Effect of prolonged fasting on heme metabolism in the rat

It is known that fasting may provoke an acute attack in patients with latent hepatic porphyrias. We examined the influence of fasting on some aspects of heme synthesis in rats. Urinary excretion of both uroporphyrin and coproporphyrin, as well as fecal elimination of protoporphyrin and coproporphyrin, were increased on fasting. These biochemical aberrations resemble those found in subjects with latent porphyria variegata, suggesting that fasting rats may constitute an experimental model for latent variegate porphyria. The administration of phenobarbitone had a pronounced, synergistic effect on the urinary excretion of porphyrins. The activity of delta-aminolevulinic acid synthase (ALAS) and the concentration of cellular heme were determined in homogenates and subcellular fractions of the livers of fasting rats. A marked increase in the concentration of heme in the homogenate, the nuclei and the postmicrosomal supernatant fractions was observed. ALAS activity in the homogenate and the supernatant fraction increased while that in the mitochondria decreased. The possible relationship of these results to the human disease is discussed.