Robert A. Aldrich

Porphyrin metabolism. IV. Molecular structure of acetamide derivatives affecting porphyrin metabolism

Summary Twenty compounds related to Sedormid have been tested for porphyria-producing activity, using the chick embryo as the experimental animal. The molecular structure eliciting this response has been identified as a dialkyl-substituted acetamide or acetamide derivative where one substituent is an allyl group and the other contains at least three carbon atoms, preferably in a branched chain. The possibility that these compounds may interfere with the function of vitamin B12 is considered.

Porphyrin metabolism V. The metabolism of purines in experimental porphyria

In order to assess the efficiency of purine catabolism in experimental porphyria, the ability of chick embryos to oxidize and excrete purines was tested by administering preformed adenine, guanine, and xanthine. Both normal and porphyric embryos were found to convert adenine, but not guanine or xanthine, to uric acid, with the porphyric embryos apparently catabolizing exogenous adenine even more efficiently than the controls. Furthermore, adenine supplementation reduced the porphyrin output and improved the growth of Sedormid-treated embryos. Although adenosine was somewhat less effective than adenine, its use with allylisopropylacetamide gave qualitatively similar results. Results of tracer studies using glycine-2-C14 support the hypothesis of impaired purine biosynthesis in experimental porphyria.

Sedormid-induced porphyria in the rat.

Summary Sedormid administered to rats by stomach tube has caused marked increases in urinary uroporphyrin, coproporphyria and porphobilinogen, and concurrent clinical changes of paralysis, lethargy and gastrointestinal dysfunction. These findings constitute a syndrome closely resembling human adult porphyria. The disorder thus produced resembles that recently reported in rabbits.

Effect of Sedormid on the Developing Chick Embryo.

Summary The inoculation of Sedormid into the yolk sacs or allantoic cavities of 8-day-old embryonated eggs results in the prompt appearance in their allantoic fluids of materials exhibiting red fluorescence in ultraviolet light. These fluorescent materials appear to accumulate progressively with time. The results of quantitative estimations suggest that coproporphyrin and uroporphyrin are responsible for this fluorescence. Treated embryos are smaller than the controls and exhibit red fluorescence of the kidneys, sternum, and long bones under ultraviolet light. Further interpretation of these data must await isolation and characterization of the fluorescent substances.

A radioisotope technic for determining allantoic fluid volume of embryonated eggs.

Summary A method for determining the allantoic fluid volume of embryonated eggs by dilution of RISA is described. Experimental porphyria in chick embryos results in a marked increase in allantoic fluid volume.