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Conversion of liver haem into N‐substituted porphyrins or green pigments
Author(s) -
De Matteis F.,
Gibbs A.H.,
Jackson A.H.,
Weerasinghe Sunethra
Publication year - 1980
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(80)81009-x
Subject(s) - section (typography) , chemistry , library science , computer science , operating system
Drugs can promote the conversion of liver haem into modeled porphyrins (or green pigments) of two distinct classes. Pigments of the first class are obtained by treatment with unsaturated drugs containing at least one allyl, vinyl or ethynyl side chain. These drugs are metabolized by cytochrome P450 into reactive derivatives, which then become bound onto the porphyrin nucleus of the haem moiety of the cytochrome, converting it into modified porphyrins (reviewed in [I ,2]). The nature of the drug metabolite responsible is still controversial: epoxides have been suggested ([2] and references therein), but there is also a proposal [33 specifically excluding epoxides and emphasizing other structural features of the metabolite, such as the presence of an ‘activated’ carbony1 grouping. Green pigments of this class do not inhibit liver protohaem ferro-lyase [4] (the enzyme which converts protoporphyrin to haem) and for this reason none of the unsaturated drugs responsible will cause a very marked increase in liver protoporphyrin in v&o. In contrast 3,5-diethoxycarbonyl-1,4-d~ydrocollidine, griseofulvin and isogriseofulvin produce liver accumulation of a second type of green pigment with strong inhibitory properties towards protohaem ferrolyase in vitro [4-61. Marked inhibition of the liver enzyme is also observed in vivo after treatment with this second group of drugs [7,8] and as a consequence, the liver concentration of protoporphyrin increases markedly giving rise to the biochemical picture of hepatic protoporphyria. The ‘inhibitory’ pigment also appears to originate from turnover of liver haem [4],