Arachidonic fatty acid in red blood cell membranes, lymphocytes, and cultured skin fibroblasts of dominant Charcot-Marie-Tooth syndrome.
Altered proportions of long-chain unsaturated n - 6 fatty acids (FA) in plasma and myelin of the heredodegenerative peripheral neuropathy, Charcot-Marie-Tooth syndrome (CMT), may implicate FA metabolism in the pathogenesis of CMT demyelination. A significant relationship between low plasma values of the polyunsaturated n - 6 FA, arachidonic acid, and an increased amount of prostaglandin-mediated immune responses had suggested the possibility of immune system metabolic usage of these n - 6 FA rather than an inherited FA enzyme defect. This relationship between peripheral immunostimulation and altered FA was documented repeatedly in CMT patients. Increased and cyclic lymphocyte activation expressions were measured at the same time as low amounts of plasma arachidonic acid, which is the FA precursor of prostaglandin immunoregulatory agents. An autoimmune process with possible enhanced formation of the n - 6 immune prostenoid agents in CMT had also been suggested by increased class II antigen expression on CMT sural nerves. Here, normal proportions of total FA in cultured CMT skin fibroblasts diminishes a notion of hereditary defects in CMT fatty acid metabolism. In addition, a significant depletion of the key arachidonic acid in lipid stores of CMT red blood cell membranes with elevated values of this FA in functional CMT lymphocytes, compared to controls, support the concept in CMT patients of a metabolic diversion of n - 6 FA, particularly arachidonic acid, from tissue stores for immunoregulatory prostenoid agent formation.
Williams
L L
LL
Department of Pediatric Neurology, Ohio State University College of Medicine, Columbus.
Wright
F S
FS
D000293:Adolescent; D000328:Adult; D001095:Arachidonic Acids / Q000097:blood*; D002607:Charcot-Marie-Tooth Disease / Q000097:blood / Q000378:metabolism*; D002648:Child; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000166:cytology
D001095:Arachidonic Acids; D005227:Fatty Acids