Alanine is a nonessential amino acid. It is the second most abundant amino acid in circulation, after glutamine. It is found in many foods including eggs, meat, lentils, and fish. Alanine is involved in sugar metabolism for energy and is important in immune system function, specifically T lymphocyte activation. Interestingly, alanine is an agonist that binds to the glycine site of N-methyl-d-aspartate (NMDA) receptors in the brain and improves the positive and cognitive symptoms of patients with schizophrenia.
Alanine plays an important role in BCAA metabolism. BCAA are released from skeletal muscle during prolonged exercise. Their carbon backbones are used as fuel, while their nitrogen portion is used to form alanine. Alanine then gets converted to pyruvate and subsequently glucose in the liver using the glucose-alanine cycle (Cahill Cycle). This cycle is critical for regenerating glucose in prolonged fasting and is upregulated when glucagon, epinephrine, and cortisol are elevated.
It ultimately helps clear ammonia and provides glucose to energy-deprived muscle tissue.
The Cahill Cycle uses the enzyme alanine aminotransferase (ALT). ALT catalyzes the transfer of the amino group from alanine to an alpha keto acid (typically alpha-ketoglutarate), forming pyruvate and glutamate as byproducts. ALT is commonly measured on standard laboratory chemistry profiles to assess liver health.
References:
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- Ron-Harel N, Ghergurovich JM, Notarangelo G, et al. T Cell Activation Depends on Extracellular Alanine. Cell Rep. 2019;28(12):3011-3021.e3014.
- Hatano T, Ohnuma T, Sakai Y, et al. Plasma alanine levels increase in patients with schizophrenia as their clinical symptoms improve-Results from the Juntendo University Schizophrenia Projects (JUSP). Psychiatr Res. 2010;177(1- 2):27-31.
- Sarabhai T, Roden M. Hungry for your alanine: when liver depends on muscle proteolysis. The J Clin Investi. 2019;129(11):4563-4566.
- Garg U, Smith LD. Biomarkers Inborn Errors of Metabolism: Clinical Aspects and Laboratory Determination. Elsevier; 2017.
- Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Gen Metab. 2012;105(1):34-43.
- Habarou F, Brassier A, Rio M, et al. Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis. Mol Gen Met Rep. 2015;2:25-31.
- Brunette MG, Delvin E, Hazel B, Scriver CR. Thiamine- responsive lactice acidosis in a patient with deficient low-KM pyruvate carboxylase activity in liver. Pediatrics. 1972;50(5):702-711.
Alanine
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