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A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors
Open accessAbstract
When an enzyme exhibits a high affinity for an inhibitor, the steady-state analysis of the mechanism is complicated by the non-linearity of normal dose–response plots or of reciprocal replots. It is shown here that dose–response measurements generate a linear plot of inhibitor concentration divided by degree of inhibition against velocity without inhibitor divided by velocity with inhibitor; the concentration of enzyme may be derived from the extrapolated intercept of such plots, and the mechanism of inhibition from replots of the variation of the slope with substrate concentration. The limiting cases where virtually all inhibitor molecules are bound or virtually all are free are described, together with the situation when a significant proportion of the substrate becomes bound. This type of analysis indicates that the inhibitors of oxidative phosphorylation, rutamycin and bongkrekic acid, are tightly bound to rat liver mitochondria.
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Cited by
Rational design of potent sialidase-based inhibitors of influenza virus replication
von Itzstein, M., Wu, W.-Y., Kok, G. B., Pegg, M. S., Dyason, J. C., Jin, B., Van Phan, T., Smythe, M. L., White, H. F., Oliver, S. W., et al. (1993) · Nature · doi:10.1038/363418a0 · Cited by 1,862
Mechanisms by which mitochondria transport calcium
Gunter, T. E., & Pfeiffer, D. R. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.258.5.c755 · Cited by 1,640
Kinetics of the inhibition of thrombin by hirudin
Stone, S. R., & Hofsteenge, J. (1986) · Biochemistry · doi:10.1021/bi00364a025 · Cited by 586
Characterization of human type I and type II IMP dehydrogenases.
Carr, S. F., Papp, E., Wu, J. C., & Natsumeda, Y. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74247-1 · Cited by 403
Anastasi, A., Brown, M. A., Kembhavi, A. A., Nicklin, M. J. H., Sayers, C. A., Sunter, D. C., & Barrett, A. J. (1983) · Biochemical Journal · doi:10.1042/bj2110129 · Cited by 314
Metadata
- Authors
- Henderson, P. J. F.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1972-04-01
- Volume
- 127
- Issue
- 2
- Pages
- 321-333
- ISSN
- 0306-3283 (ISSN-L)
- OpenAlex
- W2414435754
- Cited by
- 522
- References
- 0
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Henderson, P. J. F. (1972). A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors. Biochemical Journal. https://doi.org/10.1042/bj1270321
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