N-sulphation of desipramine in the rat brain.
1. Amine N-sulphotransferase (NST) activity with desipramine (DMI) as substrate was assayed in vitro in various areas of the rat brain. Biosynthesis of 3'-phosphoadenosine-5'-phospho35sulphate (PAPS) from sodium 35sulphate and ATP was also measured by coupling it to the sulphation of minoxidil by minoxidil sulphotransferase (MST). 2. For the DMI-NST reaction, an apparent Km = 0.5 mM was obtained for DMI and two apparent Kms = 0.3 and 1.7 microM for PAPS, whereas in the PAPS-generating reactions, Km for sodium 35sulphate = 20 microM. 3. Both the enzyme activities were widely distributed in rat brain. The rate of NST activity was 2-3 orders of magnitude lower than that of PAPS generation. N-sulphoconjugation of DMI, which is proposed as a possible biotransformation pathway of DMI in the rat brain, could conceivably be supported adequately by the 'active sulphate' generated within the same areas of the brain.
Wong
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KO
Department of Biochemistry, National University of Singapore.
Wong
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KP
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D003891:Desipramine / Q000493:pharmacokinetics*; D004298:Dopamine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008914:Minoxidil / Q000493:pharmacokinetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014665:Vasodilator Agents / Q000493:pharmacokinetics
D000929:Antidepressive Agents, Tricyclic; D009419:Nerve Tissue Proteins; D009596:Nitrophenols; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014665:Vasodilator Agents; D010724:Phosphoadenosine Phosphosulfate; D008914:Minoxidil; C015802:2,6-dichloro-4-nitrophenol; D000255:Adenosine Triphosphate; D015238:Sulfotransferases; D003891:Desipramine; D004298:Dopamine; C024836:4-nitrophenol