Origin of Essential Amino Acids: Extracellular Matrix Hypothesis

Abstract

Essential amino acids cannot be synthesized in the human body, and their origin has been explained that humans were able to obtain sufficient amounts of these amino acids through their diet. However, as the genomes of various organisms have been analyzed, it has been revealed that eukaryotic cellular organisms with the ability to ingest have uniformly lost the ability to synthesize almost the same amino acids. Then the explanation that the human diet is the origin of the amino acids can no longer hold valid. In order to explain this question, many possible aspects are postulated and examined for possible explanations. However, to date, no hypothesis has been proposed directly explaining the origin of the essential amino acids.

In a previous paper, I reported that the first principal component of the amino acid compositions of the daily food composition table separates essential and nonessential amino acids. Because all foods are body parts of eukaryotic cellular organisms, I speculated that there is a difference in how organisms use essential and nonessential amino acids in their bodies.

Examination of all the proteins in the human genome revealed that amino acids with high synthesis cost and a more significant number of synthesis steps accumulate in the transmembrane domains of membrane proteins. In contrast, low synthesis costs and fewer steps tend to distribute in the extracellular proteins like in the extracellular matrix. Therefore, I speculate that the statistical differences between the essential and nonessential amino acids in the food composition tables result from differences in amino acid usage between intracellular and extracellular proteins.

Organisms synthesize their proteins in the cytoplasm of their cells. Although some materials are supplied from outside the cell, most amino acids used in the synthesis must be degradation products of their intracellular proteins. Furthermore, since the cell needs to synthesize the transmembrane domain of membrane proteins, cells must contain a certain amount of highly hydrophobic and high-synthetic cost amino acids. On the other hand, cells must synthesize large amounts of extracellular proteins to maintain their living environment. Because using high-synthesis-cost amino acids for extracellular proteins could be disadvantageous, lower-synthesis-cost amino acids are likely to be used for extracellular purposes. Therefore the lower-cost amino acids could be insufficient in the balance because they leave the cell.

Organisms that acquired the ability to ingest during evolution got the chance to survive without synthesizing amino acids. However, in reality, although they could stop synthesizing high-synthesis-cost amino acids that they can retain in the cell, organisms could not stop synthesizing low-synthesis-cost amino acids that they often use outside the cell. Therefore, humans and many other organisms have lost the ability to synthesize almost the same essential amino acids and have maintained the ability to synthesize almost the same nonessential amino acids. I propose this as the extracellular matrix hypothesis.