Norvaline is an amino acid with the formula CH32CHCO2H. The compound is an isomer of the more common amino acidvaline. Like most other α-amino acids, norvaline is chiral. It is a white, water-soluble solid.
Occurrence
Norvaline is a non-proteinogenic unbranched-chain amino acid. It has previously been reported to be a natural component of an antifungal peptide of Bacillus subtilis. Norvaline and other modified unbranched chain amino acids have received attention because they appear to be incorporated in some recombinant proteins found in E. coli. Its biosynthesis has been examined. The incorporation of Nva into peptides reflects the imperfect selectivity of the associated aminoacyl-tRNA synthetase. In Miller–Urey experiments probing prebiotic synthesis of amino acids, norvaline, but also norleucine, are produced. Norvaline is known to promote tissue regeneration and muscle growth, and to become a precursor in the penicillin biosynthetic pathway. Norvaline has not been reported to be toxic at doses up to 5 grams a day, and it is commonly used by bodybuilders to increase muscle mass. At higher concentration, over 5 grams a day, norvaline was shown to decrease cell viability and caused necrotic cell death and significant changes to mitochondrial morphology and function. At high concentrations, all amino acids are cytotoxic, and norvaline toxicity could be attributed to protein amino acid mimicry. However, the conclusions of this study have been recently questioned, because the demonstrated l-norvaline toxicity is limited to specific in vitro assays at exceedingly high concentrations. Moreover, in higher organisms, l-norvaline is well tolerated, and in vivo toxicity is not apparent.
Nomenclature
Norvaline and norleucine both possess the nor- prefix for historical reason, despite current conventional usage of the prefix to denote a missing hydrocarbon group. The name is not systematic, and the IUPAC/IUB Joint Commission on Nomenclature recommends that this name should be abandoned and the systematic name should be used.
Norvaline is a promising candidate drug for the treatment of Alzheimer's disease. It is a non-competitive arginase inhibitor which readily crosses the blood-brain barrier, and reduces arginine loss in the brain. Amyloid-beta deposition is associated with L-arginine deprivation and neurodegeneration. Mice treated with Norvaline display improved spatial memory, increased neuroplasticity-related proteins, and decrease in amyloid-beta.
