -25.3% (SD 45.5) when there occurred a transpulmonary production, the conversion of mixed central venous pyruvate to arterial lactate." (abstract, results, passage verified)

  pubmedfull study (doi)