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 resurgence of aldolase isozymes in cancerous tissues is a well-known but poorly understood phenomenon. This resurgence poses the problem of whether or not adult and fetal aldolase isozymes are produced by the same cells. For clarification of this question, the immunoperoxidase technique was used to locate aldolases A, B, and C in one type of fast-growing hepatoma, the LF hepatoma and, by comparison, in normal adult liver. Under optical microscopy, aldolases A and C were located in the cytoplasm of almost all of the cancerous cells. An isozyme antigenically identical with aldolase B was also demonstrated to be present in almost all of the cells, but the reaction indicating the presence of this isozyme was weaker. In normal adult liver, only aldolases A and B were demonstrated to be present in almost all the hepatocytes. Under electron microscopy in LF hepatoma, the three isozymes were found to be present mainly in the cytoplasm. These facts suggest that the three types of aldolase are very probably present in the same cells at the same time, and they provide indirect arguments leading us to think that the resurgence of fetal aldolase isozymes in cancer is not the consequence of cellular selection but is due to a disturbance at the gene control level.
 ...
PMID:Location of adult and fetal aldolases A, B, and C by immunoperoxidase technique in LF fast-growing rat hepatomas. 20 71

The aldolase activity was measured using two substrates fructose-I-phosphate (FIP) and fructose-1,6-diphosphate (FDP) in the supernatant fraction of homogenates of different mice organs (liver, muscle, brain) and hepatoma tissues during growth of hepatoma 22a. Kinetic parameters Km and Vmax were calsulated. The most essential changes in the activity of aldolase were found during the latent and terminal stares of the hepatoma development. The changes in the aldolase activity observed during development of hepatoma 22a were characterized by altered substrate specificity VFDP /VFIP activity gatio). This ratio was not changed distinctly in liver tissue; in muscles the value decreased from 50 (tumor-free control) to 15 during terminal stages; in brain, to the contrary, it was increased from 20 to 50. The values of Km, Vmax and VFDP /VFIP were similar both in the hepatoma at the eleventh day and in normal brain tissue. The specific inhibition of FDP aldolase activity by ATP was found. Substitution of aldolase B by aldolase AC apparantly ossurred in hepatoma 22a. The data obtained suggest that alteration in the parameters studied may be due to variation in the ration of isozymes.
 ...
PMID:[Change in aldolase activity in the organs of mice in the process of hepatoma 22a development]. 49 46

The process of enzymatic aging was studied in livers of adult and senescent rats for aldolase B. No "cross-reacting material" was found in livers of 27 to 30-month-old rats, estimated by the ratio aldolase activity-antigen amount. The activity towards the two substrates of aldolase, fructose 1,6-diphosphate and fructose 1-phosphate did not vary in senescent animals. Moreover, other physico-chemical properties of the enzyme such as thermal inactivation, immunological reactivity and Michaelis constant remain unchanged. These results provide arguments against the occurrence of errors in protein synthesis as a cause of aging.
 ...
PMID:Aldolase B in the liver of senescent rats. 82 40

Aldolases A, B and C were determined by immunotitration analysis in extracts of human kidney and small intestine and demonstrated immunohistochemically in tissue sections of the same organs at various stages of development. By both techniques a change of isoenzyme pattern during development of the kidney and the small intestine was observed, leading from the predominance of A-type towards the predominance of B-type aldolase. In the extracts of kidney and small intestine the specific activity of aldolase B--but not that of aldolase A--rises with age by about one order of magnitude. The histochemical investigation showed that the developmental change in aldolase pattern in the organ extracts is caused by the differentiation of proximal tubulus cells in the kidney and the differentiation of epithelial cells in the small intestine. Within these cells an increase in the concentration of aldolase B and a decrease in that of aldolase A takes place during development. The possible physiological role of this cellular change in aldolase isoenzyme pattern is discussed. Aldolase C was found only in low concentrations in fetal organs. Only in the kidney, a specific localization within the proximal tubules could be demonstrated.
 ...
PMID:The changes in aldolase isoenzyme pattern during development of the human kidney and small intestine--demonstrated in organ extracts and tissue sections. 84 1

Three aldolase isoenzymes; aldolase A, B and C were found in various human tissues including gastric mucosa, by means of substrate specificities (the fuctose-1, 6-diphosphate aldolase/fructose-1-phosphate aldolase activity ratio) and electrophoresis. The basic pattern of aldolase isoenzyme in man consisted of nine active bands, which were designated as I, II, III, IV, V, VI, VII, VIII and IX band from anode side respectively. The I band corresponded to aldolase C, V to aldolase A and IX to aldolase B. The II, III and IV band are hybrid molecules composed of subunit of aldolase A and C, and the VI, VII and VIII of subunit of aldolase A and B. The V band was present in all tissues, while IX was detected in the liver, kidney and stomach. The I, II, III and IV band were found in all tissues except for muscle. These findings were extremely different from those in other species. In normal gastric mucosa, active bands were composed of I, II, III, IV, V, VIII and IX band, while in gastric cancerous tissue, I, II, III, VIII and IX band were absent or markedly decreased in activity. In contrast, the V band increased. In fetal gastric mucosa, they showed the same pattern as cancerous. In extract of cancerous tissues, the FDP/F1P activity ratio was 20.5+/-2.2, as compared with 7.2+/-0.1 in normal gastric mucosa. In serum of patients with gastric cancer, the FDP/F1P activity ratio was 9.7+/-1.2, while it was 2.9+/-0.4 in normal human serum. These results suggest that the elevation in serum of the FDP/F1P ratio in gastric cancer is due to increase in muscle type isoenzyme (aldolase A) which is derived from cancerous tissue. Furthermore, the analysis of serum aldolase isoenzyme will save for cancer diagnosis.
 ...
PMID:[The distribution of the aldolase isoenzymes in various human tissues and the anomaly in cancerous tissues -especially in gastric cancer- (author's transl)]. 124 Aug 53

The aldolase isozyme family is composed of three members, A, B, and C, which are encoded by separate genes. The proteins are expressed in a tissue-restricted manner during development and in the adult. To elucidate the regulation of aldolase mRNA in the mouse liver, we analyzed its expression by a number of methods including Northern blot, RNA dot blot, and nuclear run-on assays. Our experiments demonstrate that the expression of aldolase A in the liver is primarily regulated by post-transcriptional control. In contrast, we found that changes in the level of aldolase B mRNA are due to changes in the rate of initiation of transcription. In addition, we examined the regulation of aldolase expression in the adult kidney. We found that although the kidney has eight times more aldolase B than the liver, the rate of initiation of transcription is similar in both tissues. Also, the rate of initiation of transcription of aldolase A is the same in the adult kidney and liver although there is 40 times more steady state aldolase A mRNA in the kidney than in the liver.
 ...
PMID:Distinct developmental regulatory mechanisms for two members of the aldolase gene family. 182 33

To assess changes in aldolase isozyme patterns (A, B, and C) in renal cell carcinoma (RCC) tissues and to evaluate whether serum aldolase A might be a useful marker for RCC, quantitative analysis by enzyme immunoassay and immunohistochemical localization were performed. Concentrations of aldolase A in RCC (7300 +/- 6300 ng./mg. protein n = 26) were significantly higher than those of normal cortex (720 +/- 410 ng./mg. protein, n = 14, p less than 0.01); concentrations of aldolase C in RCC (48.0 +/- 8.0 ng./mg. protein) were also significantly higher than those of normal cortex (8.7 +/- 4.7 ng./mg. protein, p less than 0.01). On the other hand, concentrations of aldolase B in normal cortex were 18,100 +/- 10,100 ng./mg. protein (n = 14), whereas the values in RCC were only 130 +/- 270 ng./mg. protein, a significant lowering (p less than 0.01). Immunohistochemically, aldolases A and C were found localized in all RCC tissues (n = 10); aldolase B was faintly stained in only a few tumor cells of two cases (20%). Levels of serum aldolase A were elevated (greater than 300 ng./ml.) in 30 (75%) of 40 patients with RCC as compared to three (6.3%) of 48 individuals with urogenital benign diseases and in seven (21%) of 34 cases with non-RCC urogenital malignancies. Since it is generally accepted that RCC are derived from renal proximal tubules, these findings indicate that aldolase B, the predominant isozyme in the normal case, changes into aldolases A and C during carcinogenesis and that serum aldolase A could be a new useful biomarker for RCC.
 ...
PMID:An immunochemical and immunohistochemical study of aldolase isozymes in renal cell carcinoma. 185 54

Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients exhibit a deficiency of fructose 1-phosphate aldolase (aldolase B), the isozyme expressed in tissues that metabolize fructose. The eight protein-coding exons, including splicing signals, of the aldolase B gene from one HFI patient were amplified by PCR. Dot-blot hybridization of the amplified DNA with allele-specific oligonucleotide (ASO) probes revealed a previously described A149P mutation in one allele from the proband. The mutation in the other allele was identified by direct sequencing of the double-stranded PCR-amplified material from the proband. The nucleotide sequence of exon 9 revealed a 7-base deletion/1-base insertion (delta 7 + 1) at the 3' splice site of intron 8 in one allele. This mutation was confirmed by cloning PCR-amplified exon 9 of the proband and determining the sequence of each allele separately. ASO analysis of 18 family members confirmed the Mendelian inheritance of both mutant alleles. The implications of this unique splice-site mutation in HFI are discussed.
 ...
PMID:Identification of a splice-site mutation in the aldolase B gene from an individual with hereditary fructose intolerance. 192 90

The aldolase isozymes A, B, and C in tumor tissues (63) and sera (104) of patients with lung cancer were determined with an enzyme immunoassay system, compared with normal lung tissues (13), and the sera of normal healthy subjects (100). Tissue aldolase A and C concentrations were enhanced in 83% (52/63) and 51% (32/63) of patients with lung cancer, respectively, regardless of histologic type or stage (P less than 0.01). But aldolase B was not elevated in tissue levels. In the sera of patients with lung cancer, there were no significant elevations of the isozymes. Immunohistochemically aldolase A and C stained more intensely in the cytoplasm of lung cancer cells than those in normal tissues. These results indicate lung cancer cells contain enhanced tissue levels of aldolase A and C.
 ...
PMID:Immunochemical and immunohistochemical studies on three aldolase isozymes in human lung cancer. 200 36

Enzymatic studies on aldolase isozymes have been carried out by techniques of protein engineering. Site-directed mutagenesis helps us to verify the roles of amino acid residues in catalytic reactions. Chimeric fusion proteins give us information about the regions which specify the characteristics of the isozymes. The results are: (1) In aldolase A, COOH terminal Tyr and Lys-107 residues play important roles in catalysis, especially in binding of FDP. (2) Aspartic acid at the 128th residue in aldolase A is essential to thermostability; no other residue such as glutamic acid can substitute for it. (3) Studies on chimeric fusion proteins indicate that the C-terminal region (including C-terminus Tyr) or aldolase A is responsible for its substrate specificity, which is not seen in aldolase B. (4) A region near NH2 terminus in aldolase B determines its specific structure. (5) The region including His-107, Asp-128, and Tyr-137 (B-A junction of BA137) is located in a turn which is exposed outward (a model architecture by Sygusch et al [1987]). In BA137, this region would be constrained, and play a significant role in catalysis, thermostability, etc. (6) Tertiary structure of aldolase B seems to be dissimilar to that of aldolase A.
 ...
PMID:Structural studies on aldolase isozymes through protein engineering. 220 67


1 2 3 4 5 6 7 8 9 10 Next >>