The "Degradation Burden Hypothesis" for the Origin of Essential Amino Acids

While there are 11 non-essential amino acids (NEAAs) that are theoretically synthesized in vivo, the fundamental evolutionary and physiological background behind the division of the 20 standard amino acids into essential and non-essential categories remains elusive. Since the in vivo synthesis of NEAAs requires a nitrogen source, which is primarily derived from other amino acids, it is assumed that this synthesis relies on amino acid conversion. However, Greenstein (1957) reported that rats failed to grow adequately on a diet containing only the nine essential amino acids plus arginine, but exhibited normal growth when alanine was supplemented. This suggests that the conversion solely from essential amino acids is insufficient to meet the body's demands for NEAAs.Subsequent studies have revealed that complex α-keto acids derived from large molecules, such as branched-chain amino acids, are cytotoxic. Given this, it is reasonable to infer that cells avoid the unnecessary degradation of high-molecular-weight amino acids. Consequently, during periods without an external supply, the degradation of low-molecular-weight amino acids would be prioritized, resulting in a profound imbalance in amino acid consumption. Even with enhanced recycling efficiency, the organism would need to maintain the synthetic capacity for these highly consumed, low-molecular-weight amino acids. We hypothesize that these preferentially consumed amino acids essentially correspond to what we now classify as NEAAs. In this paper, we propose the "Degradation Burden Hypothesis" as a complementary mechanism for the origin of essential amino acids.