The amino acid substitution and some chemical properties of a variant human erythrocyte carbonic anhydrase: Carbonic anhydrase IdMichigan

Shows, Thomas B.

doi:10.1007/bf00486517

Cited by 39 publications

(7 citation statements)

References 35 publications

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“…This enzyme, representing about 5 o/, of the total red cell carbonic anhydrase, was indistinguishable from human carbonic anhydrase B in terms of its specific activity, amino acid composition and tryptic peptides [43]. In addition, mutants of the B isozyme were accompanied by a corresponding change in A [44]. Consequently, it was concluded that this form of the enzyme resulted from an epigenetic modification of carbonic anhydrase B, possibly as a results of amide group hydrolysis [17].…”

Section: Discussionmentioning

confidence: 99%

Purification, Molecular Properties and Ontogeny of Carbonic Anhydrase Isozymes. Evidence for A, B and C Isozymes in Avian and Mammalian Tissues

Holmes

1977

Eur J Biochem

105

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Carbonic anhydrase A from sheep and chicken red skeletal muscles and carbonic anhydrases B and C from chicken intestine and red cells respectively have been isolated in a high state of purity by affinity chromatography. The subunit and native molecular weights of sheep carbonic anhydrase A determined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and Sephadex gel filtration respectively were both approximately 34000. In contrast, carbonic anhydrases A, B and C from chicken exhibited a molecular weight determined by sodium dodecyl sulphate electrophoresis of 30000. The amino acid composition of sheep muscle carbonic anhydrase A was distinct from the B and C isozymes, particularly in basic amino acid content, which was significantly higher for the A isozyme (38 cJ: 24-291mol). The zinc content of sheep carbonic anhydrase A was found to be 0.81 g atom Zn/mol. The specific activities of chicken carbonic anhydrase isozyme differed significantly according to the ratio A:B:C = 1 :6:47. In addition, these isozymes differed in their affinities for sulphonamide. Chicken carbonic anhydrase A was approximately 100 times less sensitive to acetazolamide inhibition than the chicken C isozyme. Ontogenetic studies in cats showed carbonic anhydrase C to be the only form of the enzyme present in mid-term fetal animals, with carbonic anhydrase A appearing in muscle in the late stages, and carbonic anhydrase B appearing in caecum within 2 days of birth.The evidence is consistent with previous proposals for a third locus encoding carbonic anhydrase in mammalian and avian species. This isozyme (A) is a monomeric, zinc metalloenzyme, which differs from the extensively studied B and C isozymes of carbonic anhydrase in terms of catalytic efficiency, amino acid composition, molecular weight (in sheep), time of ontogenic appearance, sulphonamide inhibition and tissue distribution.

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Section: Discussionmentioning

confidence: 99%

Purification, Molecular Properties and Ontogeny of Carbonic Anhydrase Isozymes. Evidence for A, B and C Isozymes in Avian and Mammalian Tissues

Holmes

1977

Eur J Biochem

105

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“…It is also improbable that a genetically determined abnormality of the blood would be highly polymorphic in several discrete feral mouse populations. When techniques were used for their specific detection, electrophoretic analysis of hemoglobin, protein, and ten erythrocytic enzymes showed no obvious differences between B+ and B -airnals.9, 6-18, [32][33][34][35][36] Further support for a LDH controlling gene in mouse erythrocytes comes from phylogenetic data obtained from red cell LDH phenotypes of 26 different rodent species from the three rodent suborders (myomorpha, Sciuromorpha, Hystricomorpha).37 The red cell LDH zymograms of myomorphs show a predominance of A subunits and therefore LDH-5. Both A and B LDH subunits are expressed in sciuromorphs, resulting in all 5 LDH isozymes.…”

Section: *4mentioning

confidence: 99%

Function of the lactate dehydrogenase B gene in mouse erythrocytes: evidence for control by a regulatory gene.

Shows¹,

Ruddle²

1968

Proc. Natl. Acad. Sci. U.S.A.

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Experimental evidence suggests that cells comprising complex multicellular organisms possess qualitatively equivalent ensembles of genes, but the differentiation of these cells requires differential gene expression. According to this hypothesis, differentiation occurs primarily as the result of a patterned activation of certain genes and a repression of others. Developmental control of gene expression can operate at many levels, such as transcription, translation, end product alteration, or combinations of these. It is reasonable to expect that the control processes should themselves be genetically controlled and, as a result, that mutations affecting control should also occur. Evidence for mutations affecting certain levels of control in higher organisms exists in fungi, Drosophila, plants, and mammals.1-3 These examples provide some insight into the mechanisms controlling differential gene expression.In this report we present genetic evidence for a mammalian gene that appears to control the expression of an independent structural gene in a differentiated cell. This gene controls the appearance of the active B subunit, but not the A subunit, of the lactate dehydrogenase (LDH) tetramer in mouse erythrocytes. It has no detectable effect in any other tissue examined. Preliminary evidence has been reported elsewhere.4Lactate dehydrogenase (EC 1.1.1.27) is composed of two electrophoretically distinct subunits, A and B, which associate at random to form five tetrameric isozymes, each with a molecular weight of about 135,000.5 6 The five isozymes are generated by assortment of the A and B subunits into all possible combinations of four.7 Formulas for the five isozymes may be written as follows: BBBB = LDH-1; BBBA = LDH-2; BBAA = LDH-3; BAAA = LDH-4; AAAA = LDH-5. These five forms are the principal lactate dehydrogenase isozymes found ubiquitously in mammals. A high degree of tissue specificity characterizes isozyme patterns. Certain tissues contain more LDH-5 than LDH-1, thus demonstrating that unequal amounts of the A and B subunits are available for tetrameric association. Differential expression of the LDH isozymes has also been shown during specific tissue development.8 The developmental specificity of such tissue indicates that control mechanisms exist for regulating the relative amounts of synthesis of the A and B subunits of LDH.In the present study two lactate dehydrogenase phenotypes were observed in mouse erythrocytes but not in other tissues. In one phenotype, LDH B subunits were expressed, while in the second, LDH B subunits were absent. This phenotypic difference was inherited according to expectations of two alleles at an autosomal locus. The allele that specifies the formation of LDH B subunits is dominant to that which is associated with the absence of these subunits. 574

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“…It is of interest that despite the close proximity of these substitutions, and the fact that a lysyl residue has been substituted in both cases, the quantitative effects appear to be different. That is, the amount of CA Id in the variant hemolysate seems to be lower than the normal CA I (Shows, 1967), whereas in the CA If hemolysate the levels of the normal and variant enzymes appear to be present in approximately equal amounts.…”

Section: Discussionmentioning

confidence: 92%

“…Tryptic digestion was carried out as previously described for the CA Ie Hull and CA Ie Portsmouth variants (Carter et al, 1972), and chymotryptic digestion by the method of Shows (1967). One-dimensional electrophoretic separation of the peptides was carried out in a pyridine-acetate buffer (pH 6.5) for 3 hr at 3000 v. Guide strips were cut out, and the peptides were eluted with either 6 N HC1 or 1 N acetic acid.…”

Section: Peptide Analysismentioning

confidence: 99%

Characterization of a new variant of human red cell carbonic anhydrase I, CA if London (Glu-102?Lys)

et al. 1973

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A new inherited variant of red cell carbonic anhydrase I(CA I), designated CA If London, was discovered during a survey of 1615 individuals from London, England. No electrophoretic variants of the other isozyme of carbonic anhydrase CA II, were observed in the same survey. Sequence analysis of a lysine-blocked tryptie peptide believed to contain the amino acid substitution in CA If showed that the glutamyl residue at position 102 had been substituted by a lysyl residue. This substitution results in a net increase of two positive charges in the mutant enzyme. Densitometric scanning of the electrophoretically separated forms in the variant hemolysate indicates that the levels of the normal and variant enzymes are approximately equal.

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The amino acid substitution and some chemical properties of a variant human erythrocyte carbonic anhydrase: Carbonic anhydrase IdMichigan

Cited by 39 publications

References 35 publications

Purification, Molecular Properties and Ontogeny of Carbonic Anhydrase Isozymes. Evidence for A, B and C Isozymes in Avian and Mammalian Tissues

Purification, Molecular Properties and Ontogeny of Carbonic Anhydrase Isozymes. Evidence for A, B and C Isozymes in Avian and Mammalian Tissues

Function of the lactate dehydrogenase B gene in mouse erythrocytes: evidence for control by a regulatory gene.

Characterization of a new variant of human red cell carbonic anhydrase I, CA if London (Glu-102?Lys)

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