Pyruvate glucose-alanine cycle

Most tissues transfer the amino acid nitrogen to the liver to dispose of as urea. They, therefore, produce either alanine (from the pyruvate-glucose-alanine cycle, in skeletal muscle, kidney, and intestinal mucosa) or glutamine (skeletal muscle, lungs, neural tissues) or serine (kidney), which are released into the blood and taken up by the 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. 

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. 

The glucose-alanine cycle. Active muscle functions anaerobically and synthesizes alanine by a transamination reaction between glutamate and pyruvate, The alanine is transported to the liver, where the... 

Alternatively, in skeletal muscle, pyruvate can be transaminated to alanine (which affords a route for nitrogen transport from muscle to liver) in the liver alanine is used to regenerate pyruvate, which can then be diverted into gluconeogenesis. This process is referred to as the glucose-alanine cycle. 

The glucose-alanine cycle between the liver and the musculature is particularly significant. In muscle tissue, ammonia is generated during the degradation of amino acids (particularly the branched-chain amino acids). The transfer of ammonia to pyruvate yields alanine, which is then transported through the bloodstream to... 

Figure 23.16 PATHWAY INTEGRATION The glucose—alanine cycle. During prolonged exercise and fasting, muscle uses branched-chain amino adds as fuel. The nitrogen removed is transferred (through glutamate) to alanine, which is released into the bloodstream. In the liver, alanine is taken up and converted into pyruvate for the subsequent synthesis of glucose.

Alanine is formed from pyruvate in muscle. After it is transported to the liver, alanine is reconverted to pyruvate by alanine transaminase. Eventually pyruvate is used in the synthesis of new glucose. Because muscle cannot synthesize urea from amino nitrogen, the glucose-alanine cycle is used to transfer amino nitrogen to the liver. 

Gluconeogenesis citric acid cycle intermediates Glucose-alanine cycle glucose----> pyruvate -... 

Glucose, produced by the liver, is used for energy by the brain and other glucose-dependent tissues, such as erythrocytes. The muscle, under conditions of exercise, when the AMP-activated protein kinase is active, also oxidizes some of this glucose to pyruvate, which is used for the carbon skeleton of alanine (the glucose-alanine cycle see Chapter 38). 

Therefore one speaks of a glucose alanine cycle involving the conversion of alanine to pyruvate through the catalytic action of the proper transaminase. If starvation is prolonged, the alanine production in muscle is reduced and gluconeogenesis decreases in spite of the fact that the activities of the liver enzyme remain adequate. 

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. 

Figure 21.1 Metabolite and fuel movements in the fed state (high insulin/glucagon). Arrows indicate net movement of metabolites. There is a net synthesis of glycogen and fat in the liver. Glucose is converted to pyruvate and lactate during muscular activity. Both the Cori and alanine cycles are shown.

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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