INCORPORATION OF RADIOACTIVE COMPOUNDS INTO THE PURINE AND PYRIMIDINE BASES AND 2-DEOXYRIBOSE OF SALMON TESTES DEOXYRIBONUCLEIC ACID

1966 ◽  
Vol 44 (11) ◽  
pp. 1435-1446 ◽  
Author(s):  
H. L. A. Tars ◽  
Joan Roy
Keyword(s):  
Deoxyribonucleic Acid ◽  
De Novo ◽  
Biosynthetic Pathways ◽  
De Novo Biosynthesis ◽  
Adenylic Acid ◽  
Pyrimidine Bases ◽  
Purines And Pyrimidines

Slices of immature salmon testes incorporated radioactive purine and pyrimidine bases and related nucleosides, deoxynucleosides, nucleotides, and deoxynucleotides into deoxyribonucleic acid (DNA). When DNA was extracted from the tissues and hydrolyzed, the purine and pyrimidine bases obtained were labeled in a manner which suggested that the radioactive substrates had been incorporated into DNA by recognized biosynthetic pathways involving "preformed" purines and pyrimidines and their derivatives. Since radioactive carbonate, glycine, and formate were not incorporated into the purines obtained from DNA, and radioactive formate only caused labeling of the thymine, it would appear unlikely that the de novo biosynthesis of purine and pyrimidine rings occurs in milts. C-1, C-6, and generally labeled glucose-14C caused labeling of the 2-deoxyribose, but not of the purines or pyrimidines, of DNA. Radioactive adenylic acid, deoxyuridylic acid, ribose 5-phosphate, and 5-phospho-α-D-ribofuranosyl-1-pyrophosphate also caused labeling of the 2-deoxyribose of DNA.

EFFECTS OF DIETETIC NUCLEIC ACIDS AND COMPONENTS ON GROWTH OF AGRIA AFFINIS (FALLÉN) (DIPTERA: SARCOPHAGIDAE)

1964 ◽  
Vol 42 (5) ◽  
pp. 801-806 ◽  
Author(s):  
H. L. House
Keyword(s):  
Nucleic Acids ◽  
Growth Rates ◽  
Deoxyribonucleic Acid ◽  
Optimal Growth ◽  
Insect Larvae ◽  
Ecological Adaptations ◽  
Adenylic Acid ◽  
Pyrimidine Bases ◽  
Derivatives Of ◽  
Respective Species

Feeding tests on chemically defined diets; showed that dietary nucleic acids are needed for optimal growth rates of the parasitoid Agria affinis (Fallén) reared axenically. Both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) met this requirement qualitatively and were almost equal quantitatively. The nucleotides adenylic acid, guanylic acid, cytidylic acid, and uridylic acid were the only derivatives of RNA used by the insect larvae to promote growth rates. These nucleotides were equally well utilized regardless of whether their base was purine or pyrimidine. No evidence was found for the utilization of single nucleosides or purine and pyrimidine bases. Phosphorylation of the molecule seemed to be the primary need that decided the utilization of dietary nucleic acid components in this species of Diptera. This augments evidence that various species of Diptera utilize nucleic acids and their derivatives differently. Moreover, it supports an attractive hypothesis of other workers that differences in utilization derive from ecological adaptations of the respective species and more greatly concern the needs for non-essential nutrients than for the essential ones.

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.

scholarly journals Dietary Essential Amino Acid Restriction Promotes Hyperdipsia via Hepatic FGF21

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1469
Author(s):  
Patricia M. Rusu ◽  
Andrea Y. Chan ◽  
Mathias Heikenwalder ◽  
Oliver J. Müller ◽  
Adam J. Rose
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Dietary Protein ◽  
Essential Amino Acid ◽  
De Novo ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
De Novo Biosynthesis ◽  
Dietary Requirements ◽  
Dietary Amino Acid

Prior studies have reported that dietary protein dilution (DPD) or amino acid dilution promotes heightened water intake (i.e., hyperdipsia) however, the exact dietary requirements and the mechanism responsible for this effect are still unknown. Here, we show that dietary amino acid (AA) restriction is sufficient and required to drive hyperdipsia during DPD. Our studies demonstrate that particularly dietary essential AA (EAA) restriction, but not non-EAA, is responsible for the hyperdipsic effect of total dietary AA restriction (DAR). Additionally, by using diets with varying amounts of individual EAA under constant total AA supply, we demonstrate that restriction of threonine (Thr) or tryptophan (Trp) is mandatory and sufficient for the effects of DAR on hyperdipsia and that liver-derived fibroblast growth factor 21 (FGF21) is required for this hyperdipsic effect. Strikingly, artificially introducing Thr de novo biosynthesis in hepatocytes reversed hyperdipsia during DAR. In summary, our results show that the DPD effects on hyperdipsia are induced by the deprivation of Thr and Trp, and in turn, via liver/hepatocyte-derived FGF21.

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
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