scholarly journals De novo biosynthesis of linoleic acid is widespread in parasitic wasps

2021 ◽  
Author(s):  
Bastian Broschwitz ◽  
Lorena Prager ◽  
Tamara Pokorny ◽  
Joachim Ruther
Keyword(s):  
Linoleic Acid ◽  
De Novo ◽  
Parasitic Wasps ◽  
De Novo Biosynthesis

scholarly journals Parasitic wasps do not lack lipogenesis

2021 ◽  
Author(s):  
Joachim Ruther ◽  
Lorena Prager ◽  
Tamara Pokorny
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Model Organism ◽  
Parasitic Wasps ◽  
Primary Metabolites ◽  
De Novo Biosynthesis ◽  
Fat Reserves ◽  
Lipid Mass ◽  
Unlimited Access ◽  
Eleven Species

Fatty acids are crucial primary metabolites for virtually any creature on earth. Therefore, most organisms do not rely exclusively on nutritional supply with fatty acids but have the ability to synthesize fatty acids and triacylglycerides de novo from carbohydrates, a process called lipogenesis. The ubiquity of lipogenesis has been questioned by a series of studies reporting that many parasitic wasps (parasitoids) do not accumulate lipid mass despite having unlimited access to sugar. This has been interpreted as an evolutionary metabolic trait loss in parasitoids. Here, we demonstrate de novo biosynthesis of fatty acids from 13C-labeled α-D-glucose in eleven species of parasitoids from six families. We furthermore show with the model organism Nasonia vitripennis that lipogenesis occurs even when lipid reserves are still intact, but relative 13C-incorporation rates increase in females with widely depleted fat reserves. Therefore, we conclude that the presumed "lack of lipogenesis" in parasitoids needs to be re-evaluated.

scholarly journals Parasitic wasps do not lack lipogenesis

2021 ◽  
Vol 288 (1951) ◽  
pp. 20210548
Author(s):  
Joachim Ruther ◽  
Lorena Prager ◽  
Tamara Pokorny
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Model Organism ◽  
Parasitic Wasps ◽  
Nasonia Vitripennis ◽  
Primary Metabolites ◽  
De Novo Biosynthesis ◽  
Fat Reserves ◽  
Lipid Mass ◽  
Unlimited Access

Fatty acids are crucial primary metabolites for virtually all creatures on earth. Most organisms thus do not rely exclusively on a nutritional supply containing fatty acids, but have the ability to synthesize fatty acids and triacylglycerides de novo from carbohydrates in a process called lipogenesis. The ubiquity of lipogenesis has been questioned by a series of studies reporting that many parasitic wasps (parasitoids) do not accumulate lipid mass despite having unlimited access to sugar. This has been interpreted as an evolutionary metabolic trait loss in parasitoids. Here, we demonstrate de novo biosynthesis of fatty acids from 13 C-labelled α- d -glucose in 13 species of parasitoids from seven families. We furthermore show in the model organism Nasonia vitripennis that lipogenesis occurs even when lipid reserves are still intact, but relative 13 C-incorporation rates increase in females with widely depleted fat reserves. We therefore conclude that the presumed ‘lack of lipogenesis' in parasitoids needs to be re-evaluated.

De novo biosynthesis of linoleic acid in insects

1986 ◽  
Vol 876 (3) ◽  
pp. 572-580 ◽  
Author(s):  
Colleen Cripps ◽  
Gary J. Blomquist ◽  
Mertxe de Renobales
Keyword(s):  
Linoleic Acid ◽  
De Novo ◽  
De Novo Biosynthesis

scholarly journals On the mechanism of the increase in cardiolipin biosynthesis and resynthesis in hepatocytes during rat liver regeneration

2005 ◽  
Vol 386 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Jennifer WEBSTER ◽  
Jenny Y. JIANG ◽  
Biao LU ◽  
Fred Y. XU ◽  
William A. TAYLOR ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Liver Regeneration ◽  
Rat Liver ◽  
De Novo ◽  
Fold Increase ◽  
Enzymic Activity ◽  
Pool Size ◽  
De Novo Biosynthesis ◽  
Key Enzyme ◽  
Rate Limiting

CL (cardiolipin) is a major mitochondrial membrane phospholipid important for the regulation of mitochondrial function. We examined CL de novo biosynthesis and its resynthesis in isolated rat liver hepatocytes prepared 48 h subsequent to two-thirds PHx (partial hepatectomy). The pool size of CL and its de novo biosynthesis from [1,3-3H]glycerol were increased 3.3-fold (P<0.05) and 3.1-fold (P<0.05) respectively in hepatocytes prepared from PHx rats compared with sham-operated controls. The reason for the increased CL biosynthesis was a 65% increase (P<0.05) in enzymic activity in PGP-S (phosphatidylglycerolphosphate synthase), a key enzyme in de novo CL biosynthesis. The increase in PGP-S activity was due to a 3-fold increase (P<0.05) of hepatic PGP-S mRNA expression. The increase in de novo CL biosynthesis and pool size corresponded to a 2.3-fold increase (P<0.05) in the amount of [1-14C]linoleic acid incorporated into CL of hepatocytes prepared from PHx rats compared with sham-operated controls, indicating an increase in CL resynthesis. The activity of MLCL-AT (monolysocardiolipin acyltransferase), a rate-limiting enzyme of CL resynthesis, was increased by 43% (P<0.05) in hepatocytes prepared from PHx rats compared with sham-operated controls; this result would explain the increase in [1-14C]linoleic acid incorporation into CL. The increase in MLCL-AT activity was due to an increase in hepatic MLCL-AT protein expression. The results show that CL de novo biosynthesis and its resynthesis are increased during liver regeneration.

scholarly journals Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

2021 ◽  
Vol 22 (13) ◽  
pp. 7236
Author(s):  
Endah Dwi Hartuti ◽  
Takaya Sakura ◽  
Mohammed S. O. Tagod ◽  
Eri Yoshida ◽  
Xinying Wang ◽  
...  
Keyword(s):  
Drug Target ◽  
De Novo ◽  
Dihydroorotate Dehydrogenase ◽  
Chemical Library ◽  
New Class ◽  
De Novo Biosynthesis ◽  
Starting Point ◽  
Novel Drugs ◽  
Low Toxicity ◽  
Fourth Step

Plasmodium falciparum’s resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.

scholarly journals De novo Neurosteroidogenesis in Human Microglia: Involvement of the 18 kDa Translocator Protein

2021 ◽  
Vol 22 (6) ◽  
pp. 3115
Author(s):  
Lorenzo Germelli ◽  
Eleonora Da Pozzo ◽  
Chiara Giacomelli ◽  
Chiara Tremolanti ◽  
Laura Marchetti ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
De Novo ◽  
Neuroactive Steroids ◽  
Translocator Protein ◽  
Compensatory Mechanism ◽  
Human Microglia ◽  
De Novo Biosynthesis ◽  
Murine Microglia ◽  
Synthetic Ligand ◽  
Tspo Expression

Neuroactive steroids are potent modulators of microglial functions and are capable of counteracting their excessive reactivity. This action has mainly been ascribed to neuroactive steroids released from other sources, as microglia have been defined unable to produce neurosteroids de novo. Unexpectedly, immortalized murine microglia recently exhibited this de novo biosynthesis; herein, de novo neurosteroidogenesis was characterized in immortalized human microglia. The results demonstrated that C20 and HMC3 microglial cells constitutively express members of the neurosteroidogenesis multiprotein machinery—in particular, the transduceosome members StAR and TSPO, and the enzyme CYP11A1. Moreover, both cell lines produce pregnenolone and transcriptionally express the enzymes involved in neurosteroidogenesis. The high TSPO expression levels observed in microglia prompted us to assess its role in de novo neurosteroidogenesis. TSPO siRNA and TSPO synthetic ligand treatments were used to reduce and prompt TSPO function, respectively. The TSPO expression downregulation compromised the de novo neurosteroidogenesis and led to an increase in StAR expression, probably as a compensatory mechanism. The pharmacological TSPO stimulation the de novo neurosteroidogenesis improved in turn the neurosteroid-mediated release of Brain-Derived Neurotrophic Factor. In conclusion, these results demonstrated that de novo neurosteroidogenesis occurs in human microglia, unravelling a new mechanism potentially useful for future therapeutic purposes.

Sign in / Sign up

Export Citation Format

Share Document