China
Africa
Explore chapters and articles related to this topic
Cooperation of Vagal and Central Neural Systems in Monitoring Metabolic Events Controlling Feeding Behavior
Published in Sue Ritter, Robert C. Ritter, Charles D. Barnes, Neuroanatomy and Physiology of Abdominal Vagal Afferents, 2020
S. Ritter, N.Y. Calingasan, B. Hutton, T.T. Dinh
Additional work by these investigators suggested that the hypophagic effect of subcutaneous injections of the above metabolites was related to the generation of reducing equivalents by their mitochondrial oxidation. Glycerol, L- malate and L-lactate were compared to their immediate oxidation products (dihydroxyacetone, oxaloacetate and pyruvate, respectively) for their hypophagic potency. Glycerol and L-malate suppressed feeding, whereas their oxidation products did not. Both lactate and pyruvate suppressed feeding, suggesting that the oxidative decarboxylation of pyruvate, which requires the enzyme pyruvate dehydrogenase, may be crucial for the hypophagic effect of both lactate and pyruvate. This hypothesis is supported by their finding that neither lactate nor pyruvate suppresses feeding in rats maintained on high dietary fat. High dietary fat is known to decrease pyruvate dehydrogenase activity and thus inhibit pyruvate oxidation in favor of the gluconeogenic pathway.
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The disease is associated with a failure of oxidative decarboxylation of branched chain amino acids. Three keto acids −α-ketoisovaleric, β-ketoisocaproic and α-keto-β-methylvaleric acids—metabolites of valine, leucine and isoleucine, respectively, are accumulated in the serum and cerebrospinal fluid and excreted in the urine in great amounts. These keto acids are also present in tissues in large concentrations, and secondarily, the plasma levels of valine, leucine, and isoleucine are also increased. Alloisoleucine is also present in serum, formed probably by transamination from α-keto-β-methylvaleric acid. The impaired decarboxylation brings about an increased production of α-ketobutyric acid responsible for the odor. The enzyme systems responsible for the oxidative decarboxylation of a-keto acids arefound in hepatic mitochondria and leukocytes. The reaction requires coenzyme A as a cofactor. Patients with maple syrup disease cannot combine keto acids with coenzyme A during oxidative decarboxylation and in some cases, conversion of the coenzyme A complex is blocked.
Modulation of Lipid Biosynthesis by Stress in Diatoms
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Bing Huang, Virginie Mimouni, Annick Morant-Manceau, Justine Marchand, Lionel Ulmann, Benoit Schoefs
In microalgae, there is only fragmented information about carbon flux toward the generation of acetyl-CoA for FA synthesis and in particular about the regulation of the different acetyl-CoA-generating routes (Shtaida, Khozin-Goldberg and Boussiba, 2015). The study of Ma et al. (2014) has shed some new light on the regulatory mechanisms of PDC. PDC catalyzes the irreversible oxidative decarboxylation of pyruvate to acetyl-CoA. The activity of the mitochondrial PDC, unlike its plastid counterpart, is repressed by pyruvate dehydrogenase kinase (PDK). The silencing of the mitochondrial PDK-encoding gene (PtPDK) resulted in an increase of up to 82% of the neutral lipid content, revealing an important contribution of the mitochondrial acetyl-CoA pool to the lipid metabolism in diatoms (Ma et al., 2014).
Investigation of the pharmacokinetics and metabolic fate of Fasiglifam (TAK-875) in male and female rats following oral and intravenous administration
Published in Xenobiotica, 2023
Billy J. Molloy, Adam King, Lee A. Gethings, Robert S. Plumb, Russell J. Mortishire-Smith, Ian D. Wilson
This study has established that the pharmacokinetics of fasiglifam in male and female rats was similar but that there was a clear sex difference in the urinary excretion of fasiglifam. However, in line with previously published data (Kogame et al. 2019a) urine was a minor route of excretion. Thus up to10-fold higher drug concentrations were detected in urine samples obtained from females compared to males administered the same dose. The investigation of the plasma for biotransformation products of fasiglifam using UHPLC/cIM/MS identified a number of novel metabolites of the drug. Several of these previously undescribed metabolites, indicative of a novel route of oxidative decarboxylation for the drug, provide evidence for a third pathway for the production of reactive metabolites (in addition to the production of acylCoA- and acylglucuronide conjugates) with potential implications for toxicity. However, in the absence of a more in-depth quantitative of the exposure of the rat to this additional reactive metabolite-producing pathway it is difficult to estimate its importance, if any, to the well-established DILI resulting from the administration of fasiglifam.
Targeting epigenetic regulators in the treatment of T-cell lymphoma
Published in Expert Review of Hematology, 2020
IDHs catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate. IDH has three isoforms: IDH1, IDH2, and IDH3. Mutations in IDH1 or IDH2 lead to the accumulation of 2-hydroxyglutarate (2-HG), which inhibits several demethylation pathways, including those driven by ten-eleven translocation (TET) proteins, and therefore act as indirect epigenetic regulators [10]. Dysregulation of the IDH epigenetic pathway has been well studied in T-cell lymphoma. Whole-exome sequencing has revealed recurrent IDH2 mutations in a variety of PTCL subtypes, including around 30% of AITLs [40,120,121]. The R172 residue is most commonly affected by IDH2 mutations, and is associated with the highest resultant levels of 2-HG compared with hotspot mutations affecting IDH1R132 and IDH2R140 [122]. Mutations may prove to be a key biomarker to select patients to receive IDH inhibitors regardless of tumor pathology. Notably, T-cell lymphomas having IDH2 mutations express programmed cell death protein-1 (PD-1) and are associated with downregulation of TH1 differentiation genes such as STAT1 and IFNG [40,120,121]. Integrative analysis has suggested a possible role of IDH gene mutations in lymphomagenesis, demonstrating increased methylation of the promoters that regulate T-cell receptor signaling and T-cell differentiation in cell lines with IDH2R172K [40].
The Dichotomous Effect of Thiamine Supplementation on Tumorigenesis: A Systematic Review
Published in Nutrition and Cancer, 2022
José Reginaldo Alves de Queiroz Júnior, Jarson Pedro da Costa Pereira, Leonardo Lucas Pires, Carina Scanoni Maia
Thiamin (vitamin B1) in particular is a cofactor of two important metabolic pathways. When combined with phosphorus, the coenzyme thiamin pyrophosphate (TPP) is formed. It is essential for oxidative decarboxylation of pyruvate, forming acetate and acetyl coenzyme A, the main component of the tricarboxylic acid cycle. In addition, thiamin also participates in the pathway catalyzed by transketolase, the main enzyme in the pentose pathway (the most important producer of NADPH and ribose) (8). In order to relate the co-enzymatic functions of vitamin B1 with the energetic enzymatic mechanism of the tumor cell, some authors have raised the hypothesis of the relationship between serum thiamin levels and tumor proliferation (7, 9, 10).