Altered 5-aminolevulinic acid metabolimn leading to pseudoporphyria in hemodialysed patients

Guolo, M.; Stella, Ana María; Melito, Viviana Alicia; Parera, Victoria Estela; Batlle, Alcira

doi:10.1016/1357-2725(95)00133-6

Cited by 14 publications

(20 citation statements)

References 27 publications

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“…With reference to the ALA-D activity increase when increasing volumes of normal plasma were added to the incubation mixture, since zinc ions are involved in the enzyme functional dimer, it is possible that different zinc levels (from different volumes of normal plasma added) could affect ALA-D activity. On the other hand, this effect is less important when ALA-D activity of HD plasma is analyzed because – as it was already reported by Guolo et al [2]– HD plasma has a lower zinc concentration.…”

Section: Discussionmentioning

confidence: 69%

“…The activity of aminolevulinate dehydratase (ALA-D) has been shown to be diminished in red blood cells (RBC) from hemodialyzed (HD) patients [1, 2]as well as in experimental CRF [3, 4, 5]. This decreased activity can be attributed to either reduced enzyme synthesis or inhibition.…”

Section: Introductionmentioning

confidence: 99%

“…This decreased activity can be attributed to either reduced enzyme synthesis or inhibition. It has been suggested that these alterations could be due to lower plasma zinc concentrations [2]or to the presence of toxic metals such as lead [6]or aluminium [7]. Addition of zinc slightly increased RBC ALA-D activity from HD patients; however, values obtained were always significantly lower than those reached by adding zinc to normal RBC [2].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Erythrocyte Aminolevulinate Dehydratase by a 56.2-kD Peptide from Uremic Plasma

Guolo

Machalinski

Biscoglio

et al. 1999

Nephron Exp Nephrol

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Among the abnormalities in erythrocyte porphyrin metabolism already described in patients with chronic renal failure on hemodialysis, a decrease in blood aminolevulinate dehydratase activity has been reported, suggesting the presence in uremic plasma of an inhibitor of the enzyme. The aim of this work has been to isolate and characterize such an inhibitor. Blood samples from 105 patients with chronic uremia were collected; plasma was applied to Sephadex G-100 columns and the fraction with the highest inhibiting capacity was identified and purified by subsequent SDS-polyacrylamide gel electrophoresis, followed by electroelution and electroblotting. It was demonstrated that the factor present in plasma of uremic patients inhibited blood aminolevulinate dehydratase in a concentration-dependent manner; its inhibitory properties were abolished after heat, trypsin and TCA treatment indicating its peptidic nature. The purified inhibitor has an apparent molecular mass of 56.2 kD, it inhibits blood aminolevulinate dehydratase in a competitive way and the K_i value is 12×10^–6 M. The amino acid composition of the inhibitor has been determined and it has been found that its N-terminal amino acid is blocked. The isolated peptide may play a role in heme biosynthesis disturbances and in the pathogenesis of uremic anemia.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Erythrocyte Aminolevulinate Dehydratase by a 56.2-kD Peptide from Uremic Plasma

Guolo

Machalinski

Biscoglio

et al. 1999

Nephron Exp Nephrol

View full text Add to dashboard Cite

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“…Common features in patients with chronic renal failure (CRF) under hemodialysis treatment (HD) are erythrocyte aminolevulinate dehydratase (ALAD) (EC 4.2.1.24) hypoactivity and enhanced blood porphyrin levels, mainly protoporphyrin IX (PPIX) [1, 2, 3, 4]. Similar abnormalities in the heme pathway have also been observed in two experimental models where renal failure has been induced by nephrectomy or cyclosporin administration and in experimental acute renal failure.…”

Section: Introductionmentioning

confidence: 65%

“…Plasma from these HD patients showed the ability to inhibit erythrocyte ALAD activity from healthy subjects [1, 3, 4, 5, 6, 7]and because the same inhibitory ability has been detected before and after dialysis, it was hypothesized [1, 5]that the inhibitor factor was not dialyzable.…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin Content Is Increased in the Human Erythroleukemia K562 Cell Line by a 56.2-kD Peptide from Uremic Plasma

et al. 2004

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Background: Some abnormalities in porphyrin metabolism have been described in erythrocytes from patients with end-stage renal failure. A peptidic fraction of 56.2 kD isolated from plasma of these patients was previously identified as an aminolevulinate dehydratase inhibitor. The aim of this study was to examine the in vitro effect of this peptide on heme synthesis in the erythroleukemia K562 cells. Methods: The 56.2-kD fraction was purified from uremic plasma by protein electroelution and, its action on the mitochondrial rate-limiting steps of heme synthesis, as well as the hemoglobin content during erythroid differentiation induced by sodium butyrate, was investigated in K562 cells. Results: Two hours after addition of the 56.2-kD peptide, the activities of aminolevulinate acid synthase and aminolevulinate dehydratase were reduced while the activity of the ferrochelatase was enhanced, indicating that this peptide easily across the membranes. A 3-day incubation with this peptide enhanced approximately twofold the hemoglobin and porphyrin levels during erythroid differentiation of K562 cells without variation of cell growth. Conclusion: This study shows that the addition of the 56.2-kD uremic factor to K562 cells was clearly implicated in heme disturbances existing in chronic renal failure but it did not play a negative role in the pathogenesis of the uremic anemia.

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Porphyria Diagnostics—Part 1: A Brief Overview of the Porphyrias

2015

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The porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by the excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), delta-aminolevelunic acid dehyratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoetic porphyria (HEP), congenital erythropoetic porphyria (CEP), erythropoetic protoporphyria (EPP), and X-linked protoporphyria (XLP). Each porphyria results from overproduction of heme precursors secondary to partial deficiency or, in XLP, increased activity of one of the enzymes of heme biosynthesis. Taken together, all forms of porphyria afflict fewer than 200,000 people in the United States. Based on European studies, the prevalence of the most common porphyria, PCT, is 1 in 10,000, the most common acute porphyria, AlP, is about 1 in 20,000, and the most common erythropoietic porphyria, EPP, is estimated at 1 in 50,000 to 75,000. CEP is extremely rare with prevalence estimates of 1 in 1,000,000 or less. Only 6 cases of ADP are documented. The current porphyria literature is very exhaustive and a brief overview of porphyria diseases is essential in order for the reader to better appreciate the relevance of this area of research prior to undertaking biochemical diagnostics procedures. This unit summarizes the current knowledge on the classification, clinical features, etiology, pathogenesis, and genetics of these porphyria diseases.

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Altered 5-aminolevulinic acid metabolimn leading to pseudoporphyria in hemodialysed patients

Cited by 14 publications

References 27 publications

Inhibition of Erythrocyte Aminolevulinate Dehydratase by a 56.2-kD Peptide from Uremic Plasma

Inhibition of Erythrocyte Aminolevulinate Dehydratase by a 56.2-kD Peptide from Uremic Plasma

Hemoglobin Content Is Increased in the Human Erythroleukemia K562 Cell Line by a 56.2-kD Peptide from Uremic Plasma

Porphyria Diagnostics—Part 1: A Brief Overview of the Porphyrias

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