Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum aldolase A (ALD-A) levels were determined in patients with leukemia using a radioimmunoassay method. The method is a double antibody radioimmunoassay consisting of purified ALD-A as ligand, chicken antisera to ALD-A and rabbit antibodies to chicken IgG. Serum ALD-A levels of 41 normal healthy subjects ranged from 130 to 210 ng/ml (mean +/- 2 SD; 171 +/- 39 ng/ml). Serum ALD-A levels ranged from 90 to 200 ng/ml in patients with 42 non-neoplastic hematological diseases with the exception of hemolytic anemia. In contrast, 61 patients with acute leukemia before treatment exhibited increased serum ALD-A levels ranging from 125 to 1,550 ng/ml, with a mean value of 480 ng/ml. Serum ALD-A levels in 24 patients with chronic myelocytic leukemia (CML) during the chronic phase also exhibited high mean values of 481 ng/ml in a range of 270 to 1,100 ng/ml. Serum ALD-A levels were higher than 210 ng/ml in 85.2% of the patients with acute leukemia and in all patients with CML. Serum ALD-A levels tended to be decreased within the normal range, if those patients could achieve complete remission. In contrast, serum ALD-A levels showed a tendency to increase if those patients experienced a relapse of leukemia. These results suggest that the measurement of serum ALD-A levels by radioimmunoassay is useful for diagnosis and prediction of relapse in patients with leukemia.
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PMID:[Clinical significance of aldolase A in sera of patients with leukemia]. 143 40

Aldolase A derived from a hemolytic anemia patient with aldolase A deficiency was shown to have an amino acid substitution of glycine for aspartic acid at the 128th position (Asp-128) in the enzyme [Kishi et al. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8623-8627]. We constructed an Escherichia coli expression plasmid, pHAAD128G, which carries the mutant aldolase A [aldolase A(D-G)] cDNA, and the enzyme generated in E. coli transfected with the expression plasmid was purified and characterized. Conversion of Asp to Gly at the 128th position in the enzyme rendered the enzyme thermolabile and susceptible to tryptic digestion. CD spectra analysis also revealed that the mutant enzyme had a remarkable conformation change with a decrease of regular form in the molecule. Addition of glycerol or some other polyalcohols during thermal treatment protected this altered enzyme (but not the normal enzyme) against denaturation and activity decrease. In order to determine the function of the amino acid residue at the 128th position, two artificial mutant enzymes with the substitutions of Glu for Asp [aldolase A(D-E)] and Ser for Asp [aldolase A(D-S)], respectively, at the position were constructed by site-directed mutagenesis and characterized. These analyses demonstrated the necessity for Asp to be present at the 128th residue in order for this enzyme to be thermally stable.
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PMID:Human aldolase A of a hemolytic anemia patient with Asp-128----Gly substitution: characteristics of an enzyme generated in E. coli transfected with the expression plasmid pHAAD128G. 222 18

A radioimmunoassay specific for human aldolase A subunits was used to measure human aldolase A (ALD-A) in human serum. The double antibody competitive inhibition radioimmunoassay technique used radioiodinated purified ALD-A as ligand, chicken antisera specific for human ALD-A and rabbit antichicken IgG. The serum levels of ALD-A in 42 normal healthy subjects ranged from 130 to 210 ng/ml (mean average, 171 +/- 39 ng/ml). In 177 hospitalized patients without cancer, muscle diseases, or hemolytic anemia, the ALD-A serum levels ranged from 125 to 220 ng/ml. In contrast, 82% of 260 patients with various types of malignancy had ALD-A serum concentrations above the normal range. The CEA levels increased only 44% of the sera of 80 patients with cancer of the digestive tract, whereas the ALD-A levels were increased in 86% of the patients. The AFP levels were greater than 100 ng/ml in only 70% of the sera of 33 liver cell carcinoma patients, whereas the ALD-A levels were increased in 94% of these sera. The measurement of serum ALD-A by radioimmunoassay may be a valuable adjunct in the clinical diagnosis of certain cancer patients.
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PMID:Radioimmunoassay of aldolase A. Determination of normal serum levels and increased serum concentration in cancer patients. 618 27

We report the construction of subunit interface mutants of rabbit muscle aldolase A with altered quaternary structure. A mutation has been described that causes nonspherocytic hemolytic anemia and produces a thermolabile aldolase (Kishi H et al., 1987, Proc Natl Acad Sci USA 84:8623-8627). The disease arises from substitution of Gly for Asp-128, a residue at the subunit interface of human aldolase A. To elucidate the role of this residue in the highly homologous rabbit aldolase A, site-directed mutagenesis is used to replace Asp-128 with Gly, Ala, Asn, Gln, or Val. Rabbit aldolase D128G purified from Escherichia coli is found to be similar to human D128G by kinetic analysis, CD, and thermal inactivation assays. All of the mutant rabbit aldolases are similar to the wild-type rabbit enzyme in secondary structure and kinetic properties. In contrast, whereas the wild-type enzyme is a tetramer, chemical crosslinking and gel filtration indicate that a new dimeric species exists for the mutants. In sedimentation velocity experiments, the mutant enzymes as mixtures of dimer and tetramer at 4 degrees C. Sedimentation at 20 degrees C shows that the mutant enzymes are > 99.5% dimeric and, in the presence of substrate, that the dimeric species is active. Differential scanning calorimetry demonstrates that Tm values of the mutant enzymes are decreased by 12 degrees C compared to wild-type enzyme. The results indicate that Asp-128 is important for interface stability and suggest that 1 role of the quaternary structure of aldolase is to provide thermostability.
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PMID:Subunit interface mutants of rabbit muscle aldolase form active dimers. 783

Aldolase (EC 4.1.2.13) plays an important role in glucose metabolism. Aldolase has a molecular weight of 160 kDa and has three isozymes, namely aldolase A, B and C. The enzyme is probably present in all cells; it occurs in particularly large quantities in the muscles, liver and brain. An increase in serum aldolase is found in myotonic muscular disease, such as progressive muscular dystrophy and polymyositis. The enzyme rises in myocardial infarction, reaches a maximum within 24-48 hours and returns to normal in the course of five days. In these muscular diseases, aldolase A isozyme is elevated. Aldolase activity, especially B isozyme, in serum rises to very high levels in acute hepatitis, but is slightly elevated in cirrhosis, chronic hepatitis and obstructive jaundice. Aldolase becomes elevated in serum with malignant tumors, and isozyme A is predominant in serum. Erythrocytes are also rich in aldolase, and the enzyme rises in hemolytic anemia.
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PMID:[Aldolase]. 1179 71

We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) aldolase A gene in a child with suspected haemolytic anaemia associated with myopathic symptoms at birth and with a subsequent diagnosis of arthrogryposis multiplex congenita and pituitary ectopia. Sequence analysis of the whole gene, also performed on the patient's full-length cDNA, revealed only a Gly346-->Ser substitution in the heterozygous state. We expressed in a bacterial system the new aldolase A Gly346-->Ser mutant, and the Glu206-->Lys mutant identified by others, in a patient with an aldolase A deficit. Analysis of their functional profiles showed that the Gly346Ser mutant had the same Km as the wild-type enzyme, but a 4-fold lower kcat. The Glu206-->Lys mutant had a Km approx. 2-fold higher than that of both the Gly346-->Ser mutant and the wild-type enzyme, and a kcat value 40% less than the wild-type. The Gly346-->Ser and wild-type enzymes had the same Tm (melting temperature), which was approx. 6-7 degrees C higher than that of the Glu206-->Lys enzyme. An extensive molecular graphic analysis of the mutated enzymes, using human and rabbit aldolase A crystallographic structures, suggests that the Glu206-->Lys mutation destabilizes the aldolase A tetramer at the subunit interface, and highlights the fact that the glycine-to-serine substitution at position 346 limits the flexibility of the C-terminal region. These results also provide the first evidence that Gly346 is crucial for the correct conformation and function of aldolase A, because it governs the entry/release of the substrates into/from the enzyme cleft, and/or allows important C-terminal residues to approach the active site.
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PMID:Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function. 1476 13

Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease.
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PMID:A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. 2539 8