The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin
Open accessAbstract
Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.
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Sydow, K., Daiber, A., Oelze, M., Chen, Z., August, M., Wendt, M., Ullrich, V., Mülsch, A., Schulz, E., Keaney, J. F., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419267 · Cited by 300
Klyosov, A. A., Rashkovetsky, L. G., Tahir, M. K., & Keung, W.-M. (1996) · Biochemistry · doi:10.1021/bi9521093 · Cited by 200
Kozlov, A. V., Dietrich, B., & Nohl, H. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705323 · Cited by 69
Cited by
Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities
Chen, C.-H., Ferreira, J. C. B., Gross, E. R., & Mochly-Rosen, D. (2014) · Physiological Reviews · doi:10.1152/physrev.00017.2013 · Cited by 614
Aldehyde dehydrogenases in cellular responses to oxidative/electrophilicstress
Singh, S., Brocker, C., Koppaka, V., Chen, Y., Jackson, B. C., Matsumoto, A., Thompson, D. C., & Vasiliou, V. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.010 · Cited by 601
Refined Geographic Distribution of the Oriental ALDH2*504Lys (nee 487Lys) Variant
Li, H., Borinskaya, S., Yoshimura, K., Kal’ina, N., Marusin, A., Stepanov, V. A., Qin, Z., Khaliq, S., Lee, M., Yang, Y., et al. (2009) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2009.00517.x · Cited by 285
Li, H., Hemann, C., Abdelghany, T. M., El-Mahdy, M. A., & Zweier, J. L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.342378 · Cited by 132
Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications
Song, B.-J., Abdelmegeed, M. A., Yoo, S.-H., Kim, B.-J., Jo, S. A., Jo, I., & Moon, K.-H. (2011) · Journal of Proteomics · doi:10.1016/j.jprot.2011.05.013 · Cited by 73
Metadata
- Authors
- Li, Y.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-01-19
- Volume
- 116
- Issue
- 2
- Pages
- 506-511
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2160297178
- Cited by
- 167
- References
- 3
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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