RESUMEN
The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer's disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct Ca(2+) dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.
Asunto(s)
Cognición/fisiología , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación Missense/genética , Fosfatidilinositoles/metabolismo , Fosfoproteínas/genética , Exones/genética , Exones/fisiología , Femenino , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular/fisiología , Desequilibrio de Ligamiento/genética , Desequilibrio de Ligamiento/fisiología , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Masculino , Persona de Mediana Edad , Mutación Missense/fisiología , Pruebas Neuropsicológicas , Fosfoproteínas/fisiología , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Free amino acids and urea were analyzed in 78 human milk samples obtained during the first 5 wk of lactation from 10 mothers delivering at term. Significant differences (p less than 0.05) in the concentrations between colostral and mature milk were found for glutamic acid, glutamine, alanine, glycine, cystine, and phosphoethanolamine which increased, and with serine, phosphoserine, aspartic acid + asparagine, arginine, lysine, isoleucine, phenylalanine, proline, methionine, tryptophan, and beta-alanine which decreased. Some of these changes occurred within the first 5 days of lactation, so that differences between transitional and mature milk became negligible (glutamic acid, alanine, and serine, aspartic acid + asparagine, lysine, isoleucine, methionine, tryptophan, respectively). No significant differences between any of the three stages of lactation were found regarding the concentrations of total free amino acids, urea, taurine, threonine, valine, leucine, histidine, and tyrosine. Possible relevances for free amino acids, including nonprotein ones, in human milk are discussed.
