Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis

Martini, Claudia; Romero, Damián G.; Yanes, Licy L.; Vila, María del Carmen

doi:10.1016/j.lfs.2007.04.020

Cited by 6 publications

(2 citation statements)

References 39 publications

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“…Low salt diet and adrenocorticotropic hormone or endothelin-1 infusion in rats increased ALAS1 expression in the adrenal gland which suggests that the production of active cytochromes involved in adrenal steroid synthesis may also induce the haem synthesis pathway. 130 This is also supported by the fact that ALAS1 expression is higher in tissues producing steroid hormones such as testis and adrenal gland. 28 …”

Section: E Hormonal Regulationmentioning

confidence: 88%

Complicity of haem in some adverse drug-reactions

Vágány

Smith

2015

Toxicol. Res.

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Adverse drug reactions are often idiosyncratic responses to administered medicines or herbal remedies that may be the consequence of multiple interactions between physiological and genetic factors with drug target and off-target effects. Identification and resolution of the mechanisms of these factors for individuals can prove problematic. Genetic variants or acquired fluctuations in the activity of the haem metabolism enzymes are well established predisposition factors in some known clinical hepatic disorders.Some of these disorders of nonerythroid haem supply can be triggered by drugs, hormones and other agents that normally have no untoward effects. Thus these mutations affecting the activity of the enzymes in the haem pathway can be regarded as predisposing genetic factors causing adverse reactions of some drugs in susceptible individuals. Carriers may be non-symptomatic for a prolonged period until the combination of factors such as consumption of medicinal products, alcohol, stress, hormone fluctuations and change in dietary habits trigger clinical symptoms. Despite these inherited or acquired changes of the haem metabolic pathway, many carriers do not develop symptoms illustrating the involvement of other unknown genetic components. In addition, haem is of fundamental cellular importance not only for respiratory cytochromes and oxygen transport but for many other roles such as for cytochrome P450, NO signalling, and microRNA formation. For these reasons, nonerythroid haem synthesis is under complex transcriptional and translational regulation linked to age, nutrition and circadian rhythm and to hormonal, drug and stress responses. Besides those already known, interference and genetic differences in the flux of supply, recruitment and use of haem for such fundamental processes may contribute to adverse drug reactions in metabolic arenas that are not yet recognised.

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Section: E Hormonal Regulationmentioning

confidence: 88%

Complicity of haem in some adverse drug-reactions

Vágány

Smith

2015

Toxicol. Res.

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“…49 Induction of ALA-S1 Via Metabolic Signaling Some nuclear signaling, such as peroxisome proliferatoractivated receptor-gamma coactivator 1α (PGC-1α), which is involved in a different manner in the endogenous regulation of many metabolic pathways, can take part in the global inductive process of the ALA-S1 activation, which explains why the ALA-S1 transcription is also controlled by some endocrine-metabolic circuits (starvation, gonadal activity, activity of the hypothalamic-hypophysis-adrenal axis, hormone signaling, etc), whose interference may have porphyrogenic effects. 34,40,[50][51][52][53][54] Induction of ALA-S1 Via the Induction of Heme-Oxygenase Expression Agents or conditions that upregulate heme oxygenase, the main enzyme of heme catabolism, may be considered as porphyrogenic; they cause an increase in heme catabolism, thus reducing free heme pool concentrations and activating ALA-S1 transcription. Well-known inducers of HO-1 are stress, fasting, endotoxins, heavy metals, and organic solvents.…”

Section: Mechanisms Of Drug Porphyrogenicitymentioning

confidence: 99%

Drugs and Acute Porphyrias: Reasons for a Hazardous Relationship

Roveri

Nascimbeni

Rocchi

et al. 2014

Postgraduate Medicine

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The porphyrias are a group of metabolic diseases caused by inherited or acquired enzymatic deficiency in the metabolic pathway of heme biosynthesis. Simplistically, they can be considered as storage diseases, because the partial enzymatic defect gives rise to a metabolic "bottleneck" in the biosynthetic pathway and hence to an accumulation of different metabolic intermediates, potentially toxic and responsible for the various (cutaneous or neurovisceral) clinical manifestations observed in these diseases. In the acute porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and the very rare delta-aminolevulinic acid dehydratase ALAD-d porphyria), the characteristic severe neurovisceral involvement is mainly ascribed to a tissue accumulation of delta-aminolevulinic acid, a neurotoxic nonporphyrin precursor. Many different factors, both endogenous and exogenous, may favor the accumulation of this precursor in patients who are carriers of an enzymatic defect consistent with an acute porphyria, thus contributing to trigger the serious (and potentially fatal) clinical manifestations of the disease (acute porphyric attacks). To date, many different drugs are known to be able to precipitate an acute porphyric attack, so that the acute porphyrias are also considered as pharmacogenetic or toxygenetic diseases. This article reviews the different biochemical mechanisms underlying the capacity of many drugs to precipitate a porphyric acute attack (drug porphyrogenicity) in carriers of genetic mutations responsible for acute porphyrias, and addresses the issue of prescribing drugs for patients affected by these rare, but extremely complex, diseases.

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