Have you always thought that lactic acid is no good for the body? Think again. Investigators from UC Berkeley have shown that athletic training teaches the body to efficiently utilize lactic acid as a source of fuel in stressful situations:
In a paper in press for the American Journal of Physiology – Endocrinology and Metabolism, published online in January, Brooks and colleagues Takeshi Hashimoto and Rajaa Hussien in UC Berkeley’s Exercise Physiology Laboratory add one of the last puzzle pieces to the lactate story and also link for the first time two metabolic cycles – oxygen-based aerobic metabolism and oxygen-free anaerobic metabolism – previously thought distinct.
“This is a fundamental change in how people think about metabolism,” Brooks said. “This shows us how lactate is the link between oxidative and glycolytic, or anaerobic, metabolism.”
He and his UC Berkeley colleagues found that muscle cells use carbohydrates anaerobically for energy, producing lactate as a byproduct, but then burn the lactate with oxygen to create far more energy. The first process, called the glycolytic pathway, dominates during normal exertion, and the lactate seeps out of the muscle cells into the blood to be used elsewhere. During intense exercise, however, the second ramps up to oxidatively remove the rapidly accumulating lactate and create more energy.
Training helps people get rid of the lactic acid before it can build to the point where it causes muscle fatigue, and at the cellular level, Brooks said, training means growing the mitochondria in muscle cells. The mitochondria – often called the powerhouse of the cell – is where lactate is burned for energy…
Brooks always suspected, however, that the muscle cell itself could reuse lactate, and in experiments over the past 10 years he found evidence that lactate is burned inside the mitochondria, an interconnected network of tubes, like a plumbing system, that reaches throughout the cell cytoplasm.
In 1999, for example, he showed that endurance training reduces blood levels of lactate, even while cells continue to produce the same amount of lactate. This implied that, somehow, cells adapt during training to put out less waste product. He postulated an “intracellular lactate shuttle” that transports lactate from the cytoplasm, where lactate is produced, through the mitochondrial membrane into the interior of the mitochondria, where lactate is burned. In 2000, he showed that endurance training increased the number of lactate transporter molecules in mitochondria, evidently to speed uptake of lactate from the cytoplasm into the mitochondria for burning.
The new paper and a second paper to appear soon finally provide direct evidence for the hypothesized connection between the transporter molecules – the lactate shuttle – and the enzymes that burn lactate. In fact, the cellular mitochondrial network, or reticulum, has a complex of proteins that allow the uptake and oxidation, or burning, of lactic acid.
“This experiment is the clincher, proving that lactate is the link between glycolytic metabolism, which breaks down carbohydrates, and oxidative metabolism, which uses oxygen to break down various fuels,” Brooks said.
Post-doctoral researcher Takeshi Hashimoto and staff research associate Rajaa Hussien established this by labeling and showing colocalization of three critical pieces of the lactate pathway: the lactate transporter protein; the enzyme lactate dehydrogenase, which catalyzes the first step in the conversion of lactate into energy; and mitochondrial cytochrome oxidase, the protein complex where oxygen is used. Peering at skeletal muscle cells through a confocal microscope, the two scientists saw these proteins sitting together inside the mitochondria, attached to the mitochondrial membrane, proving that the “intracellular lactate shuttle” is directly connected to the enzymes in the mitochondria that burn lactate with oxygen.
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