ABSTRACT
This review describes the catalytic mechanism, substrate specificity, and structural peculiarities of alpha-ketoglutarate dependent nonheme iron dioxygenases catalyzing prolyl hydroxylation of hypoxia-inducible factor (HIF). Distinct localization and regulation of three isoforms of HIF prolyl hydroxylases suggest their different roles in cells. The recent identification of novel substrates other than HIF, namely ß2-adrenergic receptor and the large subunit of RNA polymerase II, places these enzymes in the focus of drug development efforts aimed at development of isoform-specific inhibitors. The challenges and prospects of designing isoform-specific inhibitors are discussed.
Subject(s)
Hypoxia-Inducible Factor 1/metabolism , Procollagen-Proline Dioxygenase/metabolism , Catalysis , Drug Design , Hypoxia-Inducible Factor 1/chemistry , Ketoglutaric Acids/chemistry , Ketoglutaric Acids/metabolism , Procollagen-Proline Dioxygenase/chemistry , Protein Isoforms , Substrate SpecificityABSTRACT
A laboratory study was conducted to evaluate the potential for secondary organic aerosol formation from emissions from automotive exhaust. The goal was to determine to what extent photochemical oxidation products of these hydrocarbons contribute to secondary organic aerosol (SOA) and how well their formation is described by recently developed models for SOA formation. The quality of a surrogate was tested by comparing its reactivity with that from irradiations of authentic automobile exhaust. Experiments for secondary particle formation using the surrogate were conducted in a fixed volume reactor operated in a dynamic mode. The mass concentration of the aerosol was determined from measurements of organic carbon collected on quartz filters and was corrected for the presence of hydrogen, nitrogen, and oxygen atoms in the organic species. A functional group analysis of the aerosol made by Fourier transform infrared (FTIR) spectroscopy indicated
