Interaction of N-substituted ethanolamine analogs with ethanolamine ammonia-lyase, an adenosylcobalamin-requiring enzyme.

A number of N-substituted ethanolamine derivatives have been found to interact productively with ethanolamine ammonia-lyase, an adenosylcobalamin (AdoCbl) requiring enzyme that catalyzes the conversion of vicinal amino alcohols to oxo compounds. Inhibition, inactivation, cleavage of AdoCbl, and exchange of tritium out of [5'-3H]AdoCbl were all observed, the effects varying from analog to analog. The most striking effects were seen with azetidin-2-ol and pyrrolidin-3-ol, two aliphatic heterocycles composed of ethanolamine in which the nitrogen is tied back to the carbinol carbon by methylene bridges containing one and two carbon atoms, respectively. Incubation of azetidinol with the enzyme.AdoCbl complex resulted in extensive inactivation of the enzyme accompanied by cleavage of the cofactor; exchange of 3H from [5'-3H]AdoCbl into a nonbasic compound was also seen. Pyrrolidinol interacted with the enzyme.AdoCbl complex in a substrate-like way, causing exchange of 3H from labeled cofactor into a basic compound (perhaps the pyrrolidinol itself) together with a slight amount of C-Co bond cleavage. The interaction of the enzyme.AdoCbl complex with pyrrolidinol suggests that productively bound substrate is associated with the active site in such a way that the dihedral angle between the nitrogen and the oxygen is about 120 degrees, a configuration which maximizes bond-bond repulsions between the substituents on the adjacent carbon atoms.