D. Graham, G. Thompson, M. Moore
Oct 1, 1979
Citations
1
Influential Citations
10
Citations
Quality indicators
Journal
Archives of biochemistry and biophysics
Abstract
Abstract The effects of four monopyrroles on porphyrin biosynthesis and excretion in the rat were studied. All four compounds investigated significantly increased total urinary porphyrin excretion and hepatic porphyrin levels while the effects on fecal excretion were equivocal. Peak porphyrin production elicited by treatment with ethyl 3-acetyl-2,4-dimethylpyrrole-5-carboxylate was found to be dose dependent, as was the time of maximum excretion. The effects of 3-ethyl-5-hydroxy-4,5-dimethyl-Δ 3 -pyrrolin-2-one, a compound excreted in abnormally high levels in the urine of patients with hepatic porphyria, were studied in greater depth. It was found that this compound caused an increase in the activity of δ-aminolevulinic acid synthase, in vivo , which was associated with a depression of microsomal levels of heme and cytochrome P -450. This depression of heme levels could not be related to increased catabolism or nonenzymic breakdown. It is suggested that the primary effect of this and the other compounds on porphyrin metabolism is a reduction in heme formation by a mechanism at present unclear.