Amino ketone formation and aminopropanol-dehydrogenase activity in rat-liver preparations

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Abstract
Rat tissue homogenates convert DL-1-aminopropan-2-ol into aminoacetone. Liver homo-genates have relatively high aminopropanol-dehydrogenase activity compared with kidney, heart, spleen and muscle preparations. Maximum activity of liver homogenates is exhibited at pH 9. 8. The Km for aminopropanol is approx. 15 m[image] calculated for a single enantiomorph, and the maximum activity is approx. 9m[mu]moles of aminoacetone formed/ mg. wet wt. of liver/hr. at 37[degree]. Aminoacetone is also formed from L-threonine, but less rapidly. An unidentified amino ketone is formed from DL-4-amino-3-hydroxybutyrate, the Km for which is approx. 200 m[image] at pH 9. 8. Aminopropanol-dehydrogenase activity in homo-genates is inhibited non-competitively by DL-3-hydroxybutyrate, the Ki being approx. 200 m[image]. EDTA and other chelating agents are weakly inhibitory, and whereas potassium chloride activates slightly at low concentrations, inhibition occurs at 50-100 m[image]. It is concluded that aminopropanol-dehydrogenase is located in mitochondria, and in contrast with L-threonine dehydrogenase can be readily solubilized from mitochondrial preparations by ultrasonic treatment. Soluble extracts of disintegrated mitochondria exhibit maximum aminopropanol-dehydrogenase activity at pH 9. 1. At this pH, Km values for the amino alcohol and NAD+ are approx. 200 and 1. 3 m[image] respectively. Under optimum conditions the maximum velocity is approx. 70m[mu] moles of aminoacetone formed/mg. of protein/hr. at 37[degree]. Chelating agents and thiol reagents appear to have little effect on enzyme activity, but potassium chloride inhibits at all concentrations tested up to 80 m[image]. DL-3-Hydroxybutyrate is only slightly inhibitory. Dehydrogenase activities for L-threonine and DL-4-amino-3-hydroxybutyrate appear to be distinct from that for aminopropanol. Intraperitoneal injection of aminopropanol into rats leads to excretion of aminoacetone in the urine. Aminoacetone excretion proportional to the amount of the amino alcohol administered, is complete within 24 hr., but represents less than 0. 1% of the dose given. The possible metabolic role of amino alcohol dehydrogenases is discussed.