菅野　仁    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Molecular basis of impaired pyruvate kinase isozyme conversion in erythroid cells: a single amino acid substitution near the active site and decreased mRNA content of the R-type PK.
Journal	Formal name：Biochemical and biophysical research communications Abbreviation：Biochem Biophys Res Commun ISSN code：0006-291X(Print)0006-291X(Linking)
Volume, Issue, Page	192(1),pp.46-52
Author and coauthor	Kanno H, Fujii H, Tsujino G, Miwa S
Publication date	1993/04
Summary	Conversion of pyruvate kinase (PK) isozymes from M2- to R-PK has been observed during erythroid cell maturation. To understand this mechanism, we analyzed the PK gene of a R-PK deficient patient, in whose erythrocytes the M2-PK was persistently expressed. A point mutation, 1102 GTC-->TTC was identified in the R-PK cDNA, and it caused a single amino acid substitution from 368Val-->Phe. The residue is very close to the 372nd Gln, the putative binding site of the monovalent cation (K+). The impaired K+ binding would cause the decreased affinity for phosphoenolpyruvate, consequently the variant PK may be extremely unstable. Although the proband's other PK allele did not have any structural change, the R-PK mRNA level in reticulocytes was decreased. These findings suggested that both the structural mutation near the active site and the decreased mRNA level of the R-PK were responsible for the disorder.
DOI	10.1006/bbrc.1993.1379
Document No.	8476433