The identity of xanthine oxidase and the Schardinger enzyme

SCHARDINGER 1902 observed that methylene blue was reduced by formaldehyde in the presence of fresh milk.The enzyme concerned in the oxidation of this and other aldehydes became known as "Schardinger's enzyme".Hopkins 1921 found that certain extracts of yeast and of animal tissues also reduced methylene blue when added to milk.Morgan et al. 1922 identified the reducing substance as hypoxanthine and showed that its oxidation was effected by a system similar to that present in tissues.These authors first established that " xanthine oxidase " had many properties in common with the Schardinger enzyme.They found that tissues which were capable of oxidising purines would in all cases also oxidise aldehyde.This striking parallel occurrence of xanthine oxidase and the Schardinger enzyme in milk and in tissues raised the question of their identity.These authors concluded that identity was im- probable, because (a) the extreme specificity of enzymes towards their substrates argues in general against one and the same enzyme activating substances so different as purines and aldehydes; (b) the optimum concentration of purine was only one-hundredth of the optimum concentration of aldehyde; (c) the relative activities of the two enzymes varied from one sample of milk to another.Dixon and Thurlow made a preparation of xanthine oxidase from milk 1924, 1 and studied the dynamics of the enzyme system 1924, 2.They discussed the following evidence for and against its identity with the Schardinger enzyme.(a) Uric acid inhibits both enzymes to a marked extent.The inhibition of an aldehyde oxidase by a purine speaks for identity.(b) The slight inhibition by fluoride and cyanide is identical for each enzyme.(c) The enzymes cannot be separated: whenever one is precipitated, adsorbed, extracted or destroyed so also is the other.(d) The pH-activity curves with purines and with aldehyde each show a sharp break at PH 9 which in all cases is due to destruction of enzyme.(e) There is a striking parallelism between the activities of the two enzymes in a large number of defatted preparations.The variations in relative activities observed by Morgan et al. were never great and could be explained by variations in the fat content of different samples of milk.(Dixon and Thurlow observed that fat accelerated the oxidation of hypoxanthine but not of aldehyde.)(f) The disparity in optimum concentrations of the two classes of substrate cannot be used as an argument against identity since several cases are known of one enzyme activating two substrates at very different optimum concentrations.These authors concluded that the balance of evidence was in favour of identity though it was not sufficient to justify a positive statement to that effect.Morgan 1926 studied the distribution of xanthine oxidase in tissues from many animal species.Wherever xanthine oxidase was found it was invariably ( 1732 ) 4 ,, 20 ,, 10 ,, 45 ,, 2-6 2.0 C.