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If the fatty acid supply of mitochondrial acetyl CoA stops, while the glycolytic supply of acetyl CoA is also closed, the tumor cell mitochondria will have to get their acetyl CoA from ketolysis. Finally, we should point that even with SCOT and ATP citrate lyase inhibition, tumor cells still possess a salvage pathway for making acetyl CoA in the cytosol, from acetate directly taken up and processed by an acetyl CoA synthetase. [Extracted from the article]

Orotic acid (OA) is a natural product that acts as a precursor in the pyrimidine nucleotide biosynthesis pathway. Most studies concerning administration of OA focus on its therapeutic effects; however, its effect on tumours is unclear. We aimed to determine whether treatment with OA influences the viability and apoptosis of normal (HGrC1) and tumour-derived (KGN) human ovarian granulosa cells. The effects of OA (10-250 μM) on viability and apoptosis of both cell lines were determined by using alamarBlue and assessing caspase-3/7 activity, respectively. Annexin V binding and loss of membrane integrity were evaluated in KGN cells. The cell cycle and proliferation of HGrC1 cells were assessed by performing flow cytometric and DNA content analyses, respectively. The influence of OA (10 and 100 μM) on cell cycle- and apoptosis-related gene expression was assessed by RT-qPCR in both cell lines. Mitochondrial activity was analysed by JC-1 staining in HGrC1 cells. In KGN cells, OA reduced viability and increased caspase-3/7 activity, but did not affect mRNA expression of Caspase 3, BAX, and BCL2. OA enhanced proliferation and mitochondrial activity in HGrC1 cells without activating apoptosis. This study demonstrates that the anti-cancer properties of OA in ovarian granulosa tumour cells are not related to changes in apoptosis-associated gene expression, but to increased caspase-3/7 activity. Thus, OA is a promising therapeutic agent for ovarian granulosa tumours. Further, our results suggest that differences in basal expression of cell cycle- and apoptosis-related genes between the two cell lines are responsible for their different responses to OA., Competing Interests: Declaration of Competing Interest The authors declare they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Dietary administration of orotic acid (OA), an intermediate in the pyrimidine biosynthetic pathway, is considered to provide a wide range of beneficial effects, including cardioprotection and exercise adaptation. Its mechanisms of action, when applied extracellularly, however, are barely understood. In this study, we evaluated potential effects of OA on skeletal muscle using an in vitro contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By analyzing a subset of genes representing inflammatory, metabolic, and structural adaptation pathways, we could show that OA supplementation diminishes the EPS-provoked expression of inflammatory transcripts (interleukin 6, Il6; chemokine (C-X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of nuclear receptor subfamily 4 group A member 3 (Nr4A3), early growth response 1 (Egr1), activating transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA isoform (Myh2). By contrast, OA had no suppressive effect on the pathogen-provoked inflammatory gene response in skeletal muscle cells, as demonstrated by stimulation of C2C12 myotubes with bacterial LPS. In addition, we observed a suppressive effect of OA on EPS-induced phosphorylation of AMP-activated protein kinase (AMPK), whereas EPS-triggered phosphorylation/activation of the mammalian target of rapamycin (mTOR) was not affected. Finally, we demonstrate that OA positively influences glycogen levels in EP-stimulated myotubes. Taken together, our results suggest that in skeletal muscle cells, OA modulates both the inflammatory and the metabolic reaction provoked by acute contraction. These results might have important clinical implications, specifically in cardiovascular and exercise medicine. [ABSTRACT FROM AUTHOR]

Cocrystallization of two multifunctional structural isomers viz. orotic and isoorotic acids was explored with a series of amine and pyridine-based coformers. The system has been chosen in such a way so that robustness of the acid…pyridine synthon was tested against competing amine…pyridine and carbonyl…pyridine synthons. Here, we report the structural characterization and solubility measurements of ten solids which include three cocrystals, one salt cocrystal, four salts and two salt hydrates. All multicomponent solids showed significant improvement in solubility in comparison to the acids and also showed a strong correlation between the percentage of the O…H interaction and solubility. The ΔpKa rule is validated in the structural landscape by considering all components of the matrix together. [ABSTRACT FROM AUTHOR]

Computational investigation of orotate phosphoribosyltransferase (OPRT) action, an enzymatic reaction between phosphoribosyl pyrophosphate (PRPP) and orotic acid (OA) to yield orotidine 5′-monophosphate (OMP), was carried out. Insights into the pathways of the substrate attack step of the reaction were developed under the quantum mechanics/molecular mechanics framework with S. cerevisiae strain as the representative enzyme bearer. Four pathways were proposed for PRPP and OA binding differing in the sequence of PRPP, OA and Mg 2+ ion complexation with OPRT. The formation of Mg 2+ -OPRT complex was accompanied by a small energy change while the largest stabilization was observed for the formation of Mg 2+ -PRPP complex supporting the experimental observation of Mg 2+ -PRPP complex as the true substrate for the reaction. Formation of PRPP-OPRT complex was found to be energetically not probable rendering the pathway requiring Mg 2+ -OA complex not probable. Further, PRPP migration towards the active site was found to be energetically not favoured rendering the pathway involving Mg 2+ -OA complexation improbable. Migration of OA and Mg 2+ -PRPP complex towards the active site was found to be energetically probable with a large stabilization of the system when Mg 2+ -PRPP complex bound to the OA-OPRT complex. This conclusively proved the sequential binding of OA and Mg 2+ -PRPP complexes during OPRT action. [ABSTRACT FROM AUTHOR]

The organic acids present in milk in varying quantities can reflect the health condition of the animals and the nutritional quality of milk. In rural areas, goats are maintained in pasture during whole day and milking is being started as soon as goats arrive to farm. However, it is not known whether milking during feeding as soon as goats return from pasture or after 1 hour-waiting have any effect on nitrogen-containing organic acids are the body metabolism products. Therefore, in this study we objected to determine the effects of 1 hour-waiting period before milking on orotic, uric and hippuric acids of milks from "Shami (Damascus)" and "Kilis" goat breeds during lactation period. The trial was carried out with 40 goats. The 20 goats from each breed were randomly separated to two groups at equal number. Control and experimental groups of the both breeds were milked during feeding as soon as goats return from pasture and after 1 hour-waiting following feeding, respectively. The milk samples taken with interval 30 days from May to October were used for organic acid analysis at a reverse phase high performance liquid chromatography. During lactation hippuric acid was the most abundant organic acid, followed by orotic and uric acids. Experimental group of Kilis goats had the highest level of hippuric acid. Orotic acid was higher in Shami goats than that in Kilis breed. Uric acid was the highest in control group of Shami breed. The 1 hour-waiting period before milking resulted in a significant decrease in uric acid. In general, orotic and uric acid decreased towards the end of lactation whereas hippuric acid markedly increased in the last 3 months of lactation. It was concluded that the 1 hour-waiting before milking after returning from pasture may be especially suggested to Shami goat raisers due to the low uric acid content of the milk. [ABSTRACT FROM AUTHOR]

Saturated vapor pressure, ln( p / Pa ) = (−21316 ± 511)/( T /K)+(41.64 ± 0.11), and enthalpy of sublimation of orotic acid, Δ sub H m 0 ( T m )  = 177 ± 4 kJ/mol, were determined by means of Knudsen effusion mass spectrometry in the temperature range of 423÷493 K. The computational approaches supported the experimental results reported. The theoretical estimation of the gas-phase enthalpy of formation for orotic acid was done with different working reactions used. [ABSTRACT FROM AUTHOR]

Hydrothermal self-assembly of orotic acid (C 5 H 4 N 2 O 4 OrH 3 ) with metal salt Cu(Ac) 2 ·H 2 O yielded a new OrH based hydrogen bonded coordination network of formula [Cu(OrH)(2NH 3 )(H 2 O)]·H 2 O ( 1 ) and [Cu(OrH) (2NH 3 )] 2 ( 2 ). Single crystal X–ray study on 1 confirms that +2 charges on the metal ions (Cu 2+ ) are balanced by OrH anion. N–H⋯O and O–H⋯O hydrogen bonding synthons are the only artifact for the resulting hydrogen bonded copper-OrH architecture. Temperature dependent measurements of magnetic susceptibility reveals the occurrence of competitive exchange interactions with a net ferromagnetic character in 1 ( J  = +0.48 cm −1 ) and strong antiferromagnetic interaction in 2 ( J  = −4.93 cm −1 ). Magnetic superexchange interaction transmitted through equatorial–axial hydrogen bridge system promotes weak ferromagnetic interactions in 1 while in 2 it is in basal-basal position, in which two d x2-y2 orbitals is involved in exchange mechanism reveals the coexistence of two antiferromagnetic exchange pathways, intramolecular much stronger than intermolecular. The natural bond orbital (NBO) analysis applied separately to α and β spin density matrices clearly shows two important magnetic superexchange pathway with shorter Cu⋯Cu contact 5.542(4) Å and 4.845(4) Å or 5.755(1) Å in ( 1 ) and inter dimer 6.665(1) Å and 4.6744(9) Å for ( 2 ). [ABSTRACT FROM AUTHOR]

Milk is the first food consumed by mammals. Its consumption is extremely important because of the nutritional value of milk and its ingredients which support the immune system of newborn babies. Some of the bioactive molecules pass into milk from the mother's blood and some are synthesized in the mammary gland. Sheep milk offers exceptional health benefits; it owes its properties to the rich chemical composition. This high health value of sheep's milk results from the presence of, inter alia, anti-oxidant substances such as CLA. Conjugated linoleic acid (CLA) is one of the most important anti-oxidants of milk fat, and exhibits anti- -carcinogenic and anti-mutagenic effects. Hormones and their precursors are also present in milk, such as leptin. In sheep, the level of leptin is related to body fat content, food intake and the photoperiod length. The period of sexual activity of sheep depends on changes in the length of the day. Lactation is an essential part of the sheep's reproductive cycle. Correct functioning of the endocrine system is essential during lactation. And since proper rearing of offspring depends on the correct course of lactopoiesis, smooth interaction of all the processes is particularly important. [ABSTRACT FROM AUTHOR]

New supramolecular synthon induced complex [Zn(Hor)(Hiso)·3H2O]·H2O (1) is obtained in a selfassembly reaction of zinc nitrate with orotic (H3Or, 1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic) acid and isonicotinamide. The isonicotinamide molecule is hydrolyzed in-situ into isonicotinic (Hiso, pyridine-4-carboxylic) acid. A detailed structural analysis and the role of hydrogen bonding synthons in deciding the overall structural diversity is discussed. The {…H-N-C=O…}2 and {…H-O-C=O…}2 dimers play an important role in the metal-organic architecture of 1. Complex 1 is insoluble in almost all organic solvents as well as in water. The complete decomposition of the compound is achieved above 445°C. [ABSTRACT FROM AUTHOR]

Assembly of orotic acid (H3Or, 1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic) and Cd(NO3)·6H2O yielded a coordination polymer, [(Cd(Hor)·2.5H2O)2]n (1), which has been characterized by X-ray single-crystal diffraction, TGA, and fluorescence spectra. Single-crystal X-ray structural analyses reveal that 1 is a hydrogen-bonded binuclear Cd-orotate coordination polymer in which both Cd2+ ions have different coordination environments with identical distorted octahedral geometry. Crystal data for 1: monoclinic, space group P21/n, a = 7.0209(10) Å, b = 13.974(2) Å, c = 17.541(3) Å, β = 98.842(2)°, V = 1700.5(4) Å, Z = 4, R1 = 0.0269, wR2 = 0.0612, θmax = 25.960. The emission spectrum of the Cd-complex recorded with 265 nm excitation wavelength reveals the complex has strong blue luminescence with the peak maximum 420 nm (2.95 eV) as a result of the n–π* and π–π* transitions on the H3Or ligand. [ABSTRACT FROM AUTHOR]

• Polyacrylamide modified silica stationary phases were prepared through surface-initiated free radical polymerization. • The polymer structure that formed on the silica surface was controllable by regulating the concentrations of VTMS and AM. • The prepared stationary phase exhibited typical HILIC behavior with a lower column back pressure. • The number of theoretical plates and resolution reached 119,966/m and 4.23 for orotic acid, respectively. Polymer modified silica materials are widely used as stationary phases in hydrophilic interaction liquid chromatography (HILIC), whereas a stationary phase with excellent performance is highly desired. In this study, vinyl modified silica was first synthesized through a silane coupling reaction, and then a polyacrylamide modified silica (PAM-SIL) stationary phase was successfully prepared using acrylamide as a copolymer monomer via free radical polymerization. The retention behaviors of polar analytes on the stationary phase under various chromatographic conditions, including acetonitrile content, buffer concentration and pH values were investigated, and a typical hydrophilic interaction retention mechanism was inferred. Exceptionally, the separation performance of the stationary phases could be regulated by controlling the polymer structure. Model analytes separated rapidly on the stationary phase which has an optimal grafting amount of vinyl, with the highest number of theoretical plates of orotic acid reaching 119,966/m. While the stationary phases with high acrylamide concentrations exhibited enhanced retention behavior and higher resolution for analytes. The adjustable separation performance will have huge potential in future separation and analysis applications. [ABSTRACT FROM AUTHOR]