Increased erythrocyte uroporphyrinogen-I-synthetase, δ-aminolevulinic acid dehydratase and protoporphyrin in hemolytic anemias

Anderson, Karl E.; Sassa, Shigeru; Peterson, Charles M.; Kappas, Attallah

doi:10.1016/0002-9343(77)90273-x

Cited by 58 publications

(18 citation statements)

References 14 publications

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“…The specific PBG-S activities are higher in bone marrow cells than in peripheral erythrocytes ( Table 2). Age-dependent factors influence the activity of PBG-S. Activity of the heme-synthesis enzymes ALA synthase, uroporphyrinogen synthase, and ferrochetatase decreases throughout normoblast maturing and hemoglobin formation [1,20]; activity of the mitochondrial enzymes ALA synthase and ferrochelatase fade completely on the reticulocyte level, whereas the activity of uroporphyrinogen synthase can still be demonstrated in peripheral erythrocytes [8]. Our findings show a similar development of PBG-S activity during the course of erythrocytopoiesis (Table 2).…”

Section: Resultssupporting

confidence: 73%

“…In analogy to the above-mentioned enzymes of porphyrinogen and heine biosynthesis, the specific activity of PBG-S decreases throughout cell maturation. Protoporphyrin belongs to the proximal heine-synthesis components which decrease in concentration during the course of erythrocytopoiesis [1]. Concentration decreases not only in healthy individuals, it also decreased in the two porphyria patients without returning to normal ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

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Porphobilinogen-synthase (?-aminolevulinic acid dehydratase) deficiency in bone marrow cells of two patients with porphobilinogen-synthase defect acute porphyria

1983

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Two male patients aged 23 and 25 years with intermittent acute, frequently repeated porphyria syndromes presented an almost total deficiency of porphobilinogen-synthase [(PBG-S); synonym: delta-aminolevulinic acid dehydratase] in peripheral erythrocytes. PBG-S was investigated in bone marrow cells obtained by sternal puncture. A minimal enzyme activity of less than 3% of controls was established. Specific activity and protoporphyrin concentration decreased considerably during the course of erythropoiesis. Both patients are homozygous gene carriers; their parents (father and mother) as well as most of their brothers and sisters are heterozygotes with a PBG-S deficiency of approximately 50% of controls. All people with PBG-S deficiency are especially endangered by alcohol intake and lead exposure, because alcohol and lead toxically inhibit PBG-S.

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Section: Resultssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Porphobilinogen-synthase (?-aminolevulinic acid dehydratase) deficiency in bone marrow cells of two patients with porphobilinogen-synthase defect acute porphyria

1983

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“…3). However, in contrast to previ ous observations, this finding could not be related to either iron deficiency [49] or young RBC age [50], Thus, it is likely that other factors modify heme syn thesis in CHD subjects. Indeed, we recently noted that RBC protoporphyrin was increased in 8 of 26 CHD patients with aluminium overload and values returned to normal in 4 of the 5 patients treated with deferoxamine [51].…”

Section: Discussioncontrasting

confidence: 99%

Prospective Controlled Study of Androgen Effects on Red Cell Oxygen Transport and Work Capacity in Chronic Hemodialysis Patients

Hendler¹,

Solomon²

1990

Acta Haematol

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Effects of androgens on red blood cell (RBC) oxygen transport, RBC metabolism and work capacity in chronic hemodialysis patients were evaluated in a prospective controlled study. Compared to control subjects, patients given nandrolone decanoate had a sustained fall in RBC ATP and a transient rise in RBC DPG but P50 values were unchanged. Despite increases in RBC mass of 16–44% on androgen therapy, excercise on the treadmill improved in only 1 patient and actually declined in 3 others. Thus, these preliminary observations suggest that androgens may not improve hemoglobin-oxygen transport and that androgen-induced increases in red cell mass may only balance increased tissue oxygen requirements produced by these anabolic hormones.

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“…There are, however, limitations to this approach as a screening method. Erythrocyte PBGD levels are affected by erythrocyte age and the presence of other diseases (2), and there is some overlap between values for normal individuals and AIP patients (1). In addition, some families have been described with clinical and biochemical criteria indicating AIP, but without the PBGD deficiency in the erythrocytes of the patients (3)(4)(5); in fact the distribution of PBGD activity in these AIP patients and their relatives is identical to that in healthy controls (3,5), in contrast to most AIP families in which erythrocyte PBGD levels show a biphasic distribution.…”

mentioning

confidence: 99%

Tissue-specific splicing mutation in acute intermittent porphyria.

Grandchamp

Picat

Mignotte

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

102

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An inherited deficiency of porphobilinogen deaminase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G --A) in the canonical 5' splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using oligonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families.Acute intermittent porphyria (AIP) is a metabolic disorder characterized by attacks of neurological dysfunction with abdominal pain, hypertension, tachycardia, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors (1). AIP results from a partial deficiency of the third enzyme of heme biosynthesis, porphobilinogen deaminase [PBGD; porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] that is inherited as an autosomal dominant trait (1). Early detection of gene carriers is important in the prevention of attacks, as they can be advised to avoid precipitating factors. Since asymptomatic carriers do not consistently excrete abnormal amounts of porphyrins and the porphyrin precursors, 5-aminolevulinic acid and porphobilinogen, the best method for detecting carriers in most AIP families is the determination of erythrocyte PBGD activity (1). There are, however, limitations to this approach as a screening method. Erythrocyte PBGD levels are affected by erythrocyte age and the presence of other diseases (2), and there is some overlap between values for normal individuals and AIP patients (1). In addition, some families have been described with clinical and biochemical criteria indicating AIP, but without the PBGD deficiency in the erythrocytes of the patients (3-5); in fact the distribution of PBGD activity in these AIP patients and their relatives is identical to that in healthy controls (3, 5), in contrast to most AIP families in which erythrocyte PBGD levels show a biphasic distribution. These features point to the existence of a subset of AIP families in whom the mutation is not expressed in erythrocytes.We demonstrated (6) that two isoforms of PBGD, one found in nonerythroid cells and the other found only in erythroid cells, are translated from two mRNAs that differ solely in their 5' termini. These mRNAs are produced through alte...

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Increased erythrocyte uroporphyrinogen-I-synthetase, δ-aminolevulinic acid dehydratase and protoporphyrin in hemolytic anemias

Cited by 58 publications

References 14 publications

Porphobilinogen-synthase (?-aminolevulinic acid dehydratase) deficiency in bone marrow cells of two patients with porphobilinogen-synthase defect acute porphyria

Porphobilinogen-synthase (?-aminolevulinic acid dehydratase) deficiency in bone marrow cells of two patients with porphobilinogen-synthase defect acute porphyria

Prospective Controlled Study of Androgen Effects on Red Cell Oxygen Transport and Work Capacity in Chronic Hemodialysis Patients

Tissue-specific splicing mutation in acute intermittent porphyria.

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