Biosynthesis of the Piperidine Nucleus The mode of incorporation of lysine into pipecolic acid and into piperidine alkaloids

6-3H,6-14C-DL-Lysine was administered in “metabolite overloading” experiments to the intact rat, to a lysine-less mutant of Neurospora crassa, to intact bean plants (Phaseolus vulgaris), and to excised shoots of Sedum acre. Pipecolic acid was then isolated from the tissues. In each case the pipecolic acid showed a 3H:14C ratio which was similar to that of the administered precursor. It follows that, in each case, the conversion of lysine into pipecolic acid proceeds via ε-amino-α-ketocaproic acid. α-Aminoadipic-δ-semialdehyde cannot be an intermediate. These results complement earlier findings that, in the rat, the nitrogen atom of pipecolic acid is supplied by the ϵ-amino group of lysine; they provide evidence for a similar route in N. crassa and in higher plants. They conflict with reports that, in higher plants, it is the α-amino group of lysine which supplies the nitrogen atom of pipecolic acid. In S. acre, the doubly labeled lysine was incorporated into sedamine without change in 3H:14C ratio.