The lipid metabolism of blood and culture forms of Trypanosoma lewisi and Trypanosoma rhodesiense

Dixon, Honor; Ginger, Colin D.; Williamson, J.

doi:10.1016/0305-0491(71)90168-4

Cited by 44 publications

(35 citation statements)

References 26 publications

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“…In fact, for many years it was thought that BSFs could not make fatty acids at all (9). More recently, however, our laboratory reported robust in vitro fatty acid synthesis (FAS) activity using BSF membranes as the source of enzymes (10).…”

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confidence: 99%

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Stephens¹,

Lee²,

Paul³

et al. 2007

Journal of Biological Chemistry

111

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Whereas other organisms utilize type I or type II synthases to make fatty acids, trypanosomatid parasites such as Trypanosoma brucei are unique in their use of a microsomal elongase pathway (ELO) for de novo fatty acid synthesis (FAS). Because of the unusual lipid metabolism of the trypanosome, it was important to study a second FAS pathway predicted by the genome to be a type II synthase. We localized this pathway to the mitochondrion, and RNA interference (RNAi) or genomic deletion of acyl carrier protein (ACP) and ␤-ketoacyl-ACP synthase indicated that this pathway is likely essential for bloodstream and procyclic life cycle stages of the parasite. In vitro assays show that the largest major fatty acid product of the pathway is C16, whereas the ELO pathway, utilizing ELOs 1, 2, and 3, synthesizes up to C18. To demonstrate mitochondrial FAS in vivo, we radiolabeled fatty acids in cultured procyclic parasites with

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confidence: 99%

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Stephens¹,

Lee²,

Paul³

et al. 2007

Journal of Biological Chemistry

111

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“…African bloodstream-form trypanosomes are single-celled parasites that appear not to synthesize fatty acids de novo (1)(2)(3), with the exception of myristate ([ 14 C]fatty acid). Trypanosomes have an atypical type II fatty acid synthase that utilizes exogenously supplied butyrate to generate myristate, which is used exclusively for glycosylphosphatidylinositol anchor biosynthesis (4,5).…”

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confidence: 99%

“…Delipidation of the lipoproteins abrogates their capacity to support trypanosome growth. Both major classes of serum lipoproteins, LDL 1 and HDL, are primary sources of lipids, delivering cholesterol esters, cholesterol and phospholipids to trypanosomes (12,13).…”

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confidence: 99%

Evidence for a Trypanosoma brucei Lipoprotein Scavenger Receptor

Green

Portela

Jean

et al. 2003

Journal of Biological Chemistry

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African trypanosomes are lipid auxotrophs that live in the bloodstream of their human and animal hosts. Trypanosomes require lipoproteins in addition to other serum components in order to multiply under axenic culture conditions. Delipidation of the lipoproteins abrogates their capacity to support trypanosome growth. Both major classes of serum lipoproteins, LDL and HDL, are primary sources of lipids, delivering cholesterol esters, cholesterol, and phospholipids to trypanosomes. We show evidence for the existence of a trypanosome lipoprotein scavenger receptor, which facilitates the endocytosis of both native and modified lipoproteins, including HDL and LDL. This lipoprotein scavenger receptor also exhibits selective lipid uptake, whereby the uptake of the lipid components of the lipoprotein exceeds that of the protein components. Trypanosome lytic factor (TLF1), an unusual HDL found in human serum that protects from infection by lysing Trypanosoma brucei brucei, is also bound and endocytosed by this lipoprotein scavenger receptor. HDL and LDL compete for the binding and uptake of TLF1 and thereby attenuate the trypanosome lysis mediated by TLF1. We also show that a mammalian scavenger receptor facilitates lipid uptake from TLF1 in a manner similar to the trypanosome scavenger receptor. Based on these results we propose that HDL, LDL, and TLF1 are all bound and taken up by a lipoprotein scavenger receptor, which may constitute the parasite's major pathway mediating the uptake of essential lipids.

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“…The intermediary metabolism of trypanosomes is highly simplified. Mitochondria1 biogenesis is repressed [43], nearly all Krebs-cycle enzymes are absent [44] and oxidative metabolism of amino acids [45] and fatty acids [46] has not been detected. The only major pathway present is a slightly modified form of glycolysis [47] in which the reduced NAD produced is reoxidized under aerobic conditions by a dihydroxyacetone phosphate : glycerol-3-phosphate cycle.…”

Section: N a D -Linked Glycerol-3-phosphate Dehydrogenasementioning

confidence: 99%

Localization of Glycerol‐3‐Phosphate Oxidase in the Mitochondrion and Particulate NAD⁺‐Linked Glycerol‐3‐Phosphate Dehydrogenase in the Microbodies of the Bloodstream Form of Trypanosoma brucei

Opperdoes

Borst

Bakker

et al. 1977

European Journal of Biochemistry

125

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We have studied the intracellular location of glycerol-3-phosphate oxidase and NAD+-linked glycerol-3-phosphate dehydrogenase, two enzymes involved in the very active dihydroxyacetone phosphate : glycerol-3-phosphate cycle in Trypanosoma brucei. Isopycnic centrifugation of a largegranule fraction resulted in a 10-20-fold purification of the oxidase and showed that the enzyme behaved like the mitochondrial ATPase, isocitrate dehydrogenase and the particulate malate dehydrogenase. The activity profiles of these four enzymes in sucrose gradients were identical with maximal activity at a density of 1.17 g/cm3. Electron micrographs of a fraction equilibrating at this density only showed mitochondrial profiles.The particle-bound NAD+-linked glycerol-3-phosphate dehydrogenase activity was found to band at a density of 1.23 g/cm3 in sucrose. A fraction equilibrating at this density was highly enriched in microbodies; it contained few mitochondrial profiles and less than 3 % of the specific oxidase activity of the mitochondrial fraction. Because of the absence of microbody markers in T. brucei we turned to the insect trypanosome Crithidia luciliae, which contains a high activity of the microbody marker catalase. In C. luciliae part of the catalase activity bands at the same density as the particle-bound NAD +-linked glycerol-3-phosphate dehydrogenase (@ = 1.26 g/cm3).From these results we conclude that in T. brucei bloodstream forms glycerol-3-phosphate oxidase is located in the mitochondrion and not in the microbodies, as proposed by a number of other investigators, and that the particle-bound NAD+-linked glycerol-3-phosphate dehydrogenase is located within the microbodies. It is likely that this highly active dehydrogenase plays an essential role in glycolysis.

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The lipid metabolism of blood and culture forms of Trypanosoma lewisi and Trypanosoma rhodesiense

Cited by 44 publications

References 26 publications

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Evidence for a Trypanosoma brucei Lipoprotein Scavenger Receptor

Localization of Glycerol‐3‐Phosphate Oxidase in the Mitochondrion and Particulate NAD⁺‐Linked Glycerol‐3‐Phosphate Dehydrogenase in the Microbodies of the Bloodstream Form of Trypanosoma brucei

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The lipid metabolism of blood and culture forms of Trypanosoma lewisi and Trypanosoma rhodesiense

Cited by 44 publications

References 26 publications

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Mitochondrial Fatty Acid Synthesis in Trypanosoma brucei

Evidence for a Trypanosoma brucei Lipoprotein Scavenger Receptor

Localization of Glycerol‐3‐Phosphate Oxidase in the Mitochondrion and Particulate NAD+‐Linked Glycerol‐3‐Phosphate Dehydrogenase in the Microbodies of the Bloodstream Form of Trypanosoma brucei

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Localization of Glycerol‐3‐Phosphate Oxidase in the Mitochondrion and Particulate NAD⁺‐Linked Glycerol‐3‐Phosphate Dehydrogenase in the Microbodies of the Bloodstream Form of Trypanosoma brucei