The action of aminobenzylthiazolium salts on thiamine destruction by the Chastek paralysis enzyme.

نویسندگان

  • R R SEALOCK
  • A H LIVERMORE
چکیده

The demonstration that certain thiamine analogues specifically and competitively inhibit the thiamine-destroying enzyme of fish tissues afforded an additional method for characterizing the action of the enzyme and analyzing the structural features of the inhibitor molecules in relation to their effectiveness. o-Aminobenzyl-(3)-bmethylthiazolium chloride at 5 X 10m4 M concentration was found to produce 100 per cent inhibition of the enzymatic destruction of 5 X 10m4 M thiamine (1). With the same concentration of the o-nitro compound corresponding to this amine no inhibition was encountered. The suggested importance of the amino group was further substantiated by the finding that /%aminoethyl-(3)-4methylthiazolium chloride at the above concentration caused 56 per cent inhibition, whereas its corresponding phthalimido derivative produced only 18 per cent inhibition. In the same study 6-aminopyrimidine compounds were likewise employed. Since they proved decidedly less effective in inhibitory activity, it was tentatively concluded that components other than the benzylamine moiety of the thiazolium compounds were of importance in the inhibition process. In any case, the application of the Lineweaver and Burk (2) treatment of the Michaelis and Menten (3) concept of enzyme action yielded an enzyme-inhibitor dissociation constant of 1.97 X lo+ mole per liter for the o-aminobenzylthiazolium salt. In the same experiment a Michaelis constant of 8.31 X 10m5 mole per liter was obtained for the enzyme-substrate (thiamine) complex. With this quantitative evidence of specific and competitive inhibitory activity, this analogue which so closely resembles the structural pattern of the vitamin was selected as the point of demarcation for the more detailed analysis of the essential characteristics of an inhibitor molecule. The task of selecting the points of alteration is greatly simplified with the

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عنوان ژورنال:
  • The Journal of biological chemistry

دوره 177 2  شماره 

صفحات  -

تاریخ انتشار 1949