NeuroscienceAldose reductase, a key enzyme in the oxidative deamination of norepinephrine in rats
Section snippets
Chemicals
NE bitartrate, DHPG, DHMA, DHBA, and pargyline were all obtained from the Sigma Chemical Co. Matrex Gel Orange A was a product of the Amicon Corp. Prestained molecular weight protein standards for SDS–PAGE and peroxidase substrate (4-chloro-1-naphthol and hydrogen peroxide) were purchased from Bethesda Research Laboratories Life Technologies Inc. and Kirkegaard & Perry Laboratories, Inc., respectively. 3-Deoxy-3-fluoro-d-glucose was obtained from Omicron Biochemicals, Inc. The aldose reductase
DHPG formation by aldose reductase
The formation of DHPG from NE was investigated with an in vitro incubation system containing NE, MAO, and aldose reductase (Fig. 1 ). Incubation without MAO and aldose reductase resulted in peaks corresponding to unmetabolized NE and DHBA, an internal standard added to the reaction mixture after the incubation. When MAO was added to the mixture, the NE peak disappeared, indicating that MAO almost completely metabolized the amine. However, DHPG was not detected. The mixture containing NE and
Discussion
The major first step of intraneural metabolism of NE is oxidative deamination by MAO. This step terminates the physiological role of NE as a neurotransmitter and generates the potentially cytotoxic aldehyde intermediate DHMAL [24]. Since the major metabolite formed by this step is the reduction product, DHPG, rather than the oxidation product, DHMA, either aldose reductase or aldehyde reductase must play a major role in the removal of the potentially cytotoxic aldehyde intermediate. The present
Acknowledgements
The authors thank Dr. Simone Koenig and Dr. Henry M. Fales, Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, for ES-MS analysis
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