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Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V\u2010shaped glutamyl\u2010tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the \u201cRadical SAM enzyme\u201d coproporphyrinogen III dehydrogenase. 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