Disease relevance of Aneurin

• Treatment with pharmacologic doses of thiamine ameliorates the megaloblastic anaemia and diabetes mellitus [1].
• High thiamine levels in sudden infant-death syndrome [2].
• We report here that mRNAs encoding enzymes involved in thiamine (vitamin B(1)) biosynthesis in Escherichia coli can bind thiamine or its pyrophosphate derivative without the need for protein cofactors [3].
• Ethanol-induced intoxication and hypothermia were studied in rats approximately 7 months after severe thiamine deficiency, when treated rats appeared to have recovered their physical health [4].
• Search terms included poisoning, overdose, toxicity, naloxone, glucose, thiamine, and flumazenil [5].

Psychiatry related information on Aneurin

• The Wernicke-Korsakoff syndrome is a thiamine-deficiency disorder occurring primarily among alcoholics [6].
• Thiamine deficiency, Wernicke's encephalopathy, and AIDS [7].
• Brain thiamine, its phosphate esters, and its metabolizing enzymes in Alzheimer's disease [8].
• Intermittent thiamine deficiency in the rhesus monkey. II. Evidence for memory loss [9].
• As a consequence of individual differences in susceptibility to thiamine deficiency, neurological symptoms and signs were more related to the profile of neural damage than to the number or duration of deprivation episodes [10].

High impact information on Aneurin

• In Bacillus spp, genes responsible for thiamin and riboflavin biosynthesis are organized in tightly controllable operons [11].
• Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome [1].
• A defect in the plasma membrane transport of thiamine has been demonstrated in erythrocytes and cultured skin fibroblasts from TRMA patients [1].
• We have previously demonstrated that fibroblasts from people with TRMA lack high-affinity thiamine transport [12].
• Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270) [13].

Chemical compound and disease context of Aneurin

• A complementation study of Escherichia coli thiF(-) using thiF(C184S) suggests that this conjugate is an essential intermediate involved in the biosynthesis of the thiazole moiety of thiamin [14].
• Pyrithiamine is an inhibitor of thiamine metabolism that induces neurological symptoms similar to that of Wernicke-Korsakoff Syndrome in animals [15].
• Moderate to severe protein and calorie deficiencies, as well as thiamine and vitamin C deficiencies, inhibited the host's granulomatous response to S mansoni eggs, which is a form of delayed-type hypersensitivity [16].
• Escherichia coli pyruvate oxidase, a peripheral membrane homotetrameric flavoprotein, exposes its C-terminal lipid binding site in the presence of substrate pyruvate and co-factor thiamine pyrophosphate Mg2+ and binds tightly to phospholipid bilayers during catalysis [17].
• Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine [18].

Biological context of Aneurin

• Expression of a gene encoding a known yeast thiamine transporter, THI10 (refs 8-10), in TRMA mutant cells prevents apoptotic cell death in thiamine-depleted medium [12].
• Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression [3].
• The association of the thiamine-responsive phenotype with a subset of the type II MSUD patients studied is also discussed [19].
• Cultured diploid fibroblasts were grown in thiamine-free medium and dialyzed serum [20].
• When unidirectional flux across the jejunum was measured, saturation kinetics was again demonstrated for low thiamine concentrations [21].

Anatomical context of Aneurin

• We studied a thiamine-requiring enzyme in cultured cells from four patients with the Wernicke-Korsakoff syndrome to determine whether these patients have a genetic predilection to thiamine deficiency [22].
• Thiamine transport by basolateral rat liver plasma membrane vesicles [23].
• INTERPRETATION: In adults admitted to hospital in Thailand, thiamine deficiency commonly complicates acute falciparum malaria, particularly in severe infections, and could contribute to dysfunction of the central nervous system [24].
• In vivo studies with [35-S]-thiamine hydrochloride revealed, in all segments of small intestine, saturation kinetics for low thiamine concentrations (0.06 to 1.5 muM), but a linear relationship between high concentrations (2 to 560 muM) and absorption [21].
• These intracellular capsid-binding membranes (ICBMs) were not stained by cytochemical markers for endoplasmic reticulum (ER) (glucose-6-phosphatase) or trans Golgi cisternae (thiamine pyrophosphatase, acid phosphatase) but were labeled by Ricinus communis agglutinin I (RCA) in thin, frozen sections [25].

Associations of Aneurin with other chemical compounds

• The apparent Km for thiamine pyrophosphate was 195 +/- 31 micron for transketolase in extracts of the patients' cells as compared to 16 +/- 2 micron in six control lines (means +/- S.E.M.: P less than 0.001) [22].
• The abnormality in transketolase persisted through serial passages in tissue culture in cells grown in medium containing excess thiamine and no ethanol, indicating that the aberrations were genetic rather than dietary [22].
• The cost of adequately fortifying alcoholic beverages is estimated to range from $3 million per year if allithiamines are used, to as much as $17 million per year if thiamine hydrochloride proves necessary [6].
• Structure of the thiamine- and flavin-dependent enzyme pyruvate oxidase [26].
• Significant progress has been made in recent years toward understanding the mechanisms and regulation of intestinal absorption of water-soluble vitamins from the diet, especially those that are transported by a specialized carrier-mediated mechanism (i.e., ascorbic acid, biotin, folate, riboflavin, thiamin, and pyridoxine) [27].

Gene context of Aneurin

• In this segment, each family displayed one of two different missense mutations that altered the coding sequence of SLC19A3, the gene for a transporter related to the reduced-folate (encoded by SLC19A1) and thiamin (encoded by SLC19A2) transporters [28].
• Bone marrows from thiamin-deficient Slc19a2(-/-) mice were abnormal, with a megaloblastosis affecting the erythroid, myeloid and megakaryocyte lines [29].
• Northern blot analysis demonstrated that THI10 gene expression is regulated at the mRNA level by intracellular thiamin pyrophosphate and that it requires a positive regulatory factor encoded by THI3 gene [30].
• Isolation and characterization of a thiamin pyrophosphokinase gene, THI80, from Saccharomyces cerevisiae [31].
• Northern blot analysis demonstrated that THI6 gene expression is regulated at the mRNA level by intracellular thiamin pyrophosphate, a coenzyme form of thiamin, and that it requires the positive regulatory factors encoded by the THI2 and THI3 genes [32].

Analytical, diagnostic and therapeutic context of Aneurin

• To test efficacy in vivo, we added 1% thiamine to the drinking water of Long Evans Cinnamon rats, an animal model of Wilson's disease [33].
• The Mg(II) binding residue Asp-260, which is located within the thiamine pyrophosphate binding motif of the alpha-ketodecarboxylase family, was shown by site-directed mutagenesis to play an important role in catalysis [34].
• This review is limited to progress in the development of new or improved laboratory procedures to assess the nutriture of thiamin, riboflavin, niacin, vitamin B6, and folic acid [35].
• We found in a DNA microarray analysis that the expression of THI genes increased 10- to 90-fold in response to thiamin deprivation, and likewise, the expression of THI2 and THI3 increased 17-fold and threefold, respectively [36].
• A control group of animals fed no alcohol and maintained on a thiamin-replete diet was used for comparison [37].

References