Why we stop synthesizing essential amino acids: The Extracellular Protein Hypothesis

Abstract

Humans cannot synthesize nine of the twenty amino acids that constitute proteins, known as essential amino acids. It has been traditionally considered that this inability arose because humans could obtain these amino acids in sufficient quantities through their diet. However, recent advances in life sciences have shown that all eukaryotic organisms with the ability to ingest external protein resources have uniformly lost the ability to synthesize almost identical amino acids, including those belonging to branches of the evolutionary tree entirely different from humans, such as Dictyostelium and Tetrahymena. Yet, the reasons behind their essentiality and the commonality of these essential amino acids remain elusive and unexplained. In this paper, I propose a novel and simple explanation that organisms can maintain their amino acid balance by solely synthesizing amino acids that are more abundant in extracellular proteins compared to intracellular proteins. This explanation is based on two previously unrecognized assumptions. The first assumption is that intracellular proteins act as amino acid buffers for subsequent protein synthesis, facilitated by the continuous recycling of their amino acids during the degradation and synthesis cycle. The second assumption is that there are consistent differences in amino acid composition between extracellular and intracellular proteins, economically driven by the lower synthesis costs for extracellular structures. Despite the limited data available for examining these assumptions, the evidence lends support to their validity. Therefore, this "Extracellular Protein Hypothesis" provides a novel and convincing explanation to the nearly century-old mystery: the origin of essential amino acids.