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ELUCIDATION OF THE RATE-LIMITING STEP IN NOREPINEPHRINE BIOSYNTHESIS IN THE PERFUSED GUINEA-PIG HEART
Abstract
Guinea-pig hearts were perfused with varying concentrations of the norepinephrine precursors, tyrosine, 3,4-dihydroxyphenylalanine (dopa) and 3,4-dihydroxyphenethylamine (dopamine). With all three precursors the rate of norepinephrine synthesis increased as the concentration in the perfusion fluid increased. However, only with tyrosine were maximal rates achieved (0.2 µg/g/hr) at concentrations below 5 x 10 -4 M. The apparent Km for the overall reaction (tyrosine → norepinephrine) was found to be comparable to that observed for conversion of tyrosine to dopa by purified tyrosine hydroxylase ( 2 x 10 -5 M). These and other factors indicate that conversion of tyrosine to dopa is the rate-limiting step in the formation of norepinephrine in the sympathetic nervous system. Although ascorbic acid has been shown to be a requirement for purified dopamine-β-oxidase activity severe seurvy did not diminish the ability of isolated heart to form norepinephrine from tyrosine or dopamine.
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Citations
Cited by
The Dopamine Hypothesis of Schizophrenia: A Review*
Meltzer, H. Y., & Stahl, S. M. (1976) · Schizophrenia Bulletin · doi:10.1093/schbul/2.1.19 · Cited by 883
Ricaurte, G. A., Schuster, C. R., & Seiden, L. S. (1980) · Brain Research · doi:10.1016/0006-8993(80)90952-x · Cited by 490
Complex molecular regulation of tyrosine hydroxylase
Tekin, I., Roskoski, R., Carkaci-Salli, N., & Vrana, K. E. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1238-7 · Cited by 128
Ichinose, H., Ohye, T., Fujita, K., Pantucek, F., Lange, K., Riederer, P., & Nagatsu, T. (1994) · Journal of Neural Transmission - Parkinson's Disease and Dementia Section · doi:10.1007/bf02250926 · Cited by 107
Nakashima, A., Mori, K., Kaneko, Y. S., Hayashi, N., Nagatsu, T., & Ota, A. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.03.020 · Cited by 52
Metadata
- Authors
- Levitt, M., Spector, S., Sjoerdsma, A., & Udenfriend, S.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1965-04
- Volume
- 148
- Issue
- 1
- Pages
- 1-8
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2268197299
- Cited by
- 1,025
- References
- 0
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: ELUCIDATION OF THE RATE-LIMITING STEP IN NOREPINEPHRINE BIOSYNTHESIS IN THE PERFUSED GUINEA-PIG HEART. https://app.cochat.ai/papers/10.1016/s0022-3565(25)27006-9
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- Levitt, M., Spector, S., Sjoerdsma, A., & Udenfriend, S. (1965). ELUCIDATION OF THE RATE-LIMITING STEP IN NOREPINEPHRINE BIOSYNTHESIS IN THE PERFUSED GUINEA-PIG HEART. The Journal of Pharmacology and Experimental Therapeutics. https://doi.org/10.1016/s0022-3565(25)27006-9
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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