Alanine

Optimal Result: 77.9 - 1337 umol/g Cr.

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:

- Gropper S SJ, Groff J. Adv Nutr Human Metab. 5th ed. Belmont, CA: Wadsworth, Cengage Learning; 2009.

- Park YK, Linkswiler H. Effect of vitamin B6 depletion in adult man on the plasma concentration and the urinary excretion of free amino acids. JNutr. 1971;101(2):185-191.

- Vannucchi H, Moreno FS, Amarante AR, de Oliveira JE, Marchini JS. Plasma amino acid patterns in alcoholic pellagra patients. Alcohol Alcoholism. 1991;26(4):431-436.

- 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.

What does it mean if your Alanine result is too low?

May point to hypoglycemic conditions because of its role in gluconeogenesis. Supplement with alanine and the branched chain amino acids leucine, isoleucine and valine.

Low protein intake, low BCAA levels, gastrointestinal malabsorption and maldigestion, or increased demands in gluconeogenesis, may result in lower alanine levels.

There is some literature to suggest that vitamin B6 and vitamin B3 normalized plasma alanine levels.

Because of its role in the CNS, lower plasma alanine levels have been seen in schizophrenic patients and an increase in plasma alanine correlated with symptom improvement.

What does it mean if your Alanine result is too high?

Possible inadequate cellular energy substrates. Check for hypoglycemia or for exercise prior to blood draw. Chronic use of alanine for energy can lead to muscle wasting. Supplement the branched-chain amino acids.

High protein intake of alanine-rich foods can elevate levels. Because of the relationship between alanine and the clearance of ammonia and nitrogen, it may be elevated in urea cycle disorders to serve as a reservoir for waste nitrogen.

Biotin, thiamine, other nutrients are cofactors within the pathways of alanine metabolism. Functional need for these nutrients may elevate alanine levels.

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