Nutritionally Nonessential Amino Acids: A Misnomer in Nutritional Sciences.

A mino acids (AAs) 3 are organic compounds that contain amino and acid groups (1). Based on the configuration of glyceraldehyde (Lor D-isomers as introduced by Emil Fischer in 1908), AAs (except for Gly, taurine, b-alanine, and g-aminobutyrate, which have no asymmetric carbon) exist as either Lor D-AAs. L-AAs are much more abundant than D-AAs in nature and are the physiologic isomers in animal and plant proteins. The AAs whose carbon skeletons are not synthesized de novo by animal cells were termed “nutritionally essential” AAs (EAAs) in 1912 and must be provided to animals to maintain their growth or nitrogen balance (2). In all animals, the EAAs consist of His, Ile, Leu, Lys, Met, Phe, Thr, Trp, and Val (3). In contrast, AAs whose carbon skeletons are synthesized de novo by animal cells were considered to be dispensable in diets and were classified as “nutritionally nonessential” AAs (NEAAs) (2). In most mammals (e.g., humans, rats, and pigs), the traditionally classified NEAAs are Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, Pro, Ser, and Tyr (3). The concepts of EAAs and NEAAs have been used for more than a century. Increasing evidence from studies in pigs, poultry, and fish has shown that animals do have dietary requirements of NEAAs to fulfill their genetic potential for maximum growth, reproduction, lactation, and production performance, as well as optimal health and wellbeing (4, 5). Rates of NEAA synthesis depend on the availability of EAAs and glucose, as well as species, breed, age, physiologic status, and disease state. The de novo synthesis of Arg in animal cells is species specific, with most mammals (e.g., humans, pigs, cattle, sheep, mice, and rats) synthesizing this AA from Glu, Gln, and Pro via the intestinalrenal axis. However, birds and some mammals (e.g., cats and ferrets) cannot synthesize Arg from Glu, Gln, or Pro in the enterocytes of the small intestine, which also may be true in most fish. In contrast to mammals, the synthesis of Pro from Arg in birds and certain fish is limited, and the synthesis of Pro from Glu and Gln is absent in birds and perhaps in most fish. The rate of Gly synthesis is much lower than the rate of Gly utilization in poultry and young pigs. In addition to proteinogenic NEAAs, the de novo synthesis of nonproteinogenic AAs should also be considered in nutrition. In cats, the conversion of cysteine into taurine is limited due to a low activity of cysteine dioxygenase and of cysteine-sulfinate decarboxylase, which catalyzes the formation of taurine from cysteine-sulfinic acid. Human infants, who have relatively low activities of both cysteine dioxygenase and cysteine-sulfinate decarboxylase compared with adults, require the dietary intake of taurine for maintaining normal retinal, cardiac, and skeletal functions. Pigs, ruminants, and poultry do not need dietary taurine for growth, milk production, or egg production. The supplementation of taurine to all plant–protein, taurine-free basal diets enhances growth and feed efficiency in carnivore fish (e.g., the rainbow trout and the Japanese flounder), but not the common carp, which suggests the suboptimal de novo synthesis of taurine by certain aquatic species (6). In nonruminants, the nutritionally important sources for the carbon skeletons of NEAAs consist of glucose and EAAs, whereas EAAs, but not ammonia, are nutritionally relevant sources of the a-amino group of NEAAs (1). In support of this view, the addition of safe amounts of ammonium chloride to the diets of nonruminants (e.g., rats, pigs, and poultry) does not result in the production of a nutritionally important quantity of any AA (7). Exogenous or endogenous ammonia is converted preferentially into urea in nonruminant mammals or into uric acid in birds (1). In the rumen of ruminants, a physiologic amount of ammonia is utilized by bacteria to form all AAs in the presence of adequate carbohydrates and sulfur; and the AAs are utilized by microbes for the synthesis of proteins, which are digested in the abomasum and small intestine. The pathways for ruminal ammonia assimilation are important in ruminants that consume lowquality feedstuffs (e.g., roughages and forages) and recycle urea through the saliva and blood circulation. Although ammonia is also converted into AAs by the bacteria in the large intestine, the nutritional importance of these reactions for AA syntheses is limited for animals (1). This is because the resulting AAs are primarily converted into microbial proteins in the hindgut, where proteins are not absorbed into the epithelial cells and are excreted in the feces. Although protein biosynthesis requires all proteinogenic AAs, NEAAs confer many functions that cannot be fulfilled by EAAs (1). These functions include the following: neurotransmission (Glu and Gly); the renal regulation of acid-base balance (Gln); the conjugation with bile acids (Gly and taurine); antioxidative reactions in retinal cells, heart, and skeletal muscle (taurine); the conversion of folate to tetrahydrofolate in one-carbon metabolism (Ser and Gly); syntheses of aminosugars (Gln), nucleotides (Asp, Gln, and Gly), glutathione (Glu, Gly, and Cys), heme Abbreviations used: AA, amino acid; AASA, amino acid that is synthesizable de novo in animal cells; EAA, nutritionally essential amino acid; mTOR, mechanistic target of rapamycin; NEAA, nutritionally nonessential amino acid.