Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

International Journal of Molecular Sciences - Tập 17 Số 12 - Trang 2069
Saúl Gómez‐Manzo1, Jaime Marcial‐Quino2, América Vanoye–Carlo3, Hugo Serrano‐Posada4, Daniel Ortega‐Cuellar5, Abigail González‐Valdez6, Rosa Angélica Castillo‐Rodríguez2, Beatriz Hernández‐Ochoa7, Edgar Sierra-Palacios8, Eduardo Rodríguez-Bustamante9, Roberto Arreguín‐Espinosa9
1Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud 04530, Mexico
2Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Pediatría, Secretaría de Salud 04530, Mexico
3Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud 04530, Mexico
4Consejo Nacional de Ciencia y Tecnología (CONACYT), Laboratorio de Bioingeniería, Universidad de Colima, Colima 28400, Mexico
5Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud 04530, Mexico
6Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
7Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
8Colegio de Ciencias y Humanidades, Plantel Casa Libertad, Universidad Autónoma de la Ciudad de México, Mexico City 09620, Mexico
9Departamento de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Mexico City 04510, Mexico

Tóm tắt

Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the pentose phosphate pathway which produces nicotinamide adenine dinucleotide phosphate (NADPH) to maintain an adequate reducing environment in the cells and is especially important in red blood cells (RBC). Given its central role in the regulation of redox state, it is understandable that mutations in the gene encoding G6PD can cause deficiency of the protein activity leading to clinical manifestations such as neonatal jaundice and acute hemolytic anemia. Recently, an extensive review has been published about variants in the g6pd gene; recognizing 186 mutations. In this work, we review the state of the art in G6PD deficiency, describing 217 mutations in the g6pd gene; we also compile information about 31 new mutations, 16 that were not recognized and 15 more that have recently been reported. In order to get a better picture of the effects of new described mutations in g6pd gene, we locate the point mutations in the solved three-dimensional structure of the human G6PD protein. We found that class I mutations have the most deleterious effects on the structure and stability of the protein.

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