Glucose-Alanine Cycle

Glucose-Alanine Cycle

Introduction:

• There is a continuous transport of amino acids from muscle to liver, which predominantly occurs during starvation.
• Alanine dominates among the transported amino acids.
• It is postulated that pyruvate in skeletal muscle undergoes transamination to produce alanine.
• Alanine is transported to the liver and used for gluconeogenesis.
• This cycle is referred to as glucose-alanine cycle.

Mechanism:

• Alanine also plays a special role in transporting amino groups to the liver in a nontoxic form, via a pathway called the 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.
• In muscle and certain other tissues that degrade amino acids for fuel, amino groups are collected in the form of glutamate by transamination.

• Glutamate can be converted to glutamine for transport to the liver, as given below:

• Or it can transfer its α-amino group to pyruvate, a readily available product of muscle glycolysis, by the action of alanine aminotransferase.
• The alanine so formed passes into the blood and travels to the liver.

• In the cytosol of hepatocytes, alanine aminotransferase transfers the amino group from alanine to α-ketoglutarate, forming pyruvate and glutamate.
• Glutamate can then enter mitochondria, where the glutamate dehydrogenase reaction releases, or can undergo transamination with oxaloacetate to form aspartate, another nitrogen donor in urea synthesis.
• The use of alanine to transport ammonia from skeletal muscles to the liver is another example of the intrinsic economy of living organisms.
• Vigorously contracting skeletal muscles operate anaerobically, producing pyruvate and lactate from glycolysis as well as ammonia from protein breakdown.
• These products must find their way to the liver, where pyruvate and lactate are incorporated into glucose, which is returned to the muscles, and ammonia is converted to urea for excretion.
• The glucose-alanine cycle, in concert with the Cori cycle, accomplishes this transaction.

• The energetic burden of gluconeogenesis is thus imposed on the liver rather than the muscle, and all available ATP in muscle is devoted to muscle contraction.

References:

• Lehninger, A., Nelson, D. and Cox, M., 2013. Principles Of Biochemistry. 6th ed. New York: W.H. Freeman.
• Satyanarayana, U., 2014. Biochemistry. Elsevier Health Sciences APAC.
• Champe, P., Harvey, R. and Ferrier, D., 2008. Biochemistry. Philadelphia, Pa.: Wolters Kluwer / Lippincott Williams & Wilkins.
• Murray, R., Bender, D., Botham, K., Kennelly, P., Rodwell, V. and Weil, P., 2012. Harpers Illustrated Biochemistry. 29th ed. Blacklick: McGraw-Hill Publishing.