April 12, 2023
Keio University School of Medicine
A research group led by Junpei Sasabe, a senior lecturer, Yusuke Gonda, a joint researcher (at the time of the study; currently an assistant at Juntendo University Hospital, Juntendo University School of Medicine), and Professor Masato Yasui of the Department of Pharmacology, Keio University School of Medicine, in collaboration with Professor Kenji Hamase of the Faculty of Pharmaceutical Sciences at Kyushu University and Professor Toshiaki Shimizu of the Department of Pediatrics at Juntendo University, has revealed that mammals maintain their internal environment by competing with symbiotic bacteria to preserve the balance of left- and right-handed amino acids.
Molecules used by life have a "handedness." Just as a right-handed glove can only be used by a right hand, the handedness of a molecule is crucial as it is directly linked to its function. Amino acids are a general term for compounds with an amino group (-NH2) and a carboxyl group (-COOH), and depending on their configuration, they exist as left-handed forms (L-amino acids) and their mirror images, right-handed forms (D-amino acids). However, life exclusively uses the left-handed form as the building blocks for proteins, thereby creating functional proteins that fit precisely like a hand in a glove, enabling smooth biological activities. For this reason, it is known that the amino acids in our bodies are predominantly left-handed, and creating a left-handed amino acid environment has been considered a "hallmark of life."
On the other hand, recent advances in analytical technology have revealed that mammals, including humans, also contain a mixture of right-handed D-amino acids, which have different functions from their left-handed counterparts. Furthermore, it has become clear that an imbalance in the left-right ratio of amino acids can cause abnormalities in neural, metabolic, and immune functions. So, what causes this imbalance in the body's amino acids, and how is it maintained? In this study, by separating the left- and right-handed forms and comprehensively quantifying amino acids, we have clarified that the previously mysterious imbalance of amino acids in the body is primarily caused by symbiotic bacteria converting left-handed forms into right-handed ones. In response, we found that mammals maintain their internal left-handed amino acid environment by selectively breaking down the right-handed amino acids produced by these symbiotic bacteria in the kidneys. This research is expected to contribute to understanding the symbiotic relationship between mammals and bacteria mediated by amino acids, as well as to the understanding of the mechanisms and the development of therapeutic targets for various immune, metabolic, and neurological diseases caused by disruptions in symbiotic bacteria. The results of this research were published in the American scientific journal The Proceedings of the National Academy of Sciences (PNAS) on April 3, 2023 (US Eastern Time).
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