Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human erythrocyte generates high-energy adenosine triphosphate by anaerobic glycolysis and cycles oxidized and reduced nicotinamide adenine dinucleotide phosphate by the aerobic pentose phosphate shunt pathway. Certain enzymopathies of the pentose phosphate shunt are associated with hemolysis resulting from oxidative denaturation of hemoglobin. Glucose-6-phosphate dehydrogenase deficiency, an X-chromosome-linked disorder, is the prototype of these diseases and is genetically and clinically polymorphic. Six enzymopathies of anaerobic glycolysis cause hemolytic anemia; lactate dehydrogenase deficiency does not. In 2,3-diphosphoglycerate mutase deficiency, 2,3-diphosphoglycerate is greatly reduced and asymptomatic polycythemia is noted. Pyrimidine-5'-nucleotidase deficiency, an enzymopathy of nucleotide metabolism, is characterized by intracellular accumulations of pyrimidine-containing nucleotides, marked basophilic stippling on the stained blood film, splenomegaly, and hemolysis. Lead inhibits the nucleotidase and an identical syndrome occurs during severe lead poisoning. Hemolysis also accompanies an unusual enzymopathy characterized by a 40- to 70-fold increase (not decrease) in adenosine deaminase activity.
 ...
PMID:Hemolytic anemias and erythrocyte enzymopathies. 299 Feb 76

Erythrocyte 2,3-diphosphoglycerate levels are determined principally by a single molecule which has both diphosphoglycerate mutase (DPGM) and diphosphoglycerate phosphatase activities. An antiserum containing precipitating antibodies against this molecule was used to measure its amount in red cells from normal controls, from subjects with hypothyroidism or hyperthyroidism, and from a Japanese proband who has hemolytic anemia attributed to heterozygosity for a genetic variant. The amount of DPGM in normal adult erythrocytes is 0.98 +/- 0.014 mg/gm Hb. Slightly increased amounts are found in normal cord blood and in subjects with hyperthyroidism. Hypothyroid subjects have a significantly decreased concentration of DPGM, 0.82 +/- 0.06 mg/gm Hb. Restoration of euthyroid status during treatment results in a return of DPGM amounts to normal. The red cells of the Japanese subject contained 0.67 mg/gm Hb of DPGM as measured by immunoprecipitation.
 ...
PMID:Physiologic and genetic alterations in human red cell DPGM. 625 18

Phosphoglycerate kinase deficiency is a rate, X-linked disorder associated with a severe haemolytic anaemia. In general the deficiency has been demonstrated only in erythrocytes and leucocytes. However, in a subject with this condition, the activity of phosphoglycerate kinase in lymphocytes and platelets was also shown to be less than 5% of the normal value. Following the death of this subject in 1979, the deficiency was also found to occur in tissue samples of brain, skeletal muscle, liver and cardiac muscle, obtained at the autopsy. Values for phosphoglycerate kinase were of the order of 0.5-5% of normal controls. Other glycolytic enzymes which were tested were hexokinase, pyruvate kinase, enolase and 2-phosphoglyceromutase. In general, values for these enzymes were either normal or slightly raised.
 ...
PMID:Tissue levels of glycolytic enzymes in phosphoglycerate kinase deficiency. 625 1

Molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined by means of molecular biology. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency in the glycolytic pathway, and it causes hereditary hemolytic anemia. To date, 47 gene mutations have been identified. We identified one base deletion, one splicing mutation, and six distinct missense mutations in 12 unrelated families with a homozygous PK deficiency. Mutations located near the substrate or fructose-1,6- diphosphate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Glucose-6-phosphate dehydrogenase (G6PD)deficiency is the most common metabolic disorder, and it is associated with chronic hemolytic anemia and/or drug- or infection-induced acute hemolytic attack. An estimated 400 million people are affected worldwide. The mutations responsible for about 78 variants have been determined. Some have polymorphic frequencies in different populations. Most variants are produced by one or two nucleotide substitutions. Molecular studies have disclosed that most of the class 1 G6PD variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in deficiencies of glucosephosphate isomerase, (TPI), phosphoglycerate kinase, and adenylate kinase. Compound heterozygosity with missense mutation and base deletion has been determined in deficiencies of hexokinase and diphosphoglyceromutase. Compound heterozygosity with missense and nonsense mutations has been identified in TPI deficiency. One base junction mutations resulting in abnormally spliced PFK-M mRNA have been identified in homozygous PFK deficiency. An exception is hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from the overproduction of a structurally normal enzyme.
 ...
PMID:Molecular basis of erythroenzymopathies associated with hereditary hemolytic anemia: tabulation of mutant enzymes. 857 52

The molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined using molecular techniques. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency involving the glycolytic pathway and causing hereditary hemolytic anemia. We have identified six distinct missense mutations and a form of splicing mutation in 11 unrelated families with homozygous PK deficiency. Mutations located near the substrate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Up to now, including these genetic defects, 21 missense, 1 nonsense and 2 splicing mutations, 2 insertions, and 3 deletions have been determined. G6PD deficiency is the most common metabolic disorder, and is associated with chronic and drug- or infection-induced hemolytic anemia. To date, sixty different mutations have now been identified. Except for three kinds of variants with small gene deletions or three nucleotide substitutions, all of those were found to be produced by one or two nucleotide substitutions. Molecular studies disclosed that all the class 1 variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in glucosephosphate isomerase deficiency, aldolase deficiency, triosephosphate isomerase (TPI) deficiency, phosphoglycerate kinase deficiency, and adenylate kinase deficiency. Compound heterozygous cases with missense mutation/nonsense mutation and missense mutation/decreased mRNA have been reported in TPI deficiency and diphosphoglyceromutase deficiency, respectively. In phosphofructokinase (PFK) deficiency, three kinds of 5'-splice junction mutations resulting in abnormally spliced PFK-M mRNA were identified. An exception is a hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from overproduction of structurally normal enzyme.
 ...
PMID:Red cell enzymopathies as a model of inborn errors of metabolism. 862 88