Hermann-Georg Holzhütter

Abstract Arachidonic acid lipoxygenases (ALOX-isoforms) have been implicated in cell differentiation and in the pathogenesis of various diseases. Human ALOX-isoforms prefer free polyunsaturated fatty acids as substrate but some of them are also capable of oxygenating complex ester lipids. Here we compared the reactivity of mammalian ALOX isoforms with complex lipid structures, explored the chemistry of the oxygenation products and characterized the structure of the enzyme-substrate complexes.

(p)LD(s) (potential) lipid droplet(s) CPE cholesteryl palmitate ester DGAT diglyceride acyltransferase ER endoplasmic reticulum FA(s) fatty acid(s) GUV(s) giant unilamellar vesicle(s) MD molecular dynamics PC phosphatidylcholine PL(s) phospholipid(s) TAG triacylglycerol VLDL very low-density lipoprotein Introduction Fatty acids (FAs) are important substrates for the synthesis of cellular membranes and energy (ATP). FAs are very poorly soluble in water and cytotoxic even in low concentrations.