Abstract
Carotenoids are widespread lipophilic pigments synthesized by all photosynthetic organisms and some nonphotosynthetic fungi and bacteria. All carotenoids are derived from the C40 isoprenoid precursor geranylgeranyl pyrophosphate, and their chemical and physical properties are associated with light absorption, free radical scavenging, and antioxidant activity. Carotenoids are generally synthesized in well defined subcellular organelles, the plastids, which are also present in the phylum Apicomplexa, which comprises a number of important human parasites, such as Plasmodium and Toxoplasma. Recently, it was demonstrated that Toxoplasma gondii synthesizes abscisic acid. We therefore asked if Plasmodium falciparum is also capable of synthesizing carotenoids. Herein, biochemical findings demonstrated the presence of carotenoid biosynthesis in the intraerythrocytic stages of the apicomplexan parasite P. falciparum. Using metabolic labeling with radioisotopes, in vitro inhibition tests with norflurazon, a specific inhibitor of plant carotenoid biosynthesis, the results showed that intraerythrocytic stages of P. falciparum synthesize carotenoid compounds. A plasmodial enzyme that presented phytoene synthase activity was also identified and characterized. These findings not only contribute to the current understanding of P. falciparum evolution but shed light on a pathway that could serve as a chemotherapeutic target.
Highlights
Human malaria is caused by four species of the parasitic protozoan genus Plasmodium
Using metabolic labeling with radioisotopes, in vitro inhibition tests with norflurazon, a specific inhibitor of plant carotenoid biosynthesis, the results showed that intraerythrocytic stages of P. falciparum synthesize carotenoid compounds
The carotenoid biosynthesis is an attractive target for investigation, because it is essential in algae, higher plants, bacteria, and fungi but absent in mammals, and its products are involved in many important metabolic functions [7]
Summary
Reagents Percoll was purchased from Amersham Biosciences. [1-3H]Geranylgeranyl pyrophosphate triammonium salt ([1-3H]GGPP) (16.5 Ci/mmol), [1-14C]isopentenyl pyrophosphate ammonium salt (55.0 Ci/mmol) ([14C]IPP), and L-[35S]methionine (Ͼ1,000 Ci/mmol) were obtained from Amersham Biosciences. Reagents Percoll was purchased from Amersham Biosciences. [1-3H]Geranylgeranyl pyrophosphate triammonium salt ([1-3H]GGPP) (16.5 Ci/mmol), [1-14C]isopentenyl pyrophosphate ammonium salt (55.0 Ci/mmol) ([14C]IPP), and L-[35S]methionine (Ͼ1,000 Ci/mmol) were obtained from Amersham Biosciences. Vents used were of HPLC grade or better. (Basel, Switzerland) generously donated the herbicide norflurazon. Authentic standards of dolichol and polyprenol were kindly supplied by Dr Tadeusz Chojnacki (Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, Warsaw, Poland). Lithium iodide hydrate was purchased from Fluka. Sigma provided farnesyl pyrophosphate ammonium salt, geranylgeranyl pyrophosphate ammonium salt, all-trans-lutein, alltrans--carotene, and all other biochemical reagents. Carotenoid standards were donated by DSM Nutritional Products (Basel, Switzerland)
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