Biosynthesis of a=Aminoketones and the Metabolism of Aminoacetone*

In 1956 Mauzerall and Granick (1) published a method for the calorimetric determination of a-aminoketones that depended on coupling of an a-aminoketone with acetylacetone to form a pyrrole with a free Q! position. The Ehrlich reagent, p-dimethylaminobenzaldehyde in acid, reacted at the CY position of this pyrrole to form a highly colored compound. This method made possible the determination of cY-aminoketones in the micromolar range. In the present study, chromatographic methods are described for the quantitative separation and determination of porphobilinogen, of a-aminoketones that lack a carboxylic group, e.g. aminoacetone, and of a-aminoketones that contain a carboxylic group, e.g. &aminolevulinic acid. With these methods, we have examined the abilities of mitochondria from normal guinea pigs to synthesize ar-aminoketones from several hydroxyamino acids, from several cy-keto acids with glycine, and from several acyl coenzyme A compounds with glycine. We have found that aminoacetone is formed readily by normal liver mitochondria, and we report especially on the synthesis and decomposition of this cr-aminoketone. Previous studies on cu-aminoketone formation were made with preparations from immature erythrocytes or from purple photosynthetic bacteria. The structure and biosynthesis of only a few a-aminoketones have been described. The first cw-aminoketone to be reported was &aminolevulinic acid, the precursor of the porphyrins. This compound was discovered by Shemin in 1953 (2). On the basis of labeling studies, Shemin concluded that &aminolevulinic acid was formed from succinyl coenzyme A and glycine. He suggested that analogous reactions might occur with other acyl coenzyme A compounds. Schulman and Richert (3) found later that pyridoxal phosphate was a coenzyme in &aminolevulinic acid synthesis. At present, the general reaction for synthesis of &aminolevulinic acid may be represented by Equation 1.