Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has the nitrogen atoms at positions 1 and 3 in the ring. 65-86-1, formula is C5H4N2O4, Name is 2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Electric Literature of 65-86-1.
Souders, Christopher L. II;Sanchez, Christina L.;Malphurs, Wendi;Aristizabal-Henao, Juan J.;Bowden, John A.;Martyniuk, Christopher J. research published 《 Metabolic profiling in human SH-SY5Y neuronal cells exposed to perfluorooctanoic acid (PFOA)》, the research content is summarized as follows. Perfluorooctanoic acid (PFOA) is an abundant per- and polyfluoroalkyl substance (PFAS) detected in both indoor and outdoor environments. While studies suggest exposure concerns for humans, studies investigating PFOA-induced neurotoxicity are lacking. To address this gap, we exposed differentiated human SH-SY5Y cells to PFOA (0.1μM up to 500μM) at different time points (4, 24, 48, and 72 h) and measured cell viability, Casp3/7 activity, ATP levels, ATP synthase enzyme activity, mitochondrial membrane potential, reactive oxygen species (ROS), oxygen consumption rates for mitochondrial stress test (XFe24 Flux analyzer), glucose utilization, and global metabolome profiles to assess the potential for PFOA-induced neurotoxicity. Treatment with 10 or 100μM PFOA did not compromise cell viability nor induce cytotoxicity to SH-SY5Y cells over a 48-h exposure period. However, >250μM PFOA compromised cell viability, induced cytotoxicity, and induced caspase 3/7 activity at 48 h. ATP levels were reduced in cells treated with 400μM PFOA for 24 and 48 h, and with 100μM PFOA and higher at 72 h. ATP synthase activity was inhibited by 250μM PFOA but was unchanged by PFOA treatment at 200μM or less. Conversely, mitochondrial membrane potential was reduced by >10μM PFOA after 24 h. Total ROS was increased with 100μM PFOA and higher after 4 h of exposure. Several mitochondria-related endpoints (basal respiration, ATP production, maximum respiration) were neg. affected at 250μM PFOA at both 24- and 48-h exposure, but were unaltered at concentrations of 100μM PFOA or less. One exception was mitochondrial spare capacity, which was reduced by 100μM PFOA after 24-h exposure. Similarly, glycolysis, glycolytic capacity, and glycolytic reserve of SH-SY5Y cells were not altered by 10 nor 100μM PFOA. Nontargeted metabolomics was conducted in cells treated with either 10 or 100μM PFOA for 48 h, as these two concentrations were not cytotoxic and 28 metabolites differed among treatments. Notable was that 10μM PFOA had little effect on the SH-SY5Y metabolome, and the metabolic profile was not statistically different from media nor solvent controls. On the other hand, 100μM PFOA shifted the metabolic signature of the neuronal cells, leading to reduced abundance of ATP-related metabolites (adenine, nicotinamide), neurotransmitter precursors (DL-tryptophan, L-tyrosine), and metabolites that protect mitochondria during oxidative stress (betaine, orotic acid, and L-acetyl carnitine). We hypothesize that this metabolic signature may be associated with the reduced mitochondrial membrane potential observed at lower PFOA concentrations Metabolic shifts appear to precede compromised cell viability, cytotoxicity, and apoptosis. This study generates mechanistic knowledge regarding PFOA-induced neurotoxicity, focusing on mitochondrial oxidative respiration and the neuronal metabolome.
Electric Literature of 65-86-1, Orotic acid anhydrous is a hydrogen bonding interaction that can be found in biological systems. It plays a role in the physiological effects of orotic acid, which is a metabolite of uridine and an intermediate in the synthesis of pyrimidine nucleotides. Orotic acid has antimicrobial properties and has been shown to inhibit enzyme activities involved in energy metabolism, such as polymerase chain reaction (PCR) and adenosine triphosphate (ATP) synthase. Orotic acid also inhibits the growth of bacteria, fungi, and parasites. Orotic acid anhydrous is used for treating myocardial infarcts or brain functions. The untreated group was given no treatment at all.
Orotic acid, also known as orotate or orotsaeure, belongs to the class of organic compounds known as pyrimidinecarboxylic acids. These are pyrimidines with a structure containing a carboxyl group attached to the pyrimidine ring. Orotic acid exists as a solid, slightly soluble (in water), and a moderately acidic compound (based on its pKa). Orotic acid has been found in human liver and pancreas tissues, and has also been primarily detected in saliva, feces, urine, and blood. Within the cell, orotic acid is primarily located in the cytoplasm and mitochondria. Orotic acid exists in all eukaryotes, ranging from yeast to humans. Orotic acid participates in a number of enzymatic reactions. In particular, Orotic acid can be biosynthesized from L-dihydroorotic acid and quinone; which is mediated by the enzyme dihydroorotate dehydrogenase (quinone), mitochondrial. In addition, Orotic acid and phosphoribosyl pyrophosphate can be converted into orotidylic acid through its interaction with the enzyme uridine monophosphate synthetase isoform a. In humans, orotic acid is involved in the pyrimidine metabolism pathway. Orotic acid is also involved in several metabolic disorders, some of which include the mngie (mitochondrial neurogastrointestinal encephalopathy) pathway, dihydropyrimidinase deficiency, UMP synthase deficiency (orotic aciduria), and Beta ureidopropionase deficiency. Outside of the human body, orotic acid can be found in a number of food items such as green vegetables, alaska blueberry, chickpea, and colorado pinyon. This makes orotic acid a potential biomarker for the consumption of these food products. Orotic acid is a potentially toxic compound. Orotic acid has been found to be associated with several diseases known as phosphoenolpyruvate carboxykinase deficiency 1, cytosolic and hyperornithinemia-hyperammonemia-homocitrullinuria; orotic acid has also been linked to several inborn metabolic disorders including n-acetylglutamate synthetase deficiency, lysinuric protein intolerance, and ornithine transcarbamylase deficiency.
Orotic acid appears as white crystals or crystalline powder.
Orotic acid is a pyrimidinemonocarboxylic acid that is uracil bearing a carboxy substituent at position C-6. It has a role as a metabolite, an Escherichia coli metabolite and a mouse metabolite. It derives from a uracil. It is a conjugate acid of an orotate., 65-86-1.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia