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

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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)

In 38 patients with chronic renal insufficiency of different degree of severity examinations of the stationary concentration of the adenine nucleotides in the erythrocytes were carried out. It was shown that in the red blood cells of uraemics a genuine increase of the concentration of these compounds occurs, in which case the adenosine triphosphate dominates absolutely as well as relatively. In individual cases erytho-cyctic ATP-values of more than 3 micron mol pro ml cells may be achieved. The increase of the ATP-concentration in the red blood cells correlates with the degree of severity of the renal insufficiency and the renal anaemia. The hyperphosphataemia occurring as a rule in renal insuficiency is of causal importance for the increase of ATP. By a consecutive increase of the intracellular phosphate level and by influence on different steps of enzymes (phosphofructokinase, aldolase, glycerin aldehyde phosphate dehydrogenase) and changed regulations it effected an activation of the glycolysis. The increase of the plasma adenine and plasma adenosine concentration plays apparantly an accessory role for the increase of the concentration of the adenine nucleotides existing in the erythrocytes. Together with an increased concentration of 2,3-diphosphogycerate (2,3-DPG) the increase of the ATP-level has an effect on the oxygen transport function function of haemoglobin in the sense of a facilitation of the O2-output. These processes explain the relative adaption of patients with chronic renal insufficiency to renal anaemias of partly high degree.
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PMID:[Adenine nucleotide- and 2,3-diphosphoglycerate metabolism in human erythrocytes in chronic kidney insufficiency]. 84 44

It is generally recognized that the activities of some of the red cell enzymes decline as the cell ages. However, there is still a controversy regarding the rate at which this aging occurs. In the present study we applied newly developed technology for the specific isolation of maturing reticulocytes/erythrocytes for a more comprehensive study of in vivo aging of red cell enzymes in rabbits. Anemia was induced by repeated phlebotomy, and reticulocyte-rich erythrocytes were labeled with N-hydroxy succinimido-biotin and then transfused into a normal rabbit. These biotinylated cells were isolated at various time points by their affinity for an avidin support, and the enzymatic activity of 19 red cell enzymes was measured. We observed a biphasic pattern of decay for the activity of six age-dependent enzymes--aldolase, glutamate-oxaloacetate transaminase, glucose 6-phosphate dehydrogenase, hexokinase, pyrimidine 5'-nucleotidase, and pyruvate kinase.
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PMID:In vivo aging of red cell enzymes: study of biotinylated red blood cells in rabbits. 231 8

A patient with Graves' disease associated with severe muscle weakness who was finally diagnosed as polymyositis by pathological examination of the muscle is reported. A 28-year-old women was incidentally found to have hyperthyroidism when she consulted a hospital for the evaluation and treatment of anemia in 1979. She was treated with methimazole for approximately a month when she stopped the medication by herself. Approximately two yr later (Nov. 4, 1981) she consulted another hospital with complaints of palpitation and muscle weakness. Diagnosis of hyperthyroidism due to Graves' disease and thyrotoxic myopathy were made, followed by the treatment with radioiodine (4 mCi of 131I). She was further treated with propylthiouracil (PTU). Four yr after the treatment, serum thyroid hormone concentration declined to the lower level than normal and serum TSH concentration increased. She was subsequently treated with synthetic I-T4. Despite the fact she became euthyroid with the treatment, muscle weakness as well as elevated concentrations of muscle enzymes were not improved. Muscle biopsy was made in July 1983, and she was diagnosed as immune polymyositis and treatment with prednisolone and cyclophosphamide in addition to PTU or I-T4, was started. With the treatment, serum LDH decreased to the normal range. However she still has muscle weakness and serum concentrations of CPK and aldolase are still in higher levels than normal range.
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PMID:A case of Graves' disease associated with polymyositis. 209 Jun 76

The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW = 330 +/- 32 g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments.
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PMID:Short-term toxicity study of 4-dimethylaminoazobenzene in marmosets. 310 51

Two cases of red cell aldolase deficiency associated with congenital nonspherocytic hemolytic anemia are reported. The proband is a fourteen-month-old Japanese boy. Consanguineous marriage was not proven but probable in this family, as the parents were born in the same small island. The proband had moderate to mild anemia aggravated by upper respiratory infections, 1 cm hepatomegaly and 2.5 cm splenomegaly, but was unremarkable in other respects and has thus far not shown mental or growth retardation. He did not have dysmorphic features. The red cell aldolase activity was 6% of the normal mean. The enzyme was unstable with respect to heat, and Km for fructose 1,6-diphosphate (F-1,6-DP) was high. The parents and other heterozygotes showed intermediate activity between that of the proband and that of normal subjects. Red cell F-1,6-DP concentration in this case was remarkably increased. Red cell glucose consumption, and lactate formation, as well as hexose monophosphate shunt activity, were decreased as compared with a comparable reticulocyte-rich hereditary spherocytosis patient. Hexose monophosphate dehydrogenase by a high concentration of F-1,6-DP in his red cells. As a result of family study, another homozygous aldolase deficiency case associated with hemolytic anemia was found. He is 13 years old and a nephew of the proband's paternal grandmother. His hemolytic anemia also is moderate to mild and aggravated by upper respiratory infections. He does not seem to have mental or growth retardation, nor does he possess dysmorphic features.
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PMID:Two cases of red cell aldolase deficiency associated with hereditary hemolytic anemia in a Japanese family. 733 96

In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxoprolinuria, but without neurological manifestations. The family study revealed GSH-S activity in both parents to be around half the normal level, a finding consistent with the presumed autosomal recessive mode of inheritance of this enzymopathy. Two cases exhibited a well-compensated haemolytic syndrome without anaemia or splenomegaly at steady state. One of these cases was diagnosed after an episode of acute haemolytic anaemia after fava bean ingestion. The remaining patient suffered from moderate to severe chronic non-spherocytic haemolytic anaemia and splenomegaly, and required occasional blood transfusion for a haemolytic crisis associated with drug ingestion. In this patient, the anaemia was corrected by splenectomy. In addition to GSH-S, a panel of 16 other RBC enzyme activities was also studied in all the patients. Hexokinase, aldolase, glucose-6-phosphate dehydrogenase and pyruvate kinase activities all increased; these increases were to be expected, given the rise in the number of circulating reticulocytes. In two patients, the incubation of RBCs with hydrogen peroxide revealed an enhanced production of malonyldialdehyde. DNA analysis showed a homozygous state for 656 A-->G mutation in patients 2 and 3. The GSH-S gene of patient 1, studied elsewhere, revealed an 808 T-->C. The GSH-S gene of patient 4 was not available for study. The present study demonstrates that GSH-S deficiency is also present in Spain and further supports the molecular and clinical heterogeneity of this enzymopathy
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PMID:Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies. 1116 50

Aldolase (E.C. 4.1.2.13), a homotetrameric protein encoded by the ALDOA gene, converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Three isozymes are encoded by distinct genes. The sole aldolase present in red blood cells and skeletal muscle is the A isozyme. We report here the case of a girl of Sicilian descent with aldolase A deficiency. Clinical manifestations included transfusion-dependent anemia until splenectomy at age 3 and increasing muscle weakness, with death at age 4 associated with rhabdomyolysis and hyperkalemia. Sequence analysis of the ALDOA coding regions revealed 2 novel heterozygous ALDOA mutations in conserved regions of the protein. The paternal allele encoded a nonsense mutation, Arg303X, in the enzyme-active site. The maternal allele encoded a missense mutation, Cys338Tyr, predicted to cause enzyme instability. This is the most severely affected patient reported to date and only the second with both rhabdomyolysis and hemolysis.
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PMID:Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr). 1563 14

The 911 amino acid band 3 (SLC4A1) is the major intrinsic membrane protein of red cells and is the principal Cl-/HCO3- exchanger. The N-terminal cytoplasmic domain of band 3 anchors the spectrin-based membrane skeleton to the lipid bilayer through its interaction with ankyrin and also binds glycolytic enzymes and hemoglobin. We identified a son of a consanguineous marriage with severe anemia in association with marked deficiency of band 3 (12% +/- 4% of normal). Direct nucleotide sequencing of SLC4A1 gene demonstrated a single base substitution (T --> C) at position + 2 in the donor splice site of intron 2, resulting in the generation of a novel mutant protein. Biochemical characterization of the mutant protein showed that it lacked the first 11 N-terminal amino acids (band 3 Neapolis). The expression of the mutant protein resulted in the complete absence of membrane-bound aldolase, and the mutant band 3 could not be tyrosine phosphorylated. The ability of the malarial parasite P falciparum to invade these red cells was significantly decreased. The identification of a novel band 3 mutant and its structural and functional characterization enabled us to identify pivotal roles for the 11 N-terminal amino acids in several protein functions and, in turn, in red-cell physiology.
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PMID:The N-terminal 11 amino acids of human erythrocyte band 3 are critical for aldolase binding and protein phosphorylation: implications for band 3 function. 1611 13

Little is known about the vascular and metabolic adaptations that take place in the fetal heart to maintain cardiac function in response to increased load. Chronic fetal anemia has previously been shown to result in increased ventricular mass, increased myocardial vascularization, and increased myocardial expression of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF). We therefore sought to determine whether chronic fetal anemia induces expression of HIF-1-regulated angiogenic factors and glycolytic enzymes in the fetal myocardium. Anemia was produced in chronically instrumented fetal sheep by daily isovolemic hemorrhage (80-100 ml) for either 3 (n = 4) or 7 days (n = 11) beginning at 134 days of gestation (term 145 days). Catheterized, nonbled twins served as controls. Isovolemic hemorrhage over 7 days resulted in decreased fetal hematocrit (37 +/- 1 to 20 +/- 1%) and arterial oxygen content (6.5 +/- 0.4 to 2.8 +/- 0.2 ml O2/dl). Myocardial blood flow and vascularization were significantly increased after 7 days of anemia. Myocardial HIF-1 protein expression and VEGF (left ventricular), VEGF receptor-1 (right ventricular), and VEGF receptor-2 (right ventricular, left ventricular) mRNA levels were elevated (P < 0.05) in 7-day anemic compared with control animals. Myocardial expressions of the glycolytic enzymes aldolase, lactate dehydrogenase A, phosphofructokinase (liver), and phosphoglycerol kinase were also significantly elevated after 7 days of anemia. Despite the absence of a significant increase in myocardial HIF-1alpha protein in 3-day anemic fetuses, expressions of VEGF, VEGF receptor-1, and the glycolytic enzymes were greater in 3-day compared with 7-day anemic animals. These data suggest that HIF-1 likely participates in the fetal myocardial response to anemia by coordinating an increase in gene expressions that promote capillary growth and anaerobic metabolism. However, factors other than HIF-1 also appear important in the regulation of these genes. We speculate that the return of mRNA levels of angiogenic and glycolytic enzymes toward control levels in the 7-day anemic fetus is explained by a significantly increased resting myocardial blood flow, resulting from coronary vascular growth and increased coronary conductance, and a return to a state of adequate oxygen and nutrient delivery, obviating the need for enhanced transcription of genes encoding angiogenic and glycolytic enzymes.
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PMID:Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep. 1612 31

A 57-year-old man underwent an autologous hematopoietic stem cell transplant for mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in November 2001. He was diagnosed with further hematological examination as having acute myeloid leukemia with multilineage dysplasia following secondary myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell transplant from his HLA DRB1 locus mismatched brother in May 2002. The nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD gradually improved. He had fever and myalgia in the extremities and lumbar region with elevated serum CPK and aldolase in January 2003. Histological examination led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone 50 mg/day as an initial dose was started for the polymyositis following which the prednisolone dose was gradually tapered off. The polymyositis improved promptly after the administration of prednisolone and remains in remission with a current maintenance program of prednisolone 5 mg/day.
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PMID:[Chronic GVHD with polymyositis after non-myeloablative stem cell transplantation]. 1644 Aug 6


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