Defective degradation of leukotrienes in peroxisomal-deficient human hepatocytes.
Chain-shortening via beta-oxidation from the omega-end has been recognized as the major pathway for the degradation of the biologically active cysteinyl leukotrienes as well as LTB4. The metabolic compartmentation of this pathway was investigated in peroxisomal-deficient (Zellweger syndrome) and normal human hepatocytes. Leukotriene metabolism was studied in isolated hepatocytes by incubation with omega-carboxy-[3H]LTE4 as well as omega-carboxy-[3H]LTB4. Analysis was done by HPLC, UV-detection and radioactivity measurements. Incubation of normal hepatocytes with omega-carboxy-[3H]LTE4 or omega-carboxy-[3H]LTB4 resulted in the formation of the corresponding beta-oxidation products, whereas beta-oxidation derivatives were not detected as products formed by peroxisome-deficient human hepatocytes. These results underline the essential contribution of peroxisomes in the catabolism and inactivation of cysteinyl leukotrienes and LTB4 in humans.
Mayatepek
E
E
Division of Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
Tiepelmann
B
B
D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008830:Microbodies; D010084:Oxidation-Reduction; D015211:Zellweger Syndrome / Q000378:metabolism*
D015289:Leukotrienes