2-Oxo acids derived from amino acids, glucose, and fatty acids are key intermediates in energy production. During diabetes, energy production is known to be lower than in healthy individuals. However, it was unknown whether the production of 2-oxo acids is impacted by diabetes. In the present study, I compared the quantities of 2-oxo acids (pyruvic acid, oxaloacetic acid, 2-oxoglutaric acid, 2-oxoadipic acid, 2-oxoisovaleric acid, 2-oxo-3-methylvaleric acid, and 2-oxo-4-methylvaleric acid) excreted in the urine of normoglycemic control rats and rats with streptozotocin-induced diabetes, which reflect the quantities of unused 2-oxo acids in the body. Greater urinary excretion of unused 2-oxo acids thus implies an impairment in energy production. The respective quantities of urinary pyruvic acid + oxaloacetic acid (measured together), 2-oxoglutaric acid, 2-oxoadipic acid, 2-oxoisovaleric acid, 2-oxo-3-methylvaleric acid, and 2-oxo-4-methylvaleric acid in the diabetic rats were 2.0- (p<0.0001), 2.5- (p<0.0001), 1.5- (p=0.008), 7.6- (p<0.0001), 6.1- (p<0.0001), and 2.1-fold (p<0.0001) greater than in the control rats per 1 g food intake. Thus, the biggest differences were observed in 2-oxoisovaleric acid (a catabolite of valine) and 2-oxo-3-methylvaleric acid (a catabolite of isoleucine). These findings indicate that energy production in the body is suppressed under diabetic conditions.
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http://dx.doi.org/10.3177/jnsv.64.292 | DOI Listing |
Pharmaceuticals (Basel)
October 2024
Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, Ukraine.
Designing novel biologically active compounds with anti-inflammatory properties based on condensed quinazolines is a significant area of interest in modern medicinal chemistry. In the present study, we describe the development of promising new bioactive molecules through the bioisosteric replacement of a carbon atom with a sulfur atom in anti-inflammatory agents, specifically 3-methyl-2-oxo-2-[1,2,4]triazino[2,3-]quinazolin-6-yl)butanoate. Design and synthetic studies have led to the series of previously unknown substituted 2-[((3-R-2-oxo-2-[1,2,4]triazino[2,3-]quinazolin-6-yl)methyl)thio]carboxylic acids and their esters.
View Article and Find Full Text PDFJ Org Chem
December 2024
Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
In the Au(PPh)Cl/AgOTf/TsOH/MeCN/N/25 °C system, diastereoselective synthesis of -3a,8a-dihydrofuro[2,3-]benzofuran derivatives with a substituent at the 8a-position has been achieved by using 1-(2-hydroxyphenyl)-3-arylprop-2-yn-1-ols and β-oxoketones (amides, acid) as starting materials. The studies revealed that the acidity of methylene in substrates plays a key role in the differential reactions. A stronger acidity of the methylene is favorable in the desired conversion.
View Article and Find Full Text PDFBiochemistry (Mosc)
October 2024
Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
The risk of developing diabetes and cardiometabolic disorders is associated with increased levels of alpha-aminoadipic acid and disturbances in the metabolism of branched-chain amino acids. The side effects of the widely used antidiabetic drug metformin include impaired degradation of branched-chain amino acids and inhibition of intracellular thiamin transport. These effects may be interconnected, as thiamine deficiency impairs the functioning of thiamine diphosphate (ThDP)-dependent dehydrogenases of 2-oxo acids involved in amino acids degradation, while diabetes is often associated with perturbed thiamine status.
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
October 2024
Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Damaged 2'-deoxyribonucleotides cause mutations, cancer, cell death, and aging. The Orf135 (NudG) protein catalyzes the hydrolysis of various 2'-deoxyribonucleotides including an oxidized form of dATP, 2-oxo-1,2-dihydro-2'-deoxyadenosine 5'-triphosphate (dATP, 2-hydroxy-2'-deoxyadenosine 5'-triphosphate). The best substrate is 5-methyl-2'-deoxycytidine 5'-triphosphate (dCTP), and the protein prefers dCTP over dATP by ∼200-fold in vitro.
View Article and Find Full Text PDFChem Biol Drug Des
October 2024
Al-Balqa Applied University, Salt, Jordan.
The higher prevalence of cancer and the unmet need for antioxidant/anti-inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication.
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