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Cardiovascular & Hematological Disorders-Drug Targets
(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)
ISSN (Print): 1871-529X
ISSN (Online): 2212-4063
VOLUME: 9
ISSUE: 2
DOI: 10.2174/187152909788488636      Price:  $58









Red Cell Glycolytic Enzyme Disorders Caused by Mutations: An Update

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Author(s): Fernando Climent, Feliu Roset, Ada Repiso and Pablo Perez de la Ossa
Pages 95-106 (12)
Abstract:
Glycolysis is one of the principle pathways of ATP generation in cells and is present in all cell tissues; in erythrocytes, glycolysis is the only pathway for ATP synthesis since mature red cells lack the internal structures necessary to produce the energy vital for life. Red cell deficiencies have been detected in all erythrocyte glycolytic pathways, although their frequencies differ owing to diverse causes, such as the affected enzyme and severity of clinical manifestations. The number of enzyme deficiencies known is endless. The most frequent glycolysis abnormality is pyruvate kinase deficiency, since around 500 cases are known, the first of which was reported in 1961. However, only approximately 200 cases were due to mutations. In contrast, only one case of phosphoglycerate mutase BB type mutation, described in 2003, has been detected. Most mutations are located in the coding sequences of genes, while others, missense, deletions, insertions, splice defects, premature stop codons and promoter mutations, are also frequent. Understanding of the crystal structure of enzymes permits molecular modelling studies which, in turn, reveal how mutations can affect enzyme structure and function.
Keywords:
Glycolytic enzymes, mutations, red cells, structure
Affiliation:
Departament de Ciencies Fisiologiques I, Unitat de Bioquimica, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036 Barcelona, Spain.