Haem arginate improves hepatic oxidative metabolism in variegate porphyria.

Tokola, Olavi; Mustajoki, Pertti; Himberg, Jaakko‐Juhani

doi:10.1111/j.1365-2125.1988.tb05315.x

Cited by 11 publications

(5 citation statements)

References 22 publications

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“…Tin protoporphyrin, other metalloporphyrins and heme reduce ALA synthase activity (6, 20, 22, 23, 36, 371, and these compounds have been used to reduce overproduction of heme precursors in patients with acute porphyria (12)(13)(14)(15)36,38). Tin-chelated porphyrins can cause cutaneous photosensitivity (36, 40-42,44,45) and are not readily catabolized in viva (36, 46, 651, raising concerns about possible long-term adverse effects of these compounds (41-45).…”

Section: Discussionmentioning

confidence: 99%

“…Activity of this enzyme is elevated in human subjects with acute porphyria , in whom occurrence of clinical illness is associated with increased excretion of porphyrins and porphyrin precursors, the biochemical hallmarks of the acute porphyrias. The treatment of choice for all but the mildest attacks of acute porphyria is intravenous heme (11)(12)(13)(14)(15), first described 22 yr ago (15). Heme reduces hepatic ALA synthase levels in various experimental models of acute porphyria (16)(17)(18)(19) and undoubtedly has the same effect in patients with acute porphyria (11)(12)(13)(14)(15).…”

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confidence: 99%

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Repression of hepatic δ-aminolevulinate synthase by heme and metalloporphyrins: Relationship to inhibition of heme oxygenase

Cable

Bonkovsky

1993

Hepatology

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Heme- and tin-chelated metalloporphyrins are known to decrease the activity of hepatic delta-amino-levulinate synthase, the rate-controlling enzyme of heme synthesis. We performed experiments in primary chick embryo liver cells with tin-, zinc- and copper-chelated porphyrins to assess their effects on activities of delta-aminolevulinate synthase induced by prior treatment of cells with glutethimide and ferric nitrilotriacetate. These different metalloporphyrins were tested to form the experimental foundation for eventual studies in patients with acute porphyrias, in which uncontrolled induction of hepatic delta-amino-levulinate synthase, which plays a key role in pathogenesis of disease. Zinc and tin porphyrins reduced delta-aminolevulinate synthase activities, whereas copper-chelated porphyrins did not. When heme (iron protoporphyrin) was added with zinc or tin porphyrins, delta-aminolevulinate synthase activity was further reduced. Effects of the nonheme metalloporphyrins on delta-aminolevulinate synthase were closely correlated with their abilities to inhibit heme oxygenase (r = 0.78). The largest decrease of delta-aminolevulinate synthase (67%) was obtained with zinc mesoporphyrin and heme. Dose-response data indicated that only nanomolar concentrations of zinc mesoporphyrin and heme are required to obtain this effect. We found no effect of exposure to heme (10 mumol/L) or heme (200 nmol/L) plus zinc mesoporphyrin (50 nmol/L) on the half-life of activity of delta-aminolevulinate synthase (1.9 to 2.1 hr, regardless of treatment). This result suggests that the repressive effect of heme is directed toward decreasing synthesis, increasing breakdown or decreasing the translation of the messenger RNA of delta-aminolevulinate synthase.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Repression of hepatic δ-aminolevulinate synthase by heme and metalloporphyrins: Relationship to inhibition of heme oxygenase

Cable

Bonkovsky

1993

Hepatology

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“…In human studies on acute porphyrias, exogenous heme corrects impairments in hepatic oxidative drug metabolism and normalizes porphyrin overproduction in variegate porphyria. 126 It is effective in repleting deficient heme pools and heme proteins, 118 in increasing Cyp450 activity in AIP 127 and has an isoenzyme-specific influence on Cyp450 drug metabolism. 128 Heme is the prosthetic group in many important liver enzymes and is involved in regulating the amount and activity of cytochrome P450.…”

Section: Prelude To Liver Transplantationmentioning

confidence: 99%

Liver Transplantation in Acute Hepatic Porphyria and Erythropoietic Protoporphyria

Wåhlin¹,

Harper²

2013

Handbook of Porphyrin Science (Volume 29)

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“…In 1987 Herrick et al in Scotland [ 79 ] treated seven attacks in five patients: decrease of 5-ALA and PBG and improvement of clearance of antipyrin (which is degraded in the liver by CYP enzymes) were observed. In 1988 Tokola et al, (Finland) reported on six patients with VP with respect to antipyrin clearance [ 80 ]. In 1988 Volin et al [ 81 ] did not find adverse effects on hemostasis in healthy volunteers treated with heme arginate.…”

Section: Therapymentioning

confidence: 99%

Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know

Petrides

2022

Diagnostics

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Heme, iron protoporphyrin IX, is one of life’s most central molecules. Hence, availability of the enzymatic machinery necessary for its synthesis is crucial for every cell. Consequently, inborn errors of porphyrin metabolism that compromise normal synthesis, namely the family of porphyrias, undermine normal cellular metabolism given that heme has functions in catalytic centers, signal transduction and functional regulation and its synthesis is fully integrated into the center of intermediary metabolism. Very often, diagnosis of porphyrias is difficult and therefore delayed. Therapy can be as complicated. Over the last 50 years, several strategies have been developed: because of its integration with other parts of intermediary metabolism, the infusion of glucose (glucose effect) was one of the first attempts to counterbalance the dysregulation of porphyrin synthesis in porphyrias. Since heme synthesis is impaired, infusional replacement of heme was the next important therapeutic step. Recently, siRNA technology has been introduced in order to downregulate 5-ALA-synthase 1, which contributes to the patho-physiology of these diseases. Moreover, other novel therapies using enzyme protein replacement, mRNA techniques or proteostasis regulators are being developed.

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Haem arginate improves hepatic oxidative metabolism in variegate porphyria.

Cited by 11 publications

References 22 publications

Repression of hepatic δ-aminolevulinate synthase by heme and metalloporphyrins: Relationship to inhibition of heme oxygenase

Repression of hepatic δ-aminolevulinate synthase by heme and metalloporphyrins: Relationship to inhibition of heme oxygenase

Liver Transplantation in Acute Hepatic Porphyria and Erythropoietic Protoporphyria

Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know

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