Research

1. Lipid Mediator Biosynthesis: mechanisms of oxygenation of polyunsaturated fatty acids

**Hydrogen Abstraction and Oxygenation in Different Classes of Fatty Acid Oxygenase** *Top, left side*: Lipoxygenase (LOX) and Cyclooxygenase (COX) enzymes initiate catalysis with a hydrogen abstraction then molecular oxygen reacts on the opposite face of the substrate. *Top, right side*: Cytochrome P450s abstract the hydrogen and oxygen reacts on the same face of the substrate. *Below, left and right*: The relationship of R and S chirality of oxygenations in linoleic acid and arachidonic acid.

2. Role of the 12R-Lipoxygenase Pathway in Skin Barrier Formation

LOX action in the mammalian epidermis: CerEOS to ox-CerEOS to bound CerOS. Oxidation of CerEOS containing esterified linoleic acid is initiated by 12R-LOX and its 9-hydroperoxy product is isomerized by Epidermal Lipoxygenase-3 (eLOX3) to form the epoxy-hydroxy product illustrated above. How this leads eventually to covalent binding of the ceramide is under investigation. Our 2019/2020 paper in the Journal of Clinical Investigation reports a new step in the pathway involving the short-chain dehydrogenase/reductase SDR9C7.