L-tryptophan: a common denominator of biochemical and neurological events of acute hepatic porphyria?

See allHide authors and affiliations

Science  02 Dec 1983:
Vol. 222, Issue 4627, pp. 1031-1033
DOI: 10.1126/science.6648517


Hepatic porphyrias are disorders of heme synthesis characterized by genetically determined lesions of one of the key enzymes of heme synthesis. In carriers of such lesions, several factors (drugs, environmental chemicals, or diet) precipitate acute and often fatal attacks of neurologic dysfunction, which are promptly relieved by intravenous infusion of heme. However, the mechanism of such heme-induced amelioration remains elusive. To probe this mechanism, the biochemical events triggered by acute hepatic heme deficiency were examined in an animal model of chemically induced porphyria. Acute hepatic heme depletion in porphyric rats was found to impair hepatic tryptophan pyrrolase activity which, in turn, elevated tryptophan and 5-hydroxytryptamine turnover in the brain. These alterations in porphyric rats were dramatically reversed by parenteral heme administration. These findings suggest that increased tryptophan and 5-hydroxytryptamine in the nervous system may be responsible for the neurologic dysfunctions observed in humans with acute attacks of hepatic porphyria.

Stay Connected to Science

Editor's Blog