ENZYMES 281 



to require a biotin containing coenzyme. Vitamins containing para- 

 aminobenzoic acid, e.g., folic acid and the "citrovorum factor," seem to be 

 concerned with the transfer of formyl or formaldehydo groups in the 

 organism (Chap. 9). The family of B12 vitamins has an effect on the 

 metabolism of methyl groups (Chap. 9) and on the synthesis of desoxy- 

 ribonucleotides. 



Role of enzymes in tissue oxidation 



It has already been noted in the discussion of coenzymes and in Table 

 10-1 (section F) that a large group of enzymes is concerned with oxida- 

 tion-reduction reactions. There are three general groups of enzymes in 

 this class, the oxidases, peroxidases, and dehydrogenases. In the 1920's 

 there were two concepts concerned with the oxidation of substrates in the 

 organism. The advocates of the Warburg school contended that sub- 

 stances were oxidized because of activation of oxygen by iron. In model 

 experiments with iron-containing charcoal and enzyme preparations, it 

 was shown that the oxidation of substrate was accompanied by a reduction 

 of iron from the ferric to the ferrous state. 



However, Wieland and co-workers demonstrated that an organic sub- 

 stance in the reduced form could be oxidized in the presence of palladium 

 black. Palladium is known to have a strong affinity for hydrogen, and 

 the process was termed "dehydrogenation." The idea was advanced that 

 biological oxidations occurred more as a result of activation of hydrogen 

 than of oxygen. This view was greatly advanced by the work of Thun- 

 berg who demonstrated that the removal of hydrogen from succinate, for 

 example, could be accomplished in the absence of oxygen by methylene 

 blue and a specific enzyme. Methylene blue is a dye which is readily 

 reduced and is thereby decolorized: 



HOOC— CH0CH2— COOH + MB 



Succinic acid Methylene 



blue 



enzyme 



HOOC— CH=CH— COOH + MB-H^ 



Fumaric acid Leuco 



methylene 



blue 

 (colorless) 



Ih will be seen later that both principles apply to oxidation processes in 

 living organisms. 



Oxidases are enzymes which lead to oxidation of a substrate by molecu- 

 lar oxygen. Thus cytochrome c is converted from the ferrous to the 



