Mallette, Exton, Park, and Felig et al. proposed it for the first time between 1969 and 1970 in the skeletal muscle.
The Steps of the Glucose-Alanine Cycle
Purpose of the Glucose-Alanine Cycle
For example, aspartate transfers its amino group to glutamate when it reacts with oxaloacetate, forming α-ketoglutarate. Aspartate + Oxaloacetate ⇄ α-Ketoglutarate + Glutamate Some synthesized amino acids are used during metabolism, while others are used during glucose synthesis through gluconeogenesis.
In the Skeletal Muscles
The newly formed glutamate can be converted to glutamine by the cytosolic enzyme glutamine synthetase for transport to the liver. Glutamate + NH4+ + ATP → Glutamine + ADP + Pi Alternatively, the glutamate transfers its amino group to pyruvate through the enzyme alanine aminotransferase (ALT), forming alanine and α-ketoglutarate. Glutamate + Pyruvate ⇄ Alanine + α-Ketoglutarate
In the Bloodstream
Alanine leaves the muscle cells and moves through the circulatory system to the liver. The rate at which alanine is formed through transamination of pyruvate and sent to circulation is proportional to the synthesis of pyruvate inside the cell.
In the Liver
Once inside the liver, a hepatic ALT catalyzes a transamination reaction, converting alanine to pyruvate. Alanine acts as an amino group donor and α -ketoglutarate as an alpha-keto acid acceptor. Alanine + α-Ketoglutarate ⇄ Glutamate + Pyruvate Meanwhile, glutamate dehydrogenase in the mitochondrial matrix catabolizes glutamate into ammonium, which is then used in the urea cycle, and the α-ketoglutarate enters the Krebs cycle. It is an anaplerotic reaction linking amino acid metabolism with the Krebs cycle. Glutamate + H2O + NAD+ ⇄ α-Ketoglutarate + NH4+ + NADH + H+ The pyruvate can have different metabolic fates. It can be oxidized for ATP synthesis, leaving the glucose-alanine cycle, or can enter the gluconeogenesis pathway to produce glucose, which helps to continue the cycle. In an alternate reaction, glutamate can also react with oxaloacetate to form aspartate and alpha-ketoglutarate, catalyzed by aspartate aminotransferase. Glutamate + Oxaloacetate ⇄ Aspartate + α-Ketoglutarate The glucose-alanine cycle is less productive than the Cori cycle in energy production as the byproduct urea formed during the energy production from alanine requires removal from the system. This urea removal is an energy-dependent process requiring 3ATP to be hydrolyzed to 2ADP and 1AMP. However, unlike the Cori cycle, the NADH is stored for use in the electron transport chain. During intense exercise, our muscles produce lactate as a byproduct of anaerobic metabolism. Accumulation of lactate leads to muscle fatigue. The glucose-alanine cycle aids in removing lactate from the muscles by transporting it to the liver, where it is converted back into glucose.
