Measurement of δ-Aminolevulinic Acid Synthetase Activity in Human Erythroblasts

Aoki, Yosuke; Urata, Gumpei; Wada, Osamu; Takaku, Fumimaro

doi:10.1172/jci107680

Cited by 63 publications

(31 citation statements)

References 20 publications

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“…Among primary sideroblastic of NADH anemias the most frequent type is the primary acquired absorbance type. Almost all the symptoms of this disorder can be ase activity ascribed to the impaired heme synthesis resulting from bytes of the the decreased ALA synthetase activity in erythroblasts observed, (1,2). In fact, every patient with primary sideroblastic re granulo-anemia, including that with primary acquired type, tients with had decreased ALA synthetase activity in erythroblasts hin normal as shown in Fig.…”

Section: Methodsmentioning

confidence: 97%

“…Cellular components of bone marrow aspirate that were suspended in 20 ml of saline were filtered through four layers of gauze, and the filtrate was layered on a separating medium consisting of two parts (10 ml Midland, Mich.) 50 x 8 W column chromatography to be counted by a liquid scintillation counter as described (2). 1 U was defined as the enzyme activity producing 1 nmol of ALA in 30 min under the conditions described (2).…”

Section: Methodsmentioning

confidence: 99%

“…1. The decrease of this enzyme ranulocytes activity in erythroblasts of the patients is considered tients with not to be secondary to iron deposition in mitochondria the normal but to be the primary defect in erythroblasts (1,2).…”

Section: Methodsmentioning

confidence: 99%

“…Ferrokinetic studies usually show accelerated plasma iron disappearance with impaired iron incorporation into erythrocytes. Almost all features characteristic ofthis disease can be ascribed to a disturbance of heme synthesis in erythroblasts (1,2). In fact, the activity of 8-aminolevulinic acid (ALA)' synthetase, the rate-limiting enzyme in heme synthesis is inevitably decreased in erythroblasts of patients with primary sideroblastic anemia (2).…”

Section: Introductionmentioning

confidence: 99%

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Multiple Enzymatic Defects in Mitochondria in Hematological Cells of Patients with Primary Sideroblastic Anemia

Aoki¹

1980

J. Clin. Invest.

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A B S T R A C T Activities of mitochondrial enzymes in blood cells from 69 patients with primary sideroblastic anemia were determined to elucidate the pathogenesis ofthe disease. In erythroblasts of patients with primary acquired type the activities of both 8-aminolevulinic acid synthetase and mitochondrial serine protease were inevitably decreased. The susceptibility to the protease of apo-8-aminolevulinic acid synthetase prepared from erythroblasts of patients with this type was within the normal range, in contrast to that of pyridoxineresponsive anemia. The activities of mitochondrial enzymes such as cytochrome oxidase, serine protease, and oligomycin-sensitive ATPase, except citrate synthetase, were usually decreased in mature granulocytes of the patients. Patients with hereditary sideroblastic anemia also had decreased 8-aminolevulinic acid synthetase activity in erythroblasts, and decreased serine protease activity in both erythroblasts and mature granulocytes. Mature granulocytes obtained from patients with pyridoxine-responsive anemia before therapy had decreased cytochrome oxidase activity, however, the activity increased to a normal level when the patients were in remission. The activities of other mitochondrial enzymes in mature granulocytes were within normal range in these patients before pyridoxine therapy. The activities of these mitochondrial enzymes in lymphocytes were within normal range in all groups of patients with primary sideroblastic anemia.We suggest that patients with primary acquired, and possibly also those with hereditary sideroblastic anemia have impaired mitochondrial function in both erythroblasts and granulocytes. That only anemia is observed in these patients is because a functional abnomiality of mitochondria in erythroblasts is most important because of the role of mitochondria in the fomiation of heme in erythrocyte development. In con-

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Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multiple Enzymatic Defects in Mitochondria in Hematological Cells of Patients with Primary Sideroblastic Anemia

Aoki¹

1980

J. Clin. Invest.

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“…ALA synthetase is known as the rate-limiting enzyme in heme synthetic pathway (8). Almost all heinatological features characteristic to pyridoxine-responsive anemia could be ascribed to tlhe disturbance of hemne synthesis in erythroblasts (9). ALA synthetase activity in erythroblasts of patients with primary sideroblastic anemia including those with pyridoxine-responsive anemia was already shown to be inevitably decreased (9).…”

Section: Introductionmentioning

confidence: 99%