Are Non Essential Amino Acids really unessential?

Vetagro Journal Club, #5

Amino acids (AA) have traditionally been divided into essential and non-essential based on the capability of an organism to synthesize them ex novo. Nevertheless, this definition is partly untrue as some of the so-called “essential” AA (EAA) can be synthesized from precursors that are chemically and structurally similar. For example, methionine can be synthesized by the transamination of its ketoacid but also by demethylation of homocysteine and to this respect, the only truly essential AA might be threonine and lysine.

On the other side, according to a strictly metabolic definition, the true non-essential AA (NEAA) should be synthesized de novo from a non-amino acidic nitrogen and a carbon source: in this case only glutamic acid and serine would categorize as truly NEAA.

There are then some AA that can be synthesized by more complex pathways than the simple transamination of the respective ketoacid and these are called conditionally essential because there are consistent limitations to the extent and time when these AA can be synthesized.

It is mostly thought that AA requirements are dictated by protein accretion and development but in reality this only accounts for 10% of the total AA requirements. In fact, AA subtend the majority of the most important physiological reactions such as gene expression regulation among others. In particular, glutamine, glutamate, arginine, glycine and proline, which are all classified as NEAA, are implicated in a variety of metabolic functions like mTOR pathway for protein synthesis in skeletal muscle; nitric oxide synthesis, which is implicated in the anti-inflammatory response, cell signalling via cAMP or cGMP dependent kinases and many others. NEAA can also be precursor of other bioactive molecules such as carnosine, creatine, glutathione, polyamines, and neurotransmitters that are all essential regulators of cell growth and differentiation and tissue development.

To date, AA nutritional requirements across species have been established for EAA only but this classical discrimination is inherently showing weaknesses, as in specific physiological contexts the body’s needs for a particular AA can be increased beyond its capabilities to synthesize them. 

As recent evidence supports the need to establish NEAA requirements, we should carefully reconsider how we approach protein/amino acidic nutrition for livestock and humans alike as we might be underestimating the real needs especially for those categories that are more exposed to specific nutritional demands like mothers at pregnancy and lactation, premature children, professional athletes, and older adults. Frail groups of people in particular, who are chronically exposed to inadequate protein intake and a consequent AA unbalance, should be provided with supplements and food choices able to fulfill essential and non-essential requirements. 

Reeds, 2000. J. Nutr. 130(7):1835S–1840S. Dispensable and Indispensable Amino Acids for Humans (here)

Wu et al., 2013. Amino Acids. 44:11071113. Dietary requirements of “nutritionally non-essential amino acids” by animals and humans (here)

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