Oxidation of 7,8-dihydroneopterin by hypochlorous acid yields neopterin

In vitro, interferon-gamma stimulates primate monocytes/macrophages to prod uce the pteridines neopterin and 7,8-dihydroneopterin. These pteridines are capable of modulating the oxidative potential of reactive species. Neopter in is pro-oxidative whereas 7,8-dihydroneopterin is an effective antioxidan t. In the presence of oxygen, 7,8-dihydroneopterin is rapidly oxidized and after loosing the side chain 7,8-dihydroxanthopterin is formed. It is consi dered that under physiological conditions, 7,8-dihydroneopterin cannot be a source for neopterin production. In this study it is demonstrated that hyp ochlorous acid is capable to oxidize 7,8-dihydroneopterin yielding neopteri n. Neopterin is less affected by hypochlorous acid, and in a mixture of bot h pteridines similar to the in vivo situation, only 7,8-dihydroneopterin is oxidized, thereby increasing the ratio towards neopterin. The findings may beat relevance for the in vivo situation since hypochlorous acid shifts th e neopterin/7,8-dihydroneopterin ratio towards the side of neopterin, hence probably increasing the oxidative potential in a micro-environment. (C) 20 00 Academic Press.