Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood DNA was hybridized to the full-length cDNA and the cloned structural gene of human aldolase B. With PvuII endonuclease a restriction fragment length polymorphism was detected that was present in the heterozygous state in about 21% of the individuals tested. A map of the human aldolase gene was constructed for the two groups of individuals found to produce different fragments after PvuII digestion. This allowed the localization of the polymorphic site within the gene, which was found to be due to the loss of a PvuII site in the last intron upstream from the 3' end. This polymorphism may be used as a genetic marker to study individuals affected by hereditary fructose intolerance.
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PMID:Mapping of a restriction fragment length polymorphism within the human aldolase B gene. 288 17

Vertebrates possess three isozyme forms of fructose diphosphate aldolase. We have isolated two overlapping chicken genomic clones which encode the liver-specific form of this enzyme; we have identified the 5' and 3' ends of this gene by a combination of primer extension analysis and S1 mapping; and we have determined the entire nucleotide sequence of this gene including 1400 base pairs (bp) of sequence from the regions flanking the 5' and 3' ends of the gene. The transcriptional unit for the aldolase B gene spans 8700 bp and contains eight intervening sequences, including a 4600-bp intron in the 5' non-coding region. On the basis of results from Southern genomic hybridizations, the aldolase B gene appears to be present only once per haploid genome. No differences were detected in the mRNA structure between RNA from three tissues expressing aldolase B (liver, kidney, and small intestine). Various features of the 5' flanking region are discussed, including a partial homology with the 5' noncoding region from rabbit aldolase A.
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PMID:Characterization of the chicken aldolase B gene. 298 60

We used a cloned cDNA probe for the B subunit of human aldolase (ALDB) and Southern blotting techniques to analyse DNA from a series of rodent X human somatic cell hybrids for the presence of specific ALDB-related sequences. Our results provide evidence for the assignment of the gene for ALDB to chromosome 9. Moreover, by direct gene dosage determination in two patients with chromosome 9 unbalanced rearrangements and by in situ hybridization we refined the regional chromosomal assignment to 9q13----q32 and most probably to 9q21.3----9q22.2.
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PMID:The structural gene for aldolase B (ALDB) maps to 9q13----32. 300 Feb 75

DNA methylation was studied as a potential factor for the regulation of tissue-specific and developmentally specific expression of the rat aldolase B gene. We examined cytosine methylation in the HpaII and HhaI recognition sequences in the aldolase B gene in aldolase expressing and nonexpressing tissues and cells. Out of the 15 methyl-sensitive restriction sites examined, the sites in the 3'-half and 3'-flanking regions were found to be heavily methylated in all the tissues or cells, regardless of the level of aldolase B gene expression. However, the methylation pattern in the region immediately upstream and in the 5'-half of the gene exhibited tissue-specificity: the site located about 0.13 kb upstream of the cap site (just next to the CCAAT box), and the sites in the first intron (intron 1) were heavily methylated in nonexpressing cells and tissues (ascites hepatoma AH130 and brain), whereas those in an expressing tissue (liver) were considerably less methylated. These results suggest that cytosine methylation at the specific sites in the 5'-flanking and 5'-half regions of the gene is associated with repression of the gene activity. However, the gene is still substantially methylated in the fetal liver on day 16 of gestation, when it is in a committed state for rapid activation in the period immediately afterwards (Numazaki et al. (1984) Eur. J. Biochem. 152, 165-170). This suggests that demethylation of the methylated cytosine residues in the specific gene region is not necessarily required before activation of the gene during development, but it may occur along with or after the activation.
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PMID:DNA methylation and the regulation of aldolase B gene expression. 302 54

The complete protein sequence of the human aldolase C isozyme has been determined from recombinant genomic clones. A genomic fragment of 6673 base pairs was isolated and the DNA sequence determined. Aldolase protein sequences, being highly conserved, allowed the derivation of the sequence of this isozyme by comparison of open reading frames in the genomic DNA to the protein sequence of other human aldolase enzymes. The protein sequence of the third aldolase isozyme found in vertebrates, aldolase C, completes the primary structural determination for this family of isozymes. Overall, the aldolase C isozyme shared 81% amino acid homology with aldolase A and 70% homology with aldolase B. The comparisons with other aldolase isozymes revealed several aldolase C-specific residues which could be involved in its function in the brain. The data indicated that the gene structure of aldolase C is the same as other aldolase genes in birds and mammals, having nine exons separated by eight introns, all in precisely the same positions, only the intron sizes being different. Eight of these exons contain the protein coding region comprised of 363 amino acids. The entire gene is approximately 4 kilobases.
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PMID:The complete amino acid sequence of the human aldolase C isozyme derived from genomic clones. 310 2

Serum aldolase B levels were determined in patients with malignant tumors using a radioimmunoassay method. Thirty-one of 52 patients with malignant tumors had decreased serum aldolase B levels of less than 20 ng/ml, whereas almost all of the normal subjects and the patients with liver diseases and other benign diseases showed serum aldolase B levels of more than 20 ng/ml. The decreased aldolase B levels observed in cancer patients were unrelated to the clinical stage of their disease. The decrease of aldolase B correlated well with the decrease of fructose-1-phosphate (F1P)-aldolase activity, but not with fructose-1,6-diphosphate (FDP)-aldolase activity in the sera of cancer patients. Mixing experiments did not identify an inhibitor of aldolase B in sera of cancer patients. Furthermore, recovery of serum aldolase B levels after successful surgical resection in cancer patients suggested that the low levels of aldolase B in sera of cancer patients was not of genetic origin. The mechanism responsible for the decrease of aldolase B in sera of cancer patients is unclear.
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PMID:Decreased serum aldolase B levels in patients with malignant tumors. 319 54

A search for target proteins of inositol polyphosphates in mammalian tissues revealed that fructose 1,6-bisphosphate aldolases are potent isomer-selective binders of inositol polyphosphates. Binding was measured by tryptophan fluorescence quenching, by difference spectroscopy, and, in aldolase A, by equilibrium dialysis. Among a series of inositol phosphates containing between one and six phosphates and varying in their positions, inositol 1,4,5-trisphosphate was found to be bound strongest both by aldolase A [( L]0.5 = 0.58 microM) and aldolase B [( L]0.5 = 0.83 microM). Aldolase A showed also a strong binding of inositol tetrakisphosphate [( L]0.5 = 0.83 microM), of inositol 2,4,5-trisphosphate [( L]0.5 = 1.4 microM) and of inositol 1,3,4,5,6-pentakisphosphate [( L]0.5 = 2.0 microM); in aldolase B but not in aldolase A inositol 4,5-bisphosphate was bound as strongly as inositol 1,4,5-trisphosphate [( L]0.5 = 0.95 microM) and also inositol 2,4,5-trisphosphate was tightly bound [( L]0.5 = 1.2 microM). Both in aldolase A and B, 4 mol inositol 1,4,5-trisphosphate were bound/mol tetramer, in aldolase A a total binding of 8 mol inositol 1,4-bisphosphate/mol tetramer was evaluated. Difference spectra revealed that the binding of inositol phosphates to both isoenzymes may be associated with conformational changes. The binding of all inositol phosphates led to an inhibition of the enzyme activity. In aldolase A the inhibition was purely competitive, in aldolase B a complex cooperative type of inhibition was evident with fructose 1,6-bisphosphate as a substrate whereas with fructose 1-phosphate the inhibition also was purely competitive. Model calculations based on the in vitro data indicated a significant potential of aldolase to bind preferentially inositol 1,4,5-trisphosphate also in the presence of excess fructose 1,6-bisphosphate.
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PMID:Mammalian aldolases are isomer-selective high-affinity inositol polyphosphate binders. 378 Jul 51

Rabbit liver aldolase B (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) contains 8 SH groups/subunit and no disulfide bonds. In the native enzyme 3 SH groups/subunit are titrable with 5,5'-dithiobis(2-nitrobenzoic) acid (Nbs2), 2,2'-dithiodipyridine and N-ethylmaleimide, whereas p-mercuribenzoate is able to react with 4 thiol groups per subunit. Among the three thiol groups titrable with Nbs2, two react 'fast' with simple second-order kinetics, one reacts 'slow' and for this thiol group saturation kinetics is observed, suggesting a reversible binding of Nbs2 to the enzyme prior to covalent modification. It is shown that this binding most likely occurs via ionic interactions in the region close to the active site. The kinetic differentiation between the two 'fast' reacting groups is possible by kinetic analysis of the release of Nbs residues from the modified enzyme. Modification of all exposed SH groups of aldolase B results in 14-32% loss of enzymatic activity. The complete inactivation of liver aldolase by 1 mM p-mercuribenzoate reported previously (Waud, J.M., Feldman, E. and Schray, K.J. (1981) Arch. Biochem. Biophys. 206, 292-295) is shown to be caused by a nonspecific reaction of this reagent used in large excess. It is concluded that this isoenzyme differs from muscle aldolase in the reactivity of exposed SH groups, the mechanisms of the interaction with modifying agents and also in the effect of SH group modification on the enzymatic activity.
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PMID:The reactivity and function of cysteine residues in rabbit liver aldolase B. 379 May 75

A human hybridoma clone (4E3) has been established by fusing lymphocytes from a lymph node taken from a breast cancer patient and human lymphoblastoid cells, LICR-LON-HMy2, by the poly(ethylene glycol) method. 4E3 has been stabilized and continued to secrete IgMk antibody into culture medium (greater than 10 micrograms/ml) for over 1 year. The following characteristics of the antigen strongly suggested that 4E3 recognizes liver-type aldolase B (EC 4.1.2.13): the Mr of the native molecule is 160,000 and that of the subunit is 40,000, and thus it has a tetrameric structure of identical subunits; the antigen is abundant in the liver and kidney of human, mouse and rabbit, and is localized by immunohistochemical methods in the cytoplasm of hepatocytes and in the proximal tubules of the kidney; the antigen is precipitable by 50-80% saturation with (NH4)2SO4; the antigen shows charge-dependent heterogeneity on DEAE-cellulose chromatography. To confirm this notion, aldolase B was purified to homogeneity from the liver of human, mouse and rabbit by phosphocellulose chromatography. During the chromatographic purification, the antigen activity as assayed by enzyme-linked immunosorbent assay (e.l.i.s.a.) was superimposed on the enzymic activity of aldolase. Furthermore, monoclonal antibody 4E3 strongly reacted with purified aldolase B in SDS/polyacrylamide-gel electrophoresis followed by Western blotting and also in e.l.i.s.a. using microplates coated with purified enzyme. The reaction between aldolase B and 4E3 activated the human complement system as assessed by the attachment of C3 to the immune complex of aldolase B and 4E3.
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PMID:Human monoclonal antibody recognizing liver-type aldolase B. 382 73

Fructose intolerance is caused by a deficit of the liver aldolase B enzyme. Its molecular mechanisms were studied at different sites: The protein was studied by a method combining electrophoresis, transfer and immunology. It was present in the 15 cases examined. The genetic variability was demonstrated by the quantitative differences of the immunoreactive proteins. Aldolase messenger RNA was prepared and used to direct in vitro synthesis of human aldolase. Cloning complementary DNA of human aldolase was achieved by using the messenger RNA. Two clones were prepared. The aldolase B gene was then analysed using restriction enzymes in 60 control subjects and 11 patients. An abnormality of the DNA was demonstrated in one of the patients and in her father.
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PMID:[Study of hereditary fructose intolerance by methods of molecular biology]. 384 Dec 65


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