title: A heme-degradation pathway in a blood-sucking insect.
abstract: Hematophagous insects are vectors of diseases that affect hundreds of millions of people worldwide. A common physiological event in the life of these insects is the hydrolysis of host hemoglobin in the digestive tract, leading to a massive release of heme, a known prooxidant molecule. Diverse organisms, from bacteria to plants, express the enzyme heme oxygenase, which catalyzes the oxidative degradation of heme to biliverdin (BV) IX, CO, and iron. Here, we show that the kissing bug Rhodnius prolixus, a vector of Chagas' disease, has a unique heme-degradation pathway wherein heme is first modified by addition of two cysteinylglycine residues before cleavage of the porphyrin ring, followed by trimming of the dipeptides. Furthermore, in contrast to most known heme oxygenases, which generate BV IXalpha, in this insect, the end product of heme detoxification is a dicysteinyl-BV IXgamma. Based on these results, we propose a heme metabolizing pathway that includes the identified intermediates produced during modification and cleavage of the heme porphyrin ring.
authors.affiliation: Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, CEP 21941-590, Rio de Janeiro, Brazil.
authors.forename: Gabriela O
authors.initials: GO
authors.lastname: Paiva-Silva
authors.forename: Christine
authors.initials: C
authors.lastname: Cruz-Oliveira
authors.forename: Ernesto S
authors.initials: ES
authors.lastname: Nakayasu
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Maya-Monteiro
authors.forename: Boris C
authors.initials: BC
authors.lastname: Dunkov
authors.forename: Hatisaburo
authors.initials: H
authors.lastname: Masuda
authors.forename: Igor C
authors.initials: IC
authors.lastname: Almeida
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D001664:Biliverdine; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006418:Heme / Q000737:chemistry*; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry; D006868:Hydrolysis; D008956:Models, Chemical; D018384:Oxidative Stress; D011166:Porphyrins / Q000737:chemistry; D012239:Rhodnius / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D011166:Porphyrins; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine