Acetate formation in the energy metabolism of parasitic helminths and protists

Tielens, Aloysius G.M.; Grinsven, Koen W.A. van; Henze, Katrin; Hellemond, Jaap J. van; Martin, William

doi:10.1016/j.ijpara.2009.12.006

Cited by 101 publications

(109 citation statements)

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“…ASCTs were only recently characterized for eukaryotes, and it was shown that these enzymes are family I-type CoA-transferases, where ASCT is only one member of a multitude of different acetate-producing enzymes in eukaryotes (reviewed in reference 503). The ASCT in anaerobically functioning Fasciola mitochondria is closely related to the CoAtransferases of bacteria such as Roseburia and to that of Artemia franciscana, a brine shrimp, and these enzymes all belong to subfamily 1B of the CoA-transferases (503,528). Succinyl-CoA synthetase (SCS) (also called succinate thiokinase and abbreviated STK in many papers), a canonical Krebs cycle enzyme (93), conserves the energy in the thioester bond of succinyl-CoA by ATP synthesis from succinyl-CoA, ADP, and P i via substrate-level phosphorylation involving succinyl phosphate as a reaction mechanism intermediate (197), regenerating CoA for the PDH reaction and succinate for the ASCT reaction.…”

Section: Animalsmentioning

confidence: 99%

“…The resulting acetyl-CoA is then converted into a mixture of acetate, which allows the synthesis of one additional ATP per pyruvate, and ethanol, which allows the regeneration of NAD ϩ , depending upon the redox state of the cell. The acetate-generating enzyme of Entamoeba, acetylCoA synthase (ADP forming), is a comparatively rare enzyme among eukaryotes (503), but the same enzyme is used in the core energy metabolism of Giardia intestinalis (428), and homologs occur in the genome of the diatom Thalassiosira pseudonana, in apicomplexan genomes (several Plasmodium species and Cryptosporidium muris), in the stramenopile Blastocystis hominis, and in the excavate taxon Naegleria gruberi (371). The ethanol-generating enzyme is a bifunctional aldehyde/alcohol dehydrogenase (ADHE), a fusion protein consisting of an N-terminal aldehyde dehydrogenase (ALDH) (acetylating) domain and a C-terminal alcohol dehydrogenase (ADH) domain (138).…”

Section: Amoebozoa: Entamoeba Histolyticamentioning

confidence: 99%

“…The acetate-generating enzyme of hydrogenosomes, ASCT, which was originally described for Trichomonas (277), was only recently characterized at the molec-ular level (529). The Trichomonas ASCT enzyme is distinct from the ASCT enzyme that generates acetate as an end product in trypanosome mitochondria (503,528,533).…”

Section: Fig 11mentioning

confidence: 99%

“…Consequently, pyruvate is not completely oxidized to carbon dioxide by Krebs cycle activity but instead is converted mainly into acetate. Acetate production from acetyl-CoA occurs mainly by a two-enzyme cycle, in which ASCT transfers the CoA moiety of acetyl-CoA to succinate, yielding acetate and succinyl-CoA, which is subsequently converted by SCS with the concomitant production of ATP (53,503,413,533). The T. brucei ASCT enzyme is not homologous to the ASCT enzymes used by Trichomonas vaginalis hydrogenosomes and Fasciola hepatica mitochondria (503).…”

Section: Fig 13mentioning

confidence: 99%

“…Acetate production from acetyl-CoA occurs mainly by a two-enzyme cycle, in which ASCT transfers the CoA moiety of acetyl-CoA to succinate, yielding acetate and succinyl-CoA, which is subsequently converted by SCS with the concomitant production of ATP (53,503,413,533). The T. brucei ASCT enzyme is not homologous to the ASCT enzymes used by Trichomonas vaginalis hydrogenosomes and Fasciola hepatica mitochondria (503). Although the ASCT gene is not an essential gene, because an alternative acetate-producing pathway exists, the importance of ASCT for the normal physiological phenotype of the parasite has been clearly shown (413).…”

Section: Fig 13mentioning

confidence: 99%

See 4 more Smart Citations

Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

Müller

Mentel

Hellemond

et al. 2012

Microbiol Mol Biol Rev

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684

904

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SUMMARY Major insights into the phylogenetic distribution, biochemistry, and evolutionary significance of organelles involved in ATP synthesis (energy metabolism) in eukaryotes that thrive in anaerobic environments for all or part of their life cycles have accrued in recent years. All known eukaryotic groups possess an organelle of mitochondrial origin, mapping the origin of mitochondria to the eukaryotic common ancestor, and genome sequence data are rapidly accumulating for eukaryotes that possess anaerobic mitochondria, hydrogenosomes, or mitosomes. Here we review the available biochemical data on the enzymes and pathways that eukaryotes use in anaerobic energy metabolism and summarize the metabolic end products that they generate in their anaerobic habitats, focusing on the biochemical roles that their mitochondria play in anaerobic ATP synthesis. We present metabolic maps of compartmentalized energy metabolism for 16 well-studied species. There are currently no enzymes of core anaerobic energy metabolism that are specific to any of the six eukaryotic supergroup lineages; genes present in one supergroup are also found in at least one other supergroup. The gene distribution across lineages thus reflects the presence of anaerobic energy metabolism in the eukaryote common ancestor and differential loss during the specialization of some lineages to oxic niches, just as oxphos capabilities have been differentially lost in specialization to anoxic niches and the parasitic life-style. Some facultative anaerobes have retained both aerobic and anaerobic pathways. Diversified eukaryotic lineages have retained the same enzymes of anaerobic ATP synthesis, in line with geochemical data indicating low environmental oxygen levels while eukaryotes arose and diversified.

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Section: Animalsmentioning

confidence: 99%

Section: Amoebozoa: Entamoeba Histolyticamentioning

confidence: 99%

Section: Fig 11mentioning

confidence: 99%

Section: Fig 13mentioning

confidence: 99%

Section: Fig 13mentioning

confidence: 99%

See 3 more Smart Citations

Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

Müller

Mentel

Hellemond

et al. 2012

Microbiol Mol Biol Rev

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684

904

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Redefining the coenzyme A transferase superfamily with a large set of manually annotated proteins

Hackmann

2022

Protein Science

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The coenzyme A (CoA) transferases are a superfamily of proteins central to the metabolism of acetyl-CoA and other CoA thioesters. They are diverse group, catalyzing over a 100 biochemical reactions and spanning all three domains of life. A deeply rooted idea, proposed two decades ago, is these enzymes fall into three families (I, II, and III). Here we find they fall into different families, which we achieve by analyzing all CoA transferases characterized to date. We manually annotated 94 CoA transferases with functional information (including rates of catalysis for 208 reactions) from 97 publications. This represents all enzymes we could find in the primary literature, and it is double the number annotated in four protein databases (BRENDA, KEGG, MetaCyc, UniProt). We found family I transferases are not closely related to each other in terms of sequence, structure, and reactions catalyzed. This family is not even monophyletic. These problems are solved by regrouping the three families into six, including one family with many non-CoA transferases. The problem (and solution) became apparent only by analyzing our large set of manually annotated proteins. It would have been missed if we had used the small number of proteins annotated in UniProt and other databases. Our work is important to understanding the biology of CoA transferases. It also warns investigators doing phylogenetic analyses of proteins to go beyond information in databases.

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Mitochondrion-Related Organelles in Free-Living Protists

Leger

Kolísko

Stairs

et al. 2019

Microbiology Monographs

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Mitochondrion-related organelles (MROs) are a set of functionally diverse organelles that have independently evolved from mitochondria in eukaryotes that live in low-oxygen conditions. These organelles are functionally diverse, possessing a range of ancestrally mitochondrial or horizontally-acquired biochemical pathways. Early studies of MROs focused mainly on parasitic organisms; however, the past decade has seen a growing body of work on the MROs of free-living eukaryotes based on comparative genomics, making it possible to tease apart adaptations to low-oxygen conditions from adaptations to parasitism. Here, we review current knowledge of MROs in free-living eukaryotes. 2

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Acetate formation in the energy metabolism of parasitic helminths and protists

Cited by 101 publications

References 94 publications

Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

Redefining the coenzyme A transferase superfamily with a large set of manually annotated proteins

Mitochondrion-Related Organelles in Free-Living Protists

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