2026-06-05 マックス・プランク研究所
＜関連情報＞
- https://www.mpg.de/26544785/a-molecular-change-may-have-helped-humans-balance-nutrition-and-detoxification
- https://www.science.org/doi/10.1126/sciadv.ady1666
現代人におけるNAT1活性の新規リン酸化部位による調節 Regulation of NAT1 activity in modern humans by a novel phosphorylation site
Luise Fast, Mikel Lana Alberro, Eva Rakava, Richard Ågren, […] , and Hugo Zeberg
Science Advances Published:5 Jun 2026
DOI:https://doi.org/10.1126/sciadv.ady1666
Abstract
N-acetyltransferase 1 (NAT1) is an enzyme that acetylates certain drugs and carcinogens and is involved in folate metabolism. Some NAT1 variants are associated with susceptibility to cancer and birth defects. We show that while nearly all present-day humans carry a valine residue at position 149 and a serine residue at position 214, some carry the ancestral amino acids isoleucine and alanine at these positions because of gene flow from Neanderthals. Neither substitution affects enzymatic activity. However, replacing the serine residue, a known phosphorylation site, with a phosphomimetic aspartate reduces NAT1 activity by ~60%. Phosphorylation at this site may allow NAT1 to be down-regulated during pregnancy to reduce birth defect risk, while maintaining high activity in adults for xenobiotic clearance. This regulatory site is a molecular feature that differs between modern humans and Neanderthals.
