Heme Biosynthesis in Intermittent Acute Porphyria: Decreased Hepatic Conversion of Porphobilinogen to Porphyrins and Increased Delta Aminolevulinic Acid Synthetase Activity
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TLDR
A micro-radio-chemical assay of delta-aminolevulinic acid synthetase, and some of its applications, are described, and this first and rate-controlling enzyme in the biosynthetic pathway is subject to negative feedback regulation by the end product, heme.Abstract:
Hepatic conversion of porphobilinogen to porphyrins was less than 50% of control levels in human subjects with the genetic disease, intermittent acute porphyria. This relative block in heme biosynthesis may be relevant to a concomitant 6- to 10-fold elevation in δ-aminolevulinic acid synthetase activity, since this first and rate-controlling enzyme in the biosynthetic pathway is subject to negative feedback regulation by the end product, heme. A micro-radio-chemical assay of δ-aminolevulinic acid synthetase, and some of its applications, are described.read more
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Journal ArticleDOI
The Role of Iron in the Pathogenesis of Porphyria Cutanea Tarda: AN IN VITRO MODEL
TL;DR: The effect of ferrous ion provides a possible biochemical explanation for the excess production and excretion of uroporphyrin I in patients with PCT and the reversal of this defect by phlebotomy.
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The primary enzyme defect in hereditary coproporphyria
George H. Elder,J.O Evans,Nicholas Stuart Tudor Thomas,R Cox,MartinJ. Brodie,M. R. Moore,Abraham Goldberg,D.C Nicholson +7 more
TL;DR: Consideration of the probable relative activities of the enzymes of haem biosynthesis in the liver in H.C.C suggests that the acute attacks of porphyria occur when the activity of uroporphyrinogen-I-synthase becomes rate-limiting for haem synthesis.
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Control of 5-aminolevulinate synthase in animals.
TL;DR: A major challenge which now exists is to understand at the molecular level how the genes for ALV-synthase and cytochrome P-450 are regulated in the liver and other tissues.
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Decreased Hepatic Uroporphyrinogen Decarboxylase Activity in Porphyria Cutanea Tarda
TL;DR: It is concluded that reduced hepatic uroporphyrinogen decarboxylase activity is a specific and intrinsic hepatic defect in porphyria cutanea tarda, but modulation of uroporalinogen synthesis by extrinsic factors is required for the full biochemical expression of the disease.
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The Induction of δ-Aminolevulinic Acid Synthetase in Cultured Liver Cells THE EFFECTS OF END PRODUCT AND INHIBITORS OF HEME SYNTHESIS
TL;DR: Experiments with inhibitors of protein synthesis are consistent with a translational site for heme repression, and a mechanism whereby drugs may induce δ-aminolevulinic acid synthetase by interfering with heme synthesis is demonstrated.