Possible role for protein kinase C in the pathogenesis of inborn errors of metabolism.
Protein kinase C (PKC) is a ubiquitous enzyme family implicated in the regulation of a large number of short- and long-term intracellular processes. It is hypothesized that modulation of PKC activity may represent, at least in part, a functional link between mutations (genotype) that lead to the pathological accumulation of naturally occurring compounds that affect PKC activity and perturbation of PKC-mediated substrate phosphorylation and cellular function in the corresponding diseases (phenotype). This model provides a unifying putative mechanism by which the phenotypic expression of some inborn errors of metabolism may be explained. Recent studies in a cell-free system of human skin fibroblasts support the hypothesis that alteration of PKC activity may represent the functional link between accumulation of sphingolipids and fatty acyl-CoA esters, and perturbation of cell function in sphingolipidoses and fatty acid oxidation defects, respectively. Further studies will elucidate the effects of these alterations on PKC-mediated short- and long-term cellular functions in these diseases, as well as the possible role of PKC in the pathogenesis of other diseases.
Department of Paediatrics, Hadassah University Hospital, Mt. Scopus, Jerusalem, Israel.
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Boneh
D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism
D005227:Fatty Acids; D013107:Sphingolipids; D011493:Protein Kinase C