title: Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum.
abstract: All eight enzymes required for de novo heme biosynthesis have been predicted from the nuclear genome of the human malaria parasite Plasmodium falciparum. We have studied the subcellular localization of three of these using a GFP reporter in live transfected parasites. The first enzyme in the pathway delta-aminolevulinic acid synthase (ALAS) is targeted to the mitochondrion, but the next two enzymes porphobilinogen synthase (PBGS) and hydroxymethylbilane synthase (HMBS) are targeted to the plastid. An enzymatically active recombinant version of PBGS from P. falciparum was over-expressed and its activity found to be stimulated by Mg2+ (and enhanced by Mn2+) but not by Zn2+. A hypothetical scheme for the exchange of intermediates in heme biosynthesis between the mitochondrion and plastid organelle, as well as organelle attachment is discussed.
authors.affiliation: National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. ssato@nimr.mrc.ac.uk
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Sato
authors.forename: Barbara
authors.initials: B
authors.lastname: Clough
authors.forename: Leighton
authors.initials: L
authors.lastname: Coates
authors.forename: R J M
authors.initials: RJ
authors.lastname: Wilson
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000032:analysis; D000818:Animals; D019677:Artificial Gene Fusion; D003067:Coenzymes / Q000494:pharmacology; D017930:Genes, Reporter; D006418:Heme / Q000096:biosynthesis*; D011163:Hydroxymethylbilane Synthase / Q000032:analysis; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D018087:Plastids / Q000201:enzymology* / Q000235:genetics; D000623:Porphobilinogen Synthase / Q000032:analysis; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
chemical_list: D003067:Coenzymes; D008670:Metals; D011994:Recombinant Proteins; D006418:Heme; D008345:Manganese; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D000623:Porphobilinogen Synthase; D008274:Magnesium; D015032:Zinc