It has already been mentioned that alanine released from muscle may be 'pyru-vate in disguise' - pyruvate onto which has been transferred an amino group from the breakdown of another amino acid. Pyruvate is a potential precursor for gluconeogenesis. Glucose thus formed may be released into the circulation, taken up by muscle and, through glycolysis, pyruvate formed. This pyruvate may be transaminated - and so on. This has been termed the glucose-alanine cycle. It is very closely related to the glucose-lactate cycle or Cori cycle, described in the 1920s by the Coris (Carl and Gertrude Cori, husband and wife, who shared the Nobel Prize for Medicine in 1948). These two cycles are illustrated in Fig. 6.20. The glucose-alanine cycle provides a clear link between glucose and amino acid metabolism and attracted a lot of attention when it was first proposed by Philip Felig and colleagues (Felig et al. 1970). But it needs close examination. What does it achieve for the body?
There needs to be a link between amino acid and glucose metabolism. The body's store of carbohydrate is relatively limited and, as has been stressed several times, certain tissues require a supply of glucose. Much of the metabolic regulation we have been considering seems directed at preserving and storing glucose when it is available. But many amino acids can, in principle, be converted to glucose, so that the body's protein reserves - particularly the bulk of skeletal muscle - could maintain glucose production for a considerable time. Thus, there needs to be a mechanism for transporting the necessary substrates to the liver (the main site of gluconeogenesis). But the glucose-alanine cycle as just outlined does not do this: it merely recycles pyruvate, derived from glucose. It is a means by which muscle glycogen (which cannot lead directly to glucose release from muscle) may lead to release of glucose into the circulation (i.e. from the liver). It also provides a way for the muscle to export amino-nitrogen,
liberated from those amino acids whose 2-oxo acids it has oxidised (e.g. the branched-chain amino acids). The nitrogen will eventually be excreted as urea, which is synthesised in the liver.
In order for the glucose-alanine cycle to function as a means of transporting amino acid carbon to the liver for gluconeogenesis, the 'carbon skeleton' of the alanine also needs to be formed from an amino acid, not from glucose. In fact there is not a lot of evidence that this occurs, although much effort has been devoted to attempting to demonstrate it. Glutamine may be a more likely carrier of such carbon (as discussed above, Section 18.104.22.168). Nevertheless, the cycle certainly operates, even if only as an alternative arm of the Cori cycle.
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