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In addition to Cori Cycle, the lactate shuttle hypothesis proposes complementary functions of lactate in multiple tissues. Contrary to the long-held belief that lactate is formed as a result of oxygen-limited metabolism, substantial evidence exists that suggests lactate is formed under both aerobic and anaerobic conditions, as a result of substrate supply and equilibrium dynamics.
1.2 Recruited reaction steps of the citric acid cycle and malate aspartate shuttle 1.3 Reaction steps from malate to pyruvate and lactate 2 Intracellular compartmentalization of the glutaminolytic pathway
Cori cycle. The Cori cycle (also known as the lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori, [1] is a metabolic pathway in which lactate, produced by anaerobic glycolysis in muscles, is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate.
Anaerobic glycolysis is the transformation of glucose to lactate when limited amounts of oxygen (O 2) are available. [1] This occurs in health as in exercising and in disease as in sepsis and hemorrhagic shock. [1] providing energy for a period ranging from 10 seconds to 2 minutes.
The ammonia produced in neurons is fixed into α-ketoglutarate by the glutamate-dehydrogenase reaction to form glutamate, then transaminated by alanine aminotransferase into lactate-derived pyruvate to form alanine, which is exported to astrocytes. In the astrocytes, this process is then reversed, and lactate is transported in the other direction.
The research of Dalian Medical University [17] shows that there is a noticeable increase in the HCC patients’ citrate and malate levels, suggesting the possibility of higher activity of citrate–malate shuttle. This mechanism is effective when TCA cycle activity is low. The shuttle also helps the production of fatty acid and lactic acid.
The two main systems in humans are the glycerol phosphate shuttle and the malate-aspartate shuttle. The malate/a-ketoglutarate antiporter functions move electrons while the aspartate/glutamate antiporter moves amino groups. This allows the mitochondria to receive the substrates that it needs for its functionality in an efficient manner. [1]
One way to shuttle this reducing equivalent across the membrane is through the Glycerol-3-phosphate shuttle, which employs the two forms of GPDH: Cytosolic GPDH, or GPD1, is localized to the outer membrane of the mitochondria facing the cytosol, and catalyzes the reduction of dihydroxyacetone phosphate into glycerol-3-phosphate.