Comprehensive Physiology 2013
DOI: 10.1002/cphy.c120006
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Porphyrin and Heme Metabolism and the Porphyrias

Abstract: Porphyrins and metalloporphyrins are the key pigments of life on earth as we know it, because they include chlorophyll (a magnesium-containing metalloporphyrin) and heme (iron protoporphyrin). In eukaryotes, porphyrins and heme are synthesized by a multistep pathway that involves eight enzymes. The first and rate-controlling step is the formation of delta-aminolevulinic acid (ALA) from glycine plus succinyl CoA, catalyzed by ALA synthase. Intermediate steps occur in the cytoplasm, with formation of the monopyr… Show more

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Cited by 161 publications
(177 citation statements)
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References 225 publications
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“…This established that the two enzymes required for uroporphyrinogen III production acted separately. As with the earlier enzymes in the pathway, much has been learned about HmbS and UroS from human genetic disorders that cause porphyria, in these cases acute intermittent porphyria and congenital erythropoietic porphyria, respectively (105).…”
Section: From Porphobilinogen To Tetrapyrrolementioning
confidence: 99%
“…This established that the two enzymes required for uroporphyrinogen III production acted separately. As with the earlier enzymes in the pathway, much has been learned about HmbS and UroS from human genetic disorders that cause porphyria, in these cases acute intermittent porphyria and congenital erythropoietic porphyria, respectively (105).…”
Section: From Porphobilinogen To Tetrapyrrolementioning
confidence: 99%
“…Mutations in each of the eight enzymes involved in the heme biosynthetic pathway are asso-ciated with inherited porphyrias (3)(4)(5). Among the porphyrias, erythropoietic protoporphyria (EPP) and X-linked-dominant protoporphyria (XLP) result in the accumulation of PP-IX (4).…”
Section: Protoporphyrin-ix (Pp-ix)mentioning
confidence: 99%
“…Our results suggest that direct porphyrin damage via induction of protein aggregation is likely to be fundamental to the pathogenesis of the disease and its symptom complex, especially in the cases of cutaneous porphyrias and its associated photosensitivity (4). Of note, symptoms of porphyria remit and relapse (3,5), so an attractive model is that symptom exacerbation is caused by an acute porphyrinogenic stress that results in protein aggregation and cell dysfunction. The exacerbation would then be cleared by refolding of the aggregates by induction of an unfolded protein response, normalization of the inhibition of the proteasome, or potential activation of autophagy to clear the aggregate.…”
Section: Protein Aggregation As a Mechanism Of Cell Injury Inmentioning
confidence: 99%
“…Drugs such as barbiturates, bernegride, chloramphenicol, chlordiazepoxide, chloroquine, chlorpropamide, danazol, diazepam, ergot preparations, estrogens, ethanol excess, griseofulvin, halothane, hydantoins, imipramine, ketamine, meprobamate, methyldopa, methyprylon, methsuximide, nikethamide, oral contraceptives, pentazocine, phensuximide, phenylbutazone, progestogens, pyrazinamide, pyrazolone derivatives, sulfonamides, theophylline derivatives, tolbutamide, troxidone and valproic acid (Bonkowsky et al, 1982) have been reported to exacerbate acute porphyrias. These drugs should thus be administered with caution in patients with an encephalopathy associated with porphyria.…”
Section: Drugmentioning
confidence: 99%