Comparative inhibition of bacterial and microsomal 3-ketodihydrosphingosine synthetases by L-cycloserine and other inhibitors.
Eleven compounds were examined for their capacity to inhibit the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthetase. Of these, L-cycloserine was the most potent, affecting both bacterial and brain microsomal enzymes to a significant degree at 0.04 mM. D- and L-cycloserine irreversibly inactivated the enzyme, indicating a suicide substrate mode of action. L-Cycloserine was a more potent inhibitor of the growth of Bacteroides levii than was D-cycloserine, indicating that inhibition of sphingolipid synthesis could be a factor in the growth inhibition.
D000818:Animals; D001439:Bacteroides / Q000201:enzymology*; D001921:Brain / Q000201:enzymology; D003523:Cycloserine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D003523:Cycloserine; C021473:3-ketodihydrosphingosine synthetase; D007652:Oxo-Acid-Lyases