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β-Hydroxy[14C]biotin and two 14C-methyl ketones have been isolated and identified for the first time from culture filtrates of a pseudomonad grown on [14C]biotin. The methyl ketones arise from decarboxylation of the β-keto acids derived from biotin and bisnorbiotin. Also, β-hydroxy[14C]biotin sulfone was isolated from similar cultures which contained [carboxy-14C]biotin sulfone plus biotin for growth. These results confirm that the valeric acid side chain of biotin is degraded via β oxidation which can proceed only in part with the rather metabolically inactive sulfone. Biotin d-sulfoxide isolated from a culture filtrate of the pseudomonad grown on [carboxy-14C]biotin was found to have the same specific radioactivity as that of the biotin initially present. This provides strong evidence that the d-sulfoxide arises through natural oxidation of the thioether function of the vitamin. No radioactive, ring-degraded products could be detected following growth on [carboxy-14C]biotin, [carboxy-14C]biotin d-sulfoxide, [carboxy-14C]biotin 1-sulfoxide plus biotin, or [carboxy-14C]biotin sulfone plus biotin. Hence, it is increasingly certain that degradation of the side chain must precede cleavage of the bicyclic structure of this vitamin.

Evidence derived from physical, chemical, and kinetic studies of a partially purified branched chain α-keto acid dehydrogenase establishes that both α-ketoisocaproic and α-keto-β-methylvaleric acids are oxidatively decarboxylated by a single enzyme complex. This situation is consistent with the current clinical observations of branched chain ketoaciduria. The significance of this finding is discussed in relation to metabolic aspects of the disease.