Metabolic Consequences of Affinity Labeling of Cystathionase and Alanine Aminotransferase by l‐Propargylglycine in vivo

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Abstract
A single intraperitoneal administration of l‐propargylglycine (5 μmol/mouse) to micc led to an extensive decrease in the hepatic cystathionase activity within an hour. This low level of the enzymic activity (lower than 4% of the normal level) was maintained for one day and accompanied by a considerable increase in urinary cxcrction ofcystathionine, glycinc and alanine. The renal cystathionase activity and the alanine aminotransferase activity of liver, kidney and brain were affected to a less extent. An increase in the urinary level of alaninc was attributed to the decrease in alanine aminotransferase activity in these tissues. This was confirmed by the observation that a similar rise in the urinary alanine level was induced by the administration of 3‐chloro‐l‐alanine, which inactivated alanine aminotransferase but not cystathionase. Activities of these two enzymes were restored to their original levels within 5 days. The concentration of cystathionine in liver, kidney and brain increased rapidly upon the administration of l‐propargylglycine. Glutathione in liver diminished in parallel with the increase in cystathionine. reaching 40% of the original level when the cystathionine level was at a inaxiinum. Following the restoration of the hepatic cystathionase activity, the cystathionine level declined gradually with concomitant increase in the glutathione level. These findings indicate that in liver the cystathionine pathway supplied more than a half of the cysteine store for the biosynthesis of glutathione. In contrast with the liver, this metabolic correlation between cystathionine and glutathione was not explicit in both the kidney and brain, suggesting that the supply of cysteine for the maintenance of glutathione in these tissues might be from a source other than the cystathioninc pathway.