Cori cycle cells

Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G., and Brown, M.S. (1994) Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates implications for the Cori cycle. Cell, 76. 865-873. 

Figure 6.10 The extended Cori cycle. Tumour cells convert glucose to lactate at a high rate and could be incorporated into this figure (Chapter 21).

Lactate is released into the blood by exercising skeletal muscle, and by cells that lack mitochondria, such as red blood cells. In the Cori cycle, blood-borne glucose is converted by exercising muscle to lac tate, which diffuses into the blood. This lactate is taken up by the liver and reconverted to glucose, which is released back into the circulation (Figure 10.2). 

Figure 18.4 The Cori cycle. Glucose is metabolized anaerobically to lactate, as in white muscle fibers or red blood cells. Lactate is exported into the bloodstream, extracted from there by the liver, and reconverted to glucose via gluconeogenesis. Glucose is then returned to the muscle.

The major metabolic product produced under normal circumstances by erythrocytes and by muscle cells during intense exercise is recycled through the liver in the Cori cycle. The metabolite is... 

Figure 5.9. The Cori cycle. Note that muscle and other tissues can produce excessive lactic acid in early cancer. Some lactate ionizes to H ion and thus lowers local pH. These acid effects are thought to disturb cell-to-cell interactions by ceUnlar water and pH imbalances with chromatin/DNA rearrangements and hence is proposed to initiate neoplastic environments according to the Warburg cancer theory. The Cori cycle repeats many times in advancing cancer and because of the net loss of energy by 2 ATP - 6 ATP = -4 ATPs per each Cori cycle, there is loss in the ability maintain tissne. Hence, there is a wasting of tissne over time. Cachexia is seen in a high percentage of terminal cancer patients.

Lactate is released by red blood cells and other cells that lack mitochondria or have low oxygen concentrations. In the Cori cycle, lactate is released by skeletal muscle during exercise (Figure 8.8). After lactate is transferred to the liver, it is reconverted to pyruvate by lactate dehydrogenase and then to glucose by gluconeogenesis. 

Lactate released from cells undergoing anaerobic glycolysis is taken up by other tissues (primarily the liver, heart, and skeletal muscle) and oxidized back to pyruvate. In the liver, the pymvate is used to synthesize glucose (gluconeogenesis), which is returned to the blood. The cycling of lactate and glucose between peripheral tissues and liver is called the Cori cycle (Fig. 22.10). 

Fig. 22.10. Cori cycle. Glucose, produced in the liver by gluconeogenesis, is converted by glycolysis in muscle, red blood cells, and many other cells, to lactate. Lactate returns to the liver and is reconverted to glucose by gluconeogenesis.

In terms of equilibrium, explain why lactate must be removed from muscle cells under anaerobic conditions and why lactate does not accumulate in the liver under these conditions. (Hint Think of the Cori cycle.)... 

Lactate is being produced continuously from glucose by anaerobic glycolysis in red blood cells, the retina and the kidney medulla. This lactate is recycled to glucose by a process known as the Cori cycle. The lactate is returned to the liver and is metabolised to glucose by gluconeogenesis in a process that consumes the equivalent... 

The result is that fiver metabolism effectively comes to a standstill. However, anaerobic metabolism elsewhere (e.g. by the red blood cells) continues to provide the fiver with lactic acid which cannot be disposed of as usual by the Cori cycle (Chapter 17). The consequence is lactic acidosis. 

Any excess lactate is taken up by the liver, converted into pyruvate and then into glucose. This, along with the production of lactate from glucose in muscle cells, constitutes the Cori cycle. 

Huang, DC., O Reilly, L.A., Strasser, A., and Cory, S., The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry, EMBO J., 16 (15), 4628, 1997. 

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