Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.1.2.13 (aldolase)
3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in blood-level of cadmium, zinc, pseudocholinesterase and aldolase were studied in 44 normal subjects, 40 hypertensive patients and 40 alcoholic ones. The highest serum concentration of cadmium and pseudocholinesterase, the lowest serum and blood concentrations of zinc, the lowest serum concentrations of aldolase were found in the two groups of patients, with still lower levels in alcoholic patients than in hypertensive ones. There was a negative correlation between zinc and cadmium levels in the three groups of subjects. There was a high correlation between systolic and diastolic blood pressure value and cadmium, and negative correlation between blood pressure and zinc blood and serum levels.
...
PMID:[Cadmium, zinc, pseudo-cholinesterase and aldolase blood levels in hypertensive and alcoholic patients. Preliminary statistical computerised study on 124 cases (author's transl)]. 625 98

The infrared spectrum of the complex of D-fructose 1,6-bisphosphate bound to yeast aldolase displays three spectral features between 1700 and 1800 cm-1. One of these (at 1730 cm-1) corresponds to the carbonyl group of enzyme-bound D-fructose 1,6-bisphosphate and/or dihydroxyacetone phosphate. The frequency of this band, which is unaffected by the removal of the intrinsic zinc ion from the enzyme, demonstrates that this carbonyl group is not significantly polarized when the substrate binds to the enzyme. In contrast, the spectral band assigned to the carbonyl group of enzyme-bound D-glyceraldehyde 3-phosphate (at 1706 cm-1) appears at a frequency 24 cm-1 lower than when this substrate is in aqueous solution. This shift indicates considerable polarization of the carbonyl group when D-glyceraldehyde 3-phosphate is bound at the active site. The third spectral feature (at 1748 cm-1), which is observed only in the presence of potassium ion, probably corresponds to an enzymic carboxyl group in a nonpolar environment.
...
PMID:Polarization of substrate carbonyl groups by yeast aldolase: investigation by Fourier transform infrared spectroscopy. 633 12

A pathway from glucose via sorbitol bypasses the control points of hexokinase and phosphofructokinase in glucose metabolism. It also may produce glycerol, linking the bypass to lipid synthesis. Utilization of this bypass is favored by a plentiful supply of glucose--hence, conditions under which glycolysis also is active. The bypass further involves oxidation of NADPH, so the pentose phosphate pathway and the bypass are mutually facilitative. Possible consequences in different organs under normal and pathological, especially diabetic, conditions are detailed. Enzymes with related structures (for example, sorbitol dehydrogenase and alcohol dehydrogenase, and possibly, aldehyde reductase and aldose reductase, respectively) are linked functionally by this scheme. Some enzymes of the bypass also feature in glycolysis (aldolase and alcohol dehydrogenase), and these enzymes, with the reductases involved, are proteins known to occur in different classes or multiple isozyme forms. Two of the enzymes (aldolase and alcohol dehydrogenase) both involve classes with and without a catalytic metal (zinc). The existence of parallel pathways and the occurrence of similar enzymic steps in one pathway may help to explain the abundance and multiplicity of enzymes such as reductases, aldolases, and alcohol dehydrogenases.
...
PMID:Enzyme relationships in a sorbitol pathway that bypasses glycolysis and pentose phosphates in glucose metabolism. 640 81

The in vivo effects of zinc (Zn) and manganese (Mn) on the activity of delta-aminolevulinic acid dehydratase (5-aminolevulinate hydrolyase, ALAD, EC 4.2.1.24) in blood with and without inhibition by lead and on the functions of the liver and kidney were studied in rabbits. Administration of Zn or Mn alone caused little change in any of the 29 parameters tested at concentrations of 5, 10, 25 or 50 mumol element/kg body weight. Administration of 5 mumol lead/kg inhibited ALAD activity in blood, but it did not induce any marked effects on the indices of hepatic and renal functions. In simultaneous i.v. injection with lead and manganese, both at a dose of 5 mumol/kg, however, the recovery process of ALAD activity was delayed. Three out of 29 parameters tested, beta-lipoprotein, triglyceride and aldolase, increased significantly one day after simultaneous injection with lead and manganese. Equimolar zinc did not show either an antagonistic or cooperative effect on these three parameters and the ALAD activity in blood.
...
PMID:The in vivo effects of manganese and zinc on delta-aminolevulinic acid dehydratase activity inhibited by lead. 669 5

The ability of rat liver zinc-thionein to donate its metal to the apo-enzymes of the zinc enzymes horse liver alcohol dehydrogenase, yeast aldolase, thermolysin, Escherichia coli alkaline phosphatase and bovine erythrocyte carbonic anhydrase was investigated. Zinc-thionein was as good as, or better than, ZnSO(4), Zn(CH(3)CO(2))(2) or Zn(NO(3))(2) in donating its zinc to these apo-enzymes. Apo-(alcohol dehydrogenase) could not be reactivated by zinc salts or by zinc-thionein. Incubation of the other apo-enzymes with near-saturating amounts of zinc as ZnSO(4), Zn(CH(3)CO(2))(2), Zn(NO(3))(2), or zinc-thionein resulted in reactivation of the apo-enzymes. With apo-aldolase zinc-thionein gave 100% reactivation within 30min. Reactivation by ZnSO(4) and Zn(CH(3)CO(2))(2) was complete and instantaneous. Zinc-thionein was somewhat better than Zn(NO(3))(2) in completely reactivating apo-thermolysin. With apo-(alkaline phosphatase) 43% reactivation was obtained with Zn(CH(3)CO(2))(2) and 18% with zinc-thionein. With apo-(carbonic anhydrase) zinc-thionein was better than ZnSO(4), Zn(CH(3)CO(2))(2) or Zn(NO(3))(2), with a maximal reactivation of 54%. That zinc was really being transferred from zinc-thionein to apo-(carbonic anhydrase) was shown by the fact that 2,6-pyridine dicarboxylic acid and 1,10-phenanthroline had minimal effects on the reactivation of apo-(carbonic anhydrase) when added after the incubation {[apo-(carbonic anhydrase)+zinc thionein]+chelator}, but inhibited reactivation when added before the incubation {apo-(carbonic anhydrase)+[zinc-thionein+chelator]}. These observations support the idea that zinc-thionein can function in zinc homeostasis as a reservoir of zinc, releasing the metal to zinc-requiring metalloenzymes according to need.
...
PMID:Reactivation in vitro of zinc-requiring apo-enzymes by rat liver zinc-thionein. 677 58

A class II Zn(2+)-dependent fructose-1,6-bisphosphate (FBP)- aldolase was purified from an overproducer strain of Escherichia coli and characterized by standard biochemical techniques and 13C NMR spectroscopy. The principal finding of these studies was identification, by 13C NMR spectroscopy, of an enzyme-bound reaction intermediate, the enediol(ate) form of dihydroxyacetone phosphate (DHAP). Formation of this intermediate requires the presence of Zn2+ and is pH dependent, with increasing amounts of this tautomer appearing at alkaline pH's. This pH dependence closely parallels the pH activity profile of the enzyme, suggesting an involvement of the enediol-DHAP form in the reaction pathway. In addition to these results the following observations were made on this enzyme: (a) E. coli FBP aldolase binds and utilizes only the carbonyl forms of FBP and DHAP; (b) the function of Zn2+ in this metalloaldolase appears to be polarization of the C = O bond of DHAP; (c) activity of this enzyme is unaffected by glycolytic intermediates or nucleotide phosphates such as ATP. Although these studies provide some information about the catalytic mechanism of E. coli FBP aldolase, they do not provide an explanation for the apparent regulation of this enzyme reported in previous in vivo NMR studies. While the possibility that the enzyme is allosterically regulated cannot be excluded at this time, an interesting possibility suggested by this and other studies is that in E. coli glycolytic substrates may be channeled through a multienzyme complex.
...
PMID:Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis. 787 90

A Ni(2+)-binding protein (pNiXc, 40 kDa), present in Xenopus laevis oocytes and embryos, was isolated from mature oocytes by chromatography on DEAE-cellulose and cellulose phosphate, followed by FPLC on Ni-iminodiacetate-Agarose, or reverse-phase HPLC on a C-4 column. Size-exclusion HPLC showed that intact pNiXc is approximately 155 kDa, consistent with tetrameric structure. After cleavage with Lys-C proteinase or cyanogen bromide, six peptides were separated by HPLC and sequenced by Edman degradation, providing sequence data for 83 residues. Data-base search showed similarity of pNiXc to eukaryotic aldolases, with 96% identity to human aldolase A. pNiXc demonstrated aldolase activity with fructose 1,6-bisphosphate as substrate (Km, 30 microM Vmax 26 mumol min-1 mg-1); the aldolase activity was inhibited non-competitively by Cu2+, Cd2+, Co2+, or Ni2+. Equilibrium dialysis showed high affinity binding (Kd, 7 microM) of 1 mole of Ni per mole of 40 kDa subunit. Based on metal-blot competition assays, the abilities of metals to compete with 63Ni2+ for binding to pNiXc were ranked: Cu2+ >> Zn2+ > Cd2+ > Co2+. This study identifies pNiXc as the monomer of fructose-1,6-bisphosphate aldolase A, and raises the possibility that aldolase A is a target enzyme for metal toxicity.
...
PMID:The 40 kDa 63Ni(2+)-binding protein (pNiXc) on western blots of Xenopus laevis oocytes and embryos is the monomer of fructose-1,6-bisphosphate aldolase A. 787 95

An expression and mutagenesis system for the E. coli Class II fructose-1,6-bisphosphate aldolase has been created by modification of the vector pKfda (Biochem. J. 257 (1989) 529-534). Large amounts of Class II aldolase (about 1 g/l in crude extracts), with properties consistent with those previously reported for the naturally occurring enzyme (Biochem. J. 169 (1978) 633-641) are obtained. The enzyme contains 2 zinc ions per enzyme dimer. We have investigated the nature of the zinc-binding site of the enzyme by site-directed mutagenesis. His-108, His-111, Cys-112 and His-142 were identified as possible zinc-binding ligands by sequence alignments and comparisons with other known zinc-containing enzymes. Mutation of these residues identified His-108 and His-111 as two of the ligands directly responsible for the tight binding of zinc. Mutation of the other two residues results in only a small effect on the amount of zinc bound per monomer and a corresponding change in specific activity. These residues are, therefore, unlikely to be directly involved in zinc binding, but may be indirectly involved in some manner in the zinc-binding environment.
...
PMID:Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli. 843 19

The three-dimensional structure of L-fuculose-1-phosphate aldolase (FucA) from Escherichia coli was determined by X-ray crystallography at a resolution of 2.13 A. The enzyme is a homotetramer with an M(r) of 23,775 per subunit. Since its activity depends on the presence of metal ions (Zn2+) the enzyme belongs to the class II aldolases. As expected from amino acid sequence comparisons, this first structure of a class II aldolase shows no similarity to the known structures of class I aldolases. It has some unusual features concerning the overall chain fold, the quaternary structure, and the co-ordination of the catalytically active zinc ion. A sequence comparison with the data bank indicated that the middle domain of the enzyme L-ribulose-5-phosphate-4-epimerase is homologous to FucA and may contain an active-center metal ion.
...
PMID:The spatial structure of the class II L-fuculose-1-phosphate aldolase from Escherichia coli. 851 38

The structure of L-fuculose-1-phosphate aldolase in a cubic crystal form has been determined with and without the inhibitor phosphoglycolohydroxamate at 2.4 and 2.7 angstrom (1 angstrom = 0.1 nm) resolution, respectively. This inhibitor mimics the enediolate transition state of the substrate moiety dihydroxyacetone phosphate. The structures showed that dihydroxyacetone phosphate ligates the zinc ion of this metal-dependent class II aldolase with its hydroxyl and keto oxygen atoms, shifting Glu73 away from the zinc coordination sphere to a non-polar environment. At this position Glu73 accepts a proton in the initial reaction step, producing the enediolate which is then stabilized by the zinc ion. The other substrate moiety L-lactaldehyde was modeled, because no binding structure is yet available.
...
PMID:Catalytic mechanism of the metal-dependent fuculose aldolase from Escherichia coli as derived from the structure. 867 81


<< Previous 1 2 3 4 5 6 7 Next >>

---