Diet-induced atherosclerosis in macaque monkeys was suppressed by anticalcifying agents without changing abnormal levels of blood cholesterol and lipoprotein. The agents included inhibitors of arterial calcium deposition (diphosphonates) and a calcium ion antagonist (lanthanum). The study suggests that regulation of calcium flux and extracellular deposition in arteries may offer new principles of treatment for cardiovascular disease.
Two mutants of Aspergillus nidulans, which exhibit a growth response to L-lysine, but not to L--amincadipic acid, accumulated L-pipecolic acid when grown in media containing growth-limiting concentrations of L-lysine. No accumulation occurred when these mutants were grown on optimal concentrations of L-lysine, nor was pipecolic acid accumulation observed with other types of lysine-requiring mutants of A. nidulans. L-Pipecolic acid accumulation, but not growth, was delayed by addition of o-aminobenzaldehyde to the medium. Catalytic hydrogenation of extracts of cells grown in the presence of o-aminobenzaldehyde gave DL-pipecolic acid, whereas catalytic hydrogenation of da-aminoadipic-S-semialdehyde after prolonged treatment with o-aminobenzaldehyde gave D-pipecolic acid. The findings are consistent with the accumulation of Lpiperideine^-carboxylic acid in the presence of o-aminobenzaldehyde. Studies with C14-and N "-labeled -aminoadipic acid and C14-lysine indicate that the carbon chain of -aminoadipic acid rather than that of lysine is the major precursor of pipecolic acid, and that the nitrogen atom of -aminoadipic acid becomes the nitrogen atom of pipecolic acid.The participation of -aminoadipic acid in lysine biosynthesis in certain yeasts and fungi is suggested by the observation that several mutant microorganisms are able to utilize either lysine or -aminoadipic acid for growth (Mitchell and Houlahan, 1948;Bergstrom and Rottenberg, 1950), and by tracer studies on such a mutant of Neurospora crassa, which showed that C1 ^aminoadipic acid was converted to C1 '-lysine without significant change in specific radioactivity (Windsor, 1951). Although there is evidence that certain microorganisms can convert a-aminoadipic acid to lysine, the enzymatic reactions involved are not yet understood. A number of plausible intermediates may be considered, including aketoe-aminocaproic acid ( '-piperideine-2-carboxylic acid), a-aminoadipic-ó-semialdehyde ( 1piperideine-6-car boxy lie acid), and pipecolic acid; the possibility that iV-acyl derivatives of these compounds and of lysine may be involved must also be considered.In the course of studies on the biosynthesis of * The authors acknowledge the generous support of the
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