METHANOL METABOLISM IN THE RAT’ 292

The controversy as to which enzyme system is primarily responsible for the first step in the oxidation of methanol by mammals can be said to have originated with the isolation of crystal-line horse liver alcohol dehydrogenase by Bon-nichsen (1950). Until then it was widely be-lieved that alcohol dehydrogenase (ADH) mediated the oxidation of both ethanol and methanol as follows: RCH2OH + DPN ADH RCHO + DPNH + ll. Lutwak-Mann (1938), who performed the first extensive studies on ADH, did much to encourage this view when she showed that the partially purified enzyme, which required DPN as a co-factor, reacted with both ethanol and methanol. Ethanol was oxidized about 9 times more rapidly than methanol. It came somewhat as a surprise, then, that the pure enzyme in combination with DPN, oxidized ethanol and other aliphatic alcohols, but not methanol (Theorell and Bon-nichsen, 1951). This observation redirected at-tention to the peroxidative system of Keilin and Hartree (1936, 1945) which had been proposed earlier as a mechanism for the oxidation of al-cohols. More recently, it has been shown that when the substrate concentration is very high, ADH will oxidize methanol slowly (Kini and Cooper, 1961), which is not totally unexpected in view of the previous knowledge that ADH will Received for publication July 12, 1963