Disease relevance of OXYTHIAMINE

• Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour [1].
• In addition to EMS-like neurological signs, OXY caused dose-dependent increases in hydrocephalus, developmental arrest, and vitelline congestion in the Lake Ontario stock [2].

Psychiatry related information on OXYTHIAMINE

• This series of studies revealed that a 2.5-mg dose of oxythiamine administered over 2 days yielded memory deficits from 10 min following passive avoidance learning [3].

High impact information on OXYTHIAMINE

• Five days of treatment with the TK inhibitor oxythiamine (OT) and the G6PD inhibitor dehydroepiandrosterone-sulfate (0.5 microM each) exerted a 39 and a 23% maximum inhibitory effect on cell proliferation in culture, which was increased to 60% when the two drugs were administered in combination [4].
• The severe inhibition of formate generation by oxythiamin treatment of intact fibroblasts indicates that cleavage through the thiamine pyrophosphate-dependent 2-hydroxyphytanoyl-CoA lyase is the main pathway for the degradation of 2-hydroxyfatty acids [5].
• Experimentally, a dramatic decrease in tumor cell proliferation after the administration of the TK inhibitor oxythiamine (OT) was observed in several in vitro and in vivo tumor models [6].
• The mutant shows markedly reduced activity of thiamine pyrophosphokinase (EC 2.7.6.2) and high resistance to oxythiamine, a thiamine antagonist whose potency depends on thiamine pyrophosphokinase activity [7].
• Administration of oxythiamin resulted in decreases in TKA in both liver and leukocytes [8].

Biological context of OXYTHIAMINE

• Oxythiamine is an antivitamin derivative of thiamine that after phosphorylation to oxythiamine pyro phosphate can bind to the active centres of thiamine-dependent enzymes [9].
• Oxythiamine produced strong apoptosis in in-vitro hosted tumor cells [10].
• Oxythiamine reversed the growth inhibition of Saccharomyces cerevisiae caused by pyrithiamine, although oxythiamine alone inhibited yeast cell growth [11].
• A dominant mutation, responsible for the resistance to oxythiamin in Saccharomyces cerevisiae was mapped on the right arm of chromosome IV, 4.6 cM centromere-distally to trp1 [12].

Anatomical context of OXYTHIAMINE

• Furthermore, hepatocytes were made thiamin deficient with oxythiamin (3mM) as measured by the decreased hepatocyte TK activity [13].

Associations of OXYTHIAMINE with other chemical compounds

• The substrate-induced increases in apical Na permeability were fully reversed by appropriate metabolic inhibitors, i.e. 2-deoxyglucose and oxythiamine [14].
• Brain lipid composition was studied in thiamine deficient rats treated with thiamine antimetabolites (oxythiamine: OT, and pyrithiamine: PT) and thiamine deficient diet (TDD) [15].
• The oxythiamine effects seem to be due to its being phosphorylated to yield diphosphate ester which, as kinetic studies on highly purified PDC from bovine adrenals have shown, is a strong competitive inhibitor (Ki = 0.07 microM) with respect to TPP (Km = 0.11 microM) [16].
• The competitive inhibition of transketolase by oxythiamine and neopyrithiamine was measured and the Ki values obtained of 1.4 and 4.3 mM, respectively, were compared with the affinity of adsorbents prepared from these two inhibitors [17].

Gene context of OXYTHIAMINE

• When the activities were measured in the absence of exogenous thiamine pyrophosphate (TPP), the PDC inhibition was significant after 20 oxythiamine injections [16].
• We hypothesize that somatostatin- and oxythiamine-induced antiproliferative action is mediated by the inhibition of G6PD, transketolase, or both [10].

References