1. Effects of D-methionine in mice with noise-induced hearing loss mice
Yanru Wang, Yan Qu, Xuzhen Chen, Pu Zhang, Dan Su, Li Wang, Feifei Yang, Jiangdong Yang J Int Med Res. 2019 Aug;47(8):3874-3885. doi: 10.1177/0300060519860679. Epub 2019 Jul 21.
Objective: To study the effects of D-methionine in a mouse model of noise-induced hearing loss (NIHL). Methods: We investigated changes in auditory function and microscopic cochlear structure in a mouse model of NIHL, and carried out 4-hydroxynonenal (4-HNE) immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling, and examined expression levels of connexins 26 and 30 by western blot. Results: The auditory brainstem response threshold was significantly increased by noise exposure. Noise exposure also damaged the inner and particularly the outer hair cells in the cochlear basement membrane, while histochemistry demonstrated only scattered loss of hair cells in the basement membrane in mice treated with D-methionine before or after noise exposure. D-methionine inhibited apoptosis in the cochlear basement membrane, stria vascularis, and spiral ligament. 4-HNE expression in the basement membrane, stria vascularis, and spiral collateral ligament was increased by noise exposure, but this increase was attenuated by D-methionine. Connexin 26 and connexin 30 expression levels were reduced by noise exposure, and this effect was similarly attenuated by D-methionine administered either before or after noise exposure. Conclusion: D-methionine administered before or after noise exposure could rescue NIHL by protecting cochlear morphology, inhibiting apoptosis, and maintaining connexin 26 and 30 expression.
2. Biotransformation of D-methionine into L-methionine in the cascade of four enzymes
Z Findrik, D Vasić-Racki Biotechnol Bioeng. 2007 Dec 1;98(5):956-67. doi: 10.1002/bit.21501.
D-Methionine was converted to L-methionine in a reaction system where four enzymes were used. D-amino acid oxidase (D-AAO) from Arthrobacter protophormiae was used for the complete conversion of D-methionine to 2-oxo-4-methylthiobutyric acid. Catalase was added to prevent 2-oxo-4-methylthiobutyric acid decarboxylation. In the second reaction step, L-phenylalanine dehydrogenase (L-PheDH) from Rhodococcus sp. was used to convert 2- oxo-4-methylthiobutyric acid to L-methionine, and formate dehydrogenase (FDH) from Candida boidinii was added for NADH regeneration. Enzyme kinetics of all enzymes was analyzed in detail. Mathematical models for separate reactions steps, as well as for the complete system were developed and validated in the batch reactor experiments. Complete conversion of D-methionine to L-methionine was achieved. Considering that both enzymes act on different substrates, such a system could be easily employed for the synthesis of other amino acids from D-isomer, as well as from the racemate of a certain amino acid (DL-amino acid).
