The vitamins
Geoffrey P. Webb in Nutrition, 2019
Thiamin is the precursor of the important coenzyme TPP. TPP is formed by the addition of pyrophosphate (two phosphate groups) at the position marked by an asterisk in Figure 15.6. TPP is an essential coenzyme in several key reactions in metabolism including the following. The conversion of pyruvate to acetyl CoA in carbohydrate metabolism. The conversion of α-ketoglutarate to succinyl CoA in the Krebs cycle. The reactions catalysed by transketolase in the pentose phosphate pathway.
Nutritional Deficiencies
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Thiamine is a cofactor for: Transketolase: This enzyme links glycolysis to the hexose monophosphate shunt (Figure 17.1). The hexose monophosphate shunt is required for the synthesis of: Pentoses (such as ribose phosphate): necessary for the synthesis of nucleotides.Nicotinamide adenine dinucleotide phosphate (NADP): necessary for the synthesis of fatty acids, steroids, and antioxidants.Pyruvate dehydrogenase E1: Pyruvate dehydrogenase is a complex formed by three enzymes (E1, E2, and E3). This complex links the glycolytic pathway with the Krebs cycle. E1 requires thiamine pyrophosphate as a cofactor.Alpha-ketoglutarate dehydrogenase: This enzyme participates in the Krebs' cycle and is involved in the conversion of alpha-ketoglutarate to succinyl-CoA. The deficiencies of this enzyme and E1 lead to decreased adenosine triphosphate (ATP) production and cellular dysfunction.
Vitamin Deficiency in Patients with Terminal Cancer
Victor R. Preedy in Handbook of Nutrition and Diet in Palliative Care, 2019
Low plasma thiamine levels are common and are associated with increased mortality in patients in intensive care units (Donnino et al. 2010). Thiamine deficiency is also well described in patients with advanced cancer (Barbato and Rodriguez 1994). In particular, thiamine deficiency presents in patients with rapidly growing malignancies. To support rapid growth and proliferation, tumour cells require large amounts of energy, which in part is derived from the anaerobic breakdown of glucose to ATP. The pentose phosphate pathway is important in glucose metabolism, with transketolase an integral enzyme for the nonoxidative synthesis of 5-carbon sugars. Thiamine is metabolised to thiamine pyrophosphate, the cofactor of transketolase. The upregulation of transketolase activity during tumour progression has been widely reported.
Differences in the efficiency of 3-deazathiamine and oxythiamine pyrophosphates as inhibitors of pyruvate dehydrogenase complex and growth of HeLa cells in vitro
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Ewa Grabowska, Magdalena Czerniecka, Urszula Czyżewska, Aneta Zambrzycka, Zenon Łotowski, Adam Tylicki
The impact of OT on eukaryotic cells was studied on mammals (in vitro and in vivo) as well as on yeast. Analysis of the amount of cells of S. cerevisiae cells showed that OT reduced the total amount of cells6. Research done on mice showed the impact of the OT on the Ehrlich’s tumour35, and this observation was similar to the findings of our research. Data on the impact on fibroblasts showed no differences between the viability of cells with increasing concentrations of OT after 24 and 48 h36. Our research was maintained for approximately 4 days, what may play a role in the viability of cells. These suggest that fibroblasts are less sensitive than HeLa cells to OT treatment. Research done on MIA PaCa-2 cells in in vitro conditions showed that after exposure of cells to OT, their RNA content was reduced by about 45%, as well as the total amount of DNA (decreased by 20%)37. Moreover, in the same study, cell proliferation was inhibited by 31 and 41% at OT concentrations of 10−8 × 5 µM and 10−7 × 5 µM OT, respectively37. Moreover, proteomic studies on MIA PaCa-2 cells after exposure to OT showed that the amount of transketolase in cells was lower compared to the control group38. In addition, their data38 showed that the inhibition of transketolase by OT may have a wider impact on the cancer cells (such as activation of the apoptosis pathway). Our experiment done on HeLa cells confirmed the inhibitory properties of OT as well as OTPP.
Targeting endothelial cell metabolism in cancerous microenvironment: a new approach for anti-angiogenic therapy
Published in Drug Metabolism Reviews, 2022
Parisa Mohammadi, Reza Yarani, Azam Rahimpour, Fatemeh Ranjbarnejad, Joana Mendes Lopes de Melo, Kamran Mansouri
The PPP is a shunt on the glycolysis pathway that produces ribose-5-phosphate and NADPH required for cell proliferation. The first is required for DNA replication and the second is used for NO production, regeneration of reduced glutathione, and FA biosynthesis (Li et al. 2019). Although deletion or weakening of this shunt has a devastating effect on angiogenesis, either through inhibition of transketolase or G6PD, it can also affect physiological angiogenesis. Zhaoyu Qin et al. have demonstrated that transketolase can promote the viability of hepatocellular carcinoma cells in a non-metabolic manner via its nuclear localization and epidermal growth factor receptor (EGFR) pathway in addition to its metabolic role (Qin et al. 2019). Since the recent report on the non-metabolic role of this enzyme in cancer cell development, further investigation on TEC requires to be done. Preventing its entry into the nucleus or blocking the EGFR pathway may specifically inhibit pathological angiogenesis.
Recurrent Wernicke’s encephalopathy in pregnancy: A case report
Published in Nutritional Neuroscience, 2019
Angela Stephens, Khilen Patel, Ashwin Rao, Paul Browne, Susanna Raley, Linda Street
Diagnosis requires the clinical syndrome (AMS, ophthalmalgia, and gait disturbance), depleted thiamine levels, and abnormal brain imaging. Serum thiamine concentrations or measurements of erythrocyte transketolase activity are low. MRI has a sensitivity and specificity of 53 and 93%, respectively, for diagnosing WE.2 Image findings include bilateral, symmetric increased T2 signals in the paraventricular regions of the thalamus, hypothalamus, mammillary bodies, periaqueductal region, the floor of the fourth ventricle, and the cerebellum.2 These regions are sensitive to thiamine levels due to cellular dependence on oxidative metabolism.3 Image findings are present 2–3 weeks following thiamine depletion.9
Related Knowledge Centers
- Calvin Cycle
- Enzyme
- Pentose Phosphate Pathway
- Photosynthesis
- Thiamine Pyrophosphate
- Gene
- Xylulose 5-Phosphate
- Ribose 5-Phosphate
- Sedoheptulose 7-Phosphate
- Glyceraldehyde 3-Phosphate