Why Is Tyrosine, More Abundant in Intracellular Proteins, Classified as a Non-Essential Amino Acid?: The Extracellular Demand Hypothesis

Abstract

In a previous report, I proposed the “Extracellular Protein Hypothesis,” which posits that a consistent disparity in amino acid usage between intracellular and extracellular proteins underlies the division of amino acids into essential and non-essential classes—based on the simple concept that organisms cannot dispense with the biosynthetic pathways for amino acids used abundantly in extracellular proteins. However, in that analysis, tyrosine appears not to follow this framework: despite statistical data suggesting its higher abundance in intracellular proteins, the biosynthetic pathway for tyrosine has been retained, and tyrosine is classified as a non-essential amino acid.

Tyrosine biosynthesis is maintained via its conversion from phenylalanine, yet there is a human disorder in which this conversion ability is almost entirely lost. In such cases, the body cannot produce sufficient amounts of neurotransmitters, hormones, and pigments without dedicated tyrosine supplementation. These clinical manifestations suggest that tyrosine biosynthesis may have been preserved primarily for synthesizing these non-protein molecules with specific functions—driven by both intercellular communication needs and environmental adaptation—both of which constitute demands from the extracellular environment. Building on these insights, I propose an “Extracellular Demand Hypothesis” in addition to (or potentially replacing) the previously proposed “Extracellular Protein Hypothesis.”