title: Abnormal unsaturated fatty acid metabolism in cystic fibrosis: biochemical mechanisms and clinical implications.
abstract: Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of these changes, namely increased expression and activity of fatty acid desaturases. Among other effects, this drives metabolism of linoeate to arachidonate. Increased desaturase expression appears to be linked to cystic fibrosis mutations via stimulation of the AMP-activated protein kinase in the absence of functional CFTR protein. There is evidence that these abnormalities may contribute to disease pathophysiology by increasing production of eicosanoids, such as prostaglandins and leukotrienes, of which arachidonate is a key substrate. Understanding these underlying mechanisms provides key insights that could potentially impact the diagnosis, clinical monitoring, nutrition, and therapy of patients suffering from this deadly disease.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, 4918B TVC, 1301 Medical Center Dr., Nashville, TN 37027, USA. adam.seegmiller@vanderbilt.edu.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Seegmiller
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction
chemical_list: D005231:Fatty Acids, Unsaturated; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D044943:Fatty Acid Desaturases; D055372:AMP-Activated Protein Kinases