Regulation of σ-Aminolevulinic Acid Synthetase by Drugs and
Steroids in Isolated Perfused Rat Liver

Kw, Bock; Weiner, Rachel; Fröhling, W

doi:10.1159/000459393

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…Therefore the non-porphyrogenic analogues of 3,5-diethoxycarbonyl-1,4-dihydrocollidine and griseofulvin are capable ofstimulating the production ofintermediates of the pathway in the liver, but can only do this when the rat has been 'primed' with 3,5-diethoxycarbonyl-1,4-dihydrocollidine. This is similar to previous findings obtained with several lipid-soluble drugs, including phenobarbitone, which are not porphyrogenic on their own, but can all potentiate the stimulation of 5-aminolaevulinate synthetase and the porphyria caused by porphyrogenic drugs (De Matteis & Gibbs, 1972;De Matteis, 1973;Bock et al, 1973;Padmanaban et al, 1973).…”

Section: Resultssupporting

confidence: 91%

Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms

Matteis

Gibbs

1975

Biochemical Journal

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Griseofulvin and isogriseofulvin cause, like 3,5-diethoxycarbonyl-1,4-dihydrocollidine, a fall in the activity of the hepatic enzyme porphyrin-metal chelatase and accumulation of protoporphyrin in the liver. Analogues of either griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine which do not decrease the chelatase activity are not porphyrogenic on their own, but can potentiate the porphyria caused by 3,5-diethoxycarbonyl-1,4-dihydrocollidine. This suggests the existence of two basically different mechanisms by which drugs stimulate the pathway of porphyrin synthesis in the liver.

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Section: Resultssupporting

confidence: 91%

Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms

Matteis

Gibbs

1975

Biochemical Journal

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“…The two mechanisms discussed above for the stimulation of the liver enzyme, the one dependent on haem depletion and that related to lipid-soluble drugs, can potentiate each other, as shown by the much greater stimulation of enzyme activity caused by phenobarbitone in the liver when haem biosynthesis is inhibited by either 3 J-diet hox ycarbon yl-1,4-dihydrocollidine or by lead (De Matteis, 1973;Bock et al, 1973;Maxwell and Meyer, 1976). In addition, the liver 5-aminolaevulinate synthase can be stimulated by the administration of several chemically unrelated drugs (including phenobarbitone) that have in common the property of lipidsolubility.…”

Section: Inhibition Of Cerebellar Haem Biosynthesis Caused By Succinymentioning

confidence: 99%

“…The mechanism of this second, drugmediated effect on the enzyme is still unclear, but may be related to the property that many drugs possess of enlarging the liver and of inducing its drugmetabolizing system. The two mechanisms discussed above for the stimulation of the liver enzyme, the one dependent on haem depletion and that related to lipid-soluble drugs, can potentiate each other, as shown by the much greater stimulation of enzyme activity caused by phenobarbitone in the liver when haem biosynthesis is inhibited by either 3 J-diet hox ycarbon yl-1,4-dihydrocollidine or by lead (De Matteis, 1973;Bock et al, 1973;Maxwell and Meyer, 1976).…”

Section: Inhibition Of Cerebellar Haem Biosynthesis Caused By Succinymentioning

confidence: 99%

Studies on Cerebellar Haem Metabolism in the Rat In Vivo

Matters

Ray

1982

Journal of Neurochemistry

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Rats were injected intraventricularly with 5-amino[4-14C]laevulinate and the radioactivity recovered in the total cerebellum homogenate and in its haem and porphyrin fractions was determined in time. Two phases could be distinguished in the decline of haem radioactivity, suggesting labelling of at least two pools of widely different turnover rates. Succinyl acetone, when injected intraventricularly, caused a marked and long-lasting inhibition of cerebellar 5-aminolaevulinate dehydratase activity and a corresponding inhibition of the incorporation of [14C]5-aminolaevulinate into cerebellar haem in vivo. Inhibition of cerebellar haem biosynthesis by succinylacetone was followed by stimulation of the first enzyme of the pathway, 5-aminolaevulinate synthase, whereas intraventricular injection of haematin led to a significant depression of the activity of the enzyme. This suggested that the cerebellar 5-aminolaevulinate synthetase is regulated by haem through a negative feedback mechanism. Rats given repeated doses of succinylacetone, so as to maintain 80% inhibition of their cerebellar 5-aminolaevulinate dehydratase activity for 5 days, failed to exhibit any obvious symptoms of toxicity but became more sensitive to the neurotoxic effects of large intraventricular doses of 5-aminolaevulinate.

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“…The lack of a glucose effect in perfused liver is in contrast to a previous preliminary report [2] in which ALA synthetase was determined by a radio active method using the precursor 14C-succinate [5]. However, using this method changes in the endogenous succinate pool and its turnover can affect the enzyme determination.…”

Section: Discussionmentioning

confidence: 64%

Lack of Glucose Effect on the Induction of 5-Aminolevulinate Synthetase and Tyrosine Aminotransferase in the Isolated Perfused Rat Liver

Kw¹,

Weiner²,

Schultz³

1976

Enzyme

Self Cite

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In the isolated perfused rat liver, both 5-aminolevulinate synthetase and tyrosine aminotransferase were induced by the addition of 3.5 mmol/l allylisopropylacetamide and 58 μmol/l dexamethasone to the perfusion medium. Glucose (40 mmol/l) did not affect either the induction of these enzymes or the intrahepatic level of cyclic AMP. The results suggest that the glucose effect on the induction of 5-aminolevulinate synthetase and tyrosine aminotransferase in vivo is mediated by extrahepatic factors.

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Regulation of σ-Aminolevulinic Acid Synthetase by Drugs and Steroids in Isolated Perfused Rat Liver

Cited by 10 publications

References 12 publications

Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms

Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms

Studies on Cerebellar Haem Metabolism in the Rat In Vivo

Lack of Glucose Effect on the Induction of 5-Aminolevulinate Synthetase and Tyrosine Aminotransferase in the Isolated Perfused Rat Liver

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