Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish
We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no. 1436 from the translational initiation site of t...
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| Veröffentlicht in: | Blood 1994-04, Vol.83 (8), p.2311-2316 |
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| creator | KANNO, H BALLAS, S. K MIWA, S FUJII, H BOWMAN, H. S |
| description | We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no. 1436 from the translational initiation site of the R-type PK (R-PK) mRNA, and it caused a single amino acid substitution from Arg to His at the 479th amino acid residue of the R-PK. The substituted Arg residue is located in the C domain of PK subunit, that is essential for both the intersubunit contact and the allosteric regulation. Because this enzyme shows the catalytic activity only as a dimer or tetramer, it is rational that the structural alteration would result in severe PK deficiency. To elucidate the effect of the PK deficiency on red blood cell (RBC) membrane, we performed the cellular studies of the patients' RBCs. Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs. |
| doi_str_mv | 10.1182/blood.v83.8.2311.2311 |
| format | Article |
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To elucidate the effect of the PK deficiency on red blood cell (RBC) membrane, we performed the cellular studies of the patients' RBCs. Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.v83.8.2311.2311</identifier><identifier>PMID: 8161798</identifier><language>eng</language><publisher>Washington, DC: The Americain Society of Hematology</publisher><subject>Adult ; Amino Acid Sequence ; Anemias. 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K</creatorcontrib><creatorcontrib>MIWA, S</creatorcontrib><creatorcontrib>FUJII, H</creatorcontrib><creatorcontrib>BOWMAN, H. S</creatorcontrib><title>Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish</title><title>Blood</title><addtitle>Blood</addtitle><description>We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no. 1436 from the translational initiation site of the R-type PK (R-PK) mRNA, and it caused a single amino acid substitution from Arg to His at the 479th amino acid residue of the R-PK. The substituted Arg residue is located in the C domain of PK subunit, that is essential for both the intersubunit contact and the allosteric regulation. Because this enzyme shows the catalytic activity only as a dimer or tetramer, it is rational that the structural alteration would result in severe PK deficiency. To elucidate the effect of the PK deficiency on red blood cell (RBC) membrane, we performed the cellular studies of the patients' RBCs. Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs.</description><subject>Adult</subject><subject>Amino Acid Sequence</subject><subject>Anemias. Hemoglobinopathies</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Diseases of red blood cells</subject><subject>Erythrocytes - enzymology</subject><subject>Ethnic Groups</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Pedigree</subject><subject>Point Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>Potassium - metabolism</subject><subject>Pyruvate Kinase - deficiency</subject><subject>Pyruvate Kinase - genetics</subject><subject>Structure-Activity Relationship</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UMtOwzAQtBColMInVMoBcUvxK8nmWFW8pCIuwNVynLUaSOJiJ5Xy96QP9TK72pnZkYaQOaMLxoA_FrVz5WIHYgELLhg7wAWZsoRDTCmnl2RKKU1jmWfsmtyE8EMpk4InEzIBlrIshylZv7saTV9rH-midb7RddUNkbMR-qHbeGeGDqPt4PudHpffqtUBoxJtZSpszRBVbdRtMFo2Vdjckiur64B3pzkjX89Pn6vXeP3x8rZarmMjMujiRMqyyK3JJJgihRLKtNASilIbBingeBGAWYLAjeXWcpFgqrnJSprLVCZiRh6Of7fe_fUYOjWmG6xr3aLrg8r2IpmJUZgchca7EDxatfVVo_2gGFX7FtWhRfUNQoHaF3iA0Tc_BfRFg-XZdapt5O9PvA5G19br1lThLJM0ZZJz8Q-EvX1P</recordid><startdate>19940415</startdate><enddate>19940415</enddate><creator>KANNO, H</creator><creator>BALLAS, S. 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Hemoglobinopathies</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Diseases of red blood cells</topic><topic>Erythrocytes - enzymology</topic><topic>Ethnic Groups</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Pedigree</topic><topic>Point Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Potassium - metabolism</topic><topic>Pyruvate Kinase - deficiency</topic><topic>Pyruvate Kinase - genetics</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KANNO, H</creatorcontrib><creatorcontrib>BALLAS, S. K</creatorcontrib><creatorcontrib>MIWA, S</creatorcontrib><creatorcontrib>FUJII, H</creatorcontrib><creatorcontrib>BOWMAN, H. 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S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1994-04-15</date><risdate>1994</risdate><volume>83</volume><issue>8</issue><spage>2311</spage><epage>2316</epage><pages>2311-2316</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no. 1436 from the translational initiation site of the R-type PK (R-PK) mRNA, and it caused a single amino acid substitution from Arg to His at the 479th amino acid residue of the R-PK. The substituted Arg residue is located in the C domain of PK subunit, that is essential for both the intersubunit contact and the allosteric regulation. Because this enzyme shows the catalytic activity only as a dimer or tetramer, it is rational that the structural alteration would result in severe PK deficiency. To elucidate the effect of the PK deficiency on red blood cell (RBC) membrane, we performed the cellular studies of the patients' RBCs. Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs.</abstract><cop>Washington, DC</cop><pub>The Americain Society of Hematology</pub><pmid>8161798</pmid><doi>10.1182/blood.v83.8.2311.2311</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Blood, 1994-04, Vol.83 (8), p.2311-2316 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Amino Acid Sequence Anemias. Hemoglobinopathies Base Sequence Biological and medical sciences Diseases of red blood cells Erythrocytes - enzymology Ethnic Groups Female Hematologic and hematopoietic diseases Humans Male Medical sciences Molecular Sequence Data Pedigree Point Mutation Polymerase Chain Reaction Potassium - metabolism Pyruvate Kinase - deficiency Pyruvate Kinase - genetics Structure-Activity Relationship |
| title | Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish |
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