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

The effects of a chronic 8- to 12-week administration of the hepatic tumor promoter, phenobarbital, on further altering the biochemical enzyme deviation patterns shown by hyperplastic liver nodules was examined in rats previously subjected to the initiation/selection protocol of Solt and Farber. Hyperplastic liver nodules of various size classes from the phenobarbital-treated group exhibited a significant increase in GGT specific activity, as well as 2- to 3-fold higher levels of microsomal cytochrome P-450 than was shown by control nodules. The increase in GGT specific activity was also found in many cases to be higher in those hyperplastic liver nodules from the phenobarbital-treated group with diameters greater than 3.0-3.5 mm than in nodules of a smaller size. In contrast, the GGT specific activity of the control nodules did not correlate with differences in their sizes. Furthermore, while histochemical staining of GGT activity appeared uniform in sections of the various sized hyperplastic nodules from the phenobarbital-treated group, biochemical measurements indicated a consistently higher specific activity for this enzyme in tissue taken from the central portion of the nodule than in tissue from the peripheral portion of the nodule. On the other hand, the specific activities of glucose-6-phosphatase, 5'-nucleotidase, and fructose-1,6-diphosphate aldolase of the hyperplastic liver nodules were not found to be significantly altered over control values by the chronic phenobarbital treatment, suggesting a stability of these other marker enzyme alterations during the early promotional phase of hepatocarcinogenesis.
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PMID:Effect of phenobarbital on the altered biochemical phenotypes expressed by hyperplastic liver nodules during hepatocarcinogenesis in the rat. 614 62

Free ribosomes and membrane-bound ribosomes were prepared from rat livers, and the contributions of these two types of ribosomes to the synthesis of aldolase B were studied by the immunoprecipitation of [3H]puromycin-labeled nascent peptides with a rabbit antibody to this enzyme. Although rat liver aldolase was recovered in both cytosolic and microsomal fractions by the fractionation of liver homogenate, the microsomal aldolase was immunologically identical with its cytosolic counterpart as confirmed by Ouchterlony immunodiffusion test. We examined the nascent peptide fractions prepared from free and bound ribosomes, and found that the nascent peptides of aldolase were mainly localized in free ribosomes. About 0.5% of the total nascent peptides of free ribosomes and 0.08% of those of bound ribosomes was aldolase. The site of synthesis of serum albumin was also examined as a reference standard by the immunoprecipitation of labeled nascent peptides, and the nascent peptides of this secretory protein were mainly associated with bound ribosomes, as reported by other workers. These observations confirm that aldolase B is mainly synthesized by free ribosomes in rat liver cells.
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PMID:Biosynthesis of aldolase B by free ribosomes in rat liver. 677 69

To identify possible molecular targets in moderate heat-induced, short-term derangements of rat testicular endocrine function, rates of androgen and precursor biosynthesis and key enzyme concentrations were compared at 38 degrees C (normal body core temperature) and 31 degrees C (normal scrotal temperature) in three in-vitro models of decreasing complexity and increasing specificity. In purified Leydig cells and similarly in decapsulated testes, gross testosterone secretion was by 20% higher at 38 degrees C under basal conditions and during the initial phase of stimulation with hCG or cAMP; longer (> 1 hour) exposure to the elevated temperature resulted in a marked decrease (52% after 3 hours) of testosterone response to hCG or cAMP as compared to the corresponding rates at 31 degrees C. This phenomenon was neither due to the development of hormone resistance at the receptor level nor to restricted cholesterol supply and turnover nor to increased testosterone accumulation. Whereas mitochondrial CYP11A (cytochrome P450cscc: cholesterol monooxygenase) was absolutely temperature-insensitive in all systems tested, CYP17 (cytochrome P450c17: steroid-17 alpha-monooxygenase/C17, 20-aldolase) in the smooth endoplasmic reticulum responded with a 57% loss in whole testes and 39% loss in purified Leydig cells upon a 3-hour temperature elevation from 31 degrees C to 38 degrees C. In contrast, CYP17 was stable (4% loss) when tested directly in microsomal membranes. It is concluded that CYP17, but not CYP11A, is very sensitive towards even moderate elevation of environmental temperature, and that this apparent lability is not an intrinsic property of the enzyme protein but rather mediated by heat-activated intracellular factors.
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PMID:Rapid down-regulation of testicular androgen biosynthesis at increased environmental temperature is due to cytochrome P450c17 (CYP17) thermolability in Leydig cells, but not in endoplasmic reticulum membranes. 881 42

This study uses microsomal membranes from rat testis tissue, including the cytochrome P450c17 (steroid 17 alpha-monooxygenase/17 alpha-hydroxyprogesterone aldolase, catalyzing the conversion of progesterone to androstenedione), to decipher the possible relation of NADPH-induced (no exogenous iron added) lipid peroxidation and cytochrome P450 inactivation and the protective effect of certain steroids. NADPH (300 microM) causes a 3.6-fold stimulation of malondialdehyde formation (thiobarbituric acid-reactive substances) and a 29% cytochrome P450c17 loss within 1 h at 37 degrees C, but has no effect on lipid peroxidation in the presence of the iron chelator desferrioxamine. Hydrogen peroxide has only marginal effects. The antioxidant efficiency of estradiol (IC50 = 13.9 microM) is higher than its cytochrome P450c17 protective efficiency (IC50 = 33.0 microM), whereas androstenedione does not inhibit lipid peroxidation but protects cytochrome P450c17 completely. The human choriogonadotropin-induced degradation of cytochrome P450c17 in incubated decapsulated testes can not be correlated with a stimulation of lipid peroxidation, and it is partially inhibited by estradiol but completely abolished by androstenedione. It is concluded (I) that NADPH stimulates iron-dependent generation of reactive oxygen species by the monooxygenase system even in the presence of certain P450 ligands in the physiological membrane environment, (II) that membrane lipid peroxidation may be suppressed by hydrophobic steroids acting as antioxidants such as estradiol, (III) that steroid ligands stabilize cytochrome P450c17 against inactivation in the presence of NADPH even if they do not act as substrates and do not possess antioxidant activity, and (IV) that the choriogonadotropin-induced down-regulation of cytochrome P450c17 is not due to accumulating steroids acting as "pseudosubstrates" as occasionally supposed.
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PMID:Novel connections between NADPH-induced lipid peroxidation and cytochrome P450 inactivation, and antioxidant and enzyme protective properties of estradiol in gonadal membranes. 925 24

Spatial and temporal distribution of the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (pfGAPDH) and aldolase (pfAldolase) of Plasmodium falciparum were investigated using specific mAbs and indirect immunofluorescence analysis (IFA). Both glycolytic enzymes were co-localized during ring and trophozoite stages of both liver and asexual blood stage parasites. During schizogony, pfGAPDH became associated with the periphery of the parasites and eventually accumulated in the apical region of merozoites, while pfAldolase showed no segregation. Subcellular fractionation experiments demonstrated that pfGAPDH was found in both the membrane-containing pellet and the supernatant fraction of parasite lysates. In contrast, pfAldolase was only found in the supernatant fraction. A quantitative binding assay showed that pfGAPDH could be recruited to HeLa cell microsomal membranes in response to mammalian GTPase Rab2, indicating that Rab2-dependent recruitment of cytosolic components to membranes is conserved in evolution. Two overlapping fragments of pfGAPDH (residues 1-192 and 133-337) were evaluated in the microsomal binding assay. We found that the N'-terminal fragment competitively inhibited Rab2-stimulated pfGAPDH recruitment. Thus, the domain mediating the evolutionarily conserved Rab2-dependent membrane recruitment is located in the N'-terminus of GAPDH. Together, these results suggest that pfGAPDH exerts non-glycolytic function(s) in P. falciparum, possibly including a role in vesicular transport and biogenesis of apical organelles.
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PMID:The N'-terminal domain of glyceraldehyde-3-phosphate dehydrogenase of the apicomplexan Plasmodium falciparum mediates GTPase Rab2-dependent recruitment to membranes. 1297 91

Recent observations have suggested that Ras signaling includes combinations of extracellular-signal-regulated Ras activation at the plasma membrane and endomembranes, and translocation of Ras from the plasma membrane to intracellular compartments. In this study we have shown that social isolation of rat decreases the content of Bcl-2-associated K-Ras in hippocampal mitochondria, whereas the amount of H-Ras is increased in the microsomal fraction. Furthermore, we have found that galectin 1, a binding partner of activated Ras, was increased in the soluble fractions. The redistribution of Ras isoforms was accompanied by acceleration in mitochondrial hexokinase and inhibition of mitochondrial aconitase, succinate dehydrogenase, and creatine kinase, whereas the activity of aldolase, as well as cytoplasmic creatine kinase was not changed. Our data suggest that inhibition of mitochondrial oxidative metabolism by reactive oxygen species (ROS) and compensatory elevation of glycolysis in hippocampus occurs during social isolation of rats and Ras trafficking could play an important role in switching of impaired oxidative phosphorylation to anaerobic glycolysis.
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PMID:Social isolation in rats inhibits oxidative metabolism, decreases the content of mitochondrial K-Ras and activates mitochondrial hexokinase. 1961 40


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