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Mitochondrial Function in Diabetes: Pathophysiology and Nutritional Therapeutics
Published in Jeffrey I. Mechanick, Elise M. Brett, Nutritional Strategies for the Diabetic & Prediabetic Patient, 2006
In “thiamin-responsive megaloblastic anemia” (TRMA), the saturable component of the thiamin transporter (THTR1) is absent [254]. This component is similar to the reduced-folate transporter and is encoded by a member of the solute carrier gene superfamily, the SLC19A2 gene, in chromosome 1q23.3 [255,256]. Several different mutations in the SLC19A2 gene have been associated with TRMA [257]. TRMA is similar to “Rogers syndrome,” which is associated with DM and sensorineural deafness, and responds to pharmacologic doses of thiamin [258–260].
Laboratory testing for mitochondrial diseases: biomarkers for diagnosis and follow-up
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Abraham J. Paredes-Fuentes, Clara Oliva, Roser Urreizti, Delia Yubero, Rafael Artuch
The active form of thiamine is thiamine diphosphate, which participates in mitochondrial metabolism as the cofactor of three mitochondrial dehydrogenases: pyruvate, ketoglutarate, and branched-chain keto acid dehydrogenases. Thiamine is phosphorylated by one specific kinase (e.g. TPK1) and is incorporated into the mitochondria by different mitochondrial thiamine carriers (e.g. those coded by SLC19A2, SLC19A3, and SLC25A19 genes). Mutations in these genes are associated with different phenotypes that lead to impaired mitochondrial metabolism. The most consistent biomarkers are the decrease in free thiamine concentrations in CSF and fibroblasts in SLC19A3 transport deficiency, and low whole blood thiamine diphosphate values in TPK1 deficiency (Table 1) [60,61]. Although it is not always observed, thiamine deficiency usually leads to increases in other surrogate biomarkers as a consequence of thiamine-dependent enzymes: lactate (caused by PDH deficiency), alpha-ketoglutarate (caused by alpha-ketoglutarate dehydrogenase deficiency), and branched-chain keto acids (caused by branched-chain keto acid dehydrogenase deficiency) (Table 1) [62].
Thiamine and phosphate esters concentrations in whole blood and serum of patients with alcohol use disorder: a relation with cognitive deficits
Published in Nutritional Neuroscience, 2021
Laurent Coulbault, Ludivine Ritz, François Vabret, Coralie Lannuzel, Céline Boudehent, Marie Nowoczyn, Hélène Beaunieux, Anne Lise Pitel
Alcohol also directly regulates activity or expression of thiamine pyrophosphokinase in cells, the key enzyme of thiamine phosphorylation in human, and thiamine pyrophosphatase, which dephosphorylates TDP and produces TMP. Chronic alcohol consumption thus affects thiamine phosphorylation and dephosphorylation rate, and deregulates TDP levels and its sequestration in cells [33,34]. Recent studies also demonstrated that expression of thiamine transporters (SLC19A2 and SLC19A3) is reduced after chronic alcohol exposure limiting intestinal thiamine absorption, and thiamine transport across Blood Brain Barrier in rodents [29,35]. These data suggest that the expression of thiamine transporters is reduced in many tissues such as liver, but is also probably reduced in AUD patients in blood brain barrier and brain. A reduced expression of thiamine transporters could affect thiamine transport across the blood–brain barrier, and reduce the availability of thiamine in glucose-dependent and vulnerable brain regions involved in the memory process.
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
SLC19A1 is a transporter responsible for the transfer of thiamine monophosphate across the cell membrane26,29,30. Research done by Mkrtchyan et al.31 showed that N2A cells had about five times higher amount of SLC25A19 mRNA than astrocytes, but at the same time they exhibited similar expression of genes encoding SLC19A231. However, in some other cancer cells, the expression of genes encoding transporters (such as SLC19A3, SLC19A2)26,32–34 is higher than in normal cells. Moreover, some cancer cells show higher expression of genes encoding SLC25A19 transporter26, which may indicate a significant role of this transporter in the availability of thiamine phosphates. All the mentioned data suggest that the specific reaction of HeLa cells in the presence of thiamine derivatives may be related to the expression of genes encoding those transporters as well as the specificity of these transporters.