The Cori Cycle

The localization of particular enzymes in only certain cells means that some organs depend on others for the complete metabolism of certain substrates. So far as carbohydrates are concerned, the 

---

Lactate produced by anaerobic metabolism in skeletal muscle passes to liver, which uses it to synthesize glucose, which can then return to muscle (the Cori cycle). 

Each mole of glucose that goes through the Cori cycle costs the liver 6 ATP equivalents. If the Cori cycle were perfect and there were an endless supply of ATP, liver could supply glucose equivalents forever just using the same carbon atoms (6 in as lactate, 6 out as glucose). However, some of the lactate (pyruvate) in the nonliver tissues is burned to C02 by the TCA cycle in die muscle and other tissues. It s this pool that must be replaced by fresh glucose from liver. 

The alanine cycle accomplishes the same thing as the Cori cycle, except with an add-on feature (Fig. 17-11). Under conditions under which muscle is degrading protein (fasting, starvation, exhaustion), muscle must get rid of excess carbon waste (lactate and pyruvate) but also nitrogen waste from the metabolism of amino acids. Muscle (and other tissues) removes amino groups from amino acids by transamination with a 2-keto acid such as pyruvate (oxaloacetate is the other common 2-keto acid). 

Lactic acid The normal concentration of lactate in the blood is about 1 mmol/L which is the balance between production and utilisation. Various tissues produce lactic acid and release it into the blood, from where it is taken up by liver and converted to glucose (or glycogen) (the Cori cycle, see above). 

Substrate cycling (e.g. the Cori cycle and the intra- and inter-cellular triacylglycerol/fatty acid cycles (Chapter 3)) in which there is no net metabolic change so that the energy from ATP hydrolysis is released as heat. 

After a period of intense muscular activity, the individual continues breathing heavily for some time, using much of the extra 02 for oxidative phosphorylation in the liver. The ATP produced is used for gluconeogenesis from lactate that has been carried in the blood from the muscles. The glucose thus formed returns to the muscles to replenish their glycogen, completing the Cori cycle (Fig. 23-18 see also Box 15-1). 

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). 

Carl F. Cori and Gerty T. Cori Physiology/Medicine Glycogen metabolism, the Cori cycle... 

Now let us consider the further conversion of PEP and of the triose phosphates to glucose 1-phosphate, the key intermediate in biosynthesis of other sugars and polysaccharides. The conversion of PEP to glucose 1-P represents a reversal of part of the glycolysis sequence. It is convenient to discuss this along with gluconeogenesis, the reversal of the complete glycolysis sequence from lactic acid. This is an essential part of the Cori cycle (Section F) in our own bodies, and the same process may be used to convert pyruvate derived from deamination of alanine or serine (Chapter 24) into carbohydrates. 

The cycling of lactate and glucose between muscle and liver in the Cori cycle. Under conditions of intense activity the muscle operates anaerobically so that the end product of glucose breakdown is lactate. This product can pass through the bloodstream to the liver and be converted to glucose, which can be returned to the muscle. 

C. lactate is converted back to glucose in the liver completing the Cori cycle. 

---