Alanine cycle

Liver takes carbon and nitrogen waste from muscle (alanine), disposes of the nitrogen, and recycles the carbon into glucose. 

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). 

Cooperation between liver and muscle allows muscle to get rid of nitrogen waste and recycle the carbon skeleton into glucose. 

The result is that the amino groups can be dumped out as alanine (the transamination product of pyruvate). In the liver and kidney, alanine is transaminated to yield pyruvate and glutamate. As in the Cord cycle, the pyruvate is converted to glucose by the liver and is shipped out. The glutamate is fed into the urea cycle-nitrogen disposal system to get rid of the excess nitrogen. 

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Major amino acids emanating from muscle are alanine (destined mainly for gluconeogenesis in liver and forming part of the glucose-alanine cycle) and glutamine (destined mainly for the gut and kidneys). 

Glycogenolysis and glycogen synthesis P-oxidation of fatty acids transamination and deamination of amino acids Cori cycle and glucose-alanine cycle, which recycles substrates between muscle and liver. 

Muscle protein catabolism generates amino acids some of which may be oxidized within the muscle. Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver. Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose the glucose is exported to tissues via the blood. This is the glucose-alanine cycle (Figure 7.11). In effect, muscle protein is sacrificed in order to maintain blood adequate glucose concentrations to sustain metabolism of red cells and the central nervous system. 

There is also a corresponding circulation system for the amino acid alanine. The alanine cycle in the liver not only provides alanine as a precursor for gluconeogenesis, but also transports to the liver the amino nitrogen arising in muscles during protein degradation. In the liver, it is incorporated into urea for excretion. 

The skeletal muscle is the most important site for degradation of the branched-chain amino acids (Val, Leu, lie see p. 414), but other amino acids are also broken down in the muscles. Alanine and glutamine are resynthesized from the components and released into the blood. They transport the nitrogen that arises during amino acid breakdown to the liver (alanine cycle see above) and to the kidneys (see p. 328). 

In muscle, transamination of pyruvate forms alanine, which is transported to the liver, where the reaction is reversed (the alanine cycle). 

FIGURE 18-9 Glucose-alanine cycle. Alanine serves as a carrier of ammonia and of the carbon skeleton of pyruvate from skeletal muscle to liver. The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle. 

The pyruvate produced by deamination of alanine in the liver is converted to glucose, which is transported back to muscle as part of the glucose-alanine cycle. 

Grubinko, V.V. and Arsan, O.M. (1995). The role of glucose alanine cycle in the adaptation to ammonia in fish (In Russian). Doklady Natsionalnoy Akademii Nauk Ukrainy 1995 (1), 107-109. 

Glucocorticoids also increase the activity of transaminases (aminotransferases), especially in the skeletal muscle. Aminotransferases serve to transfer the amino groups from amino acids to be metabolized to a-keto acids, especially pyruvate. In the latter case, the alanine thus formed is transported from the muscle into the bloodstream and extracted from there by the liver. In the liver, alanine is converted to glucose, and glucose may then return to the muscle as it does in the Cori cycle (Figure 18.4). This is the alanine cycle, and more about this is discussed in Chapter 20. Branched-chain amino acids are the principal donors of nitrogen to pyruvate in the muscle and are thus important actors in the alanine cycle. 

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