Browsing by Subject "Thiamine"

Now showing 1 - 3 of 3
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    Identification of Charge Transfer Transitions Related to Thiamin-Bound Intermediates on Enzymes Provides a Plethora of Signatures Useful in Mechanistic Studies
    (American Chemical Society, 2014-04-08) Patel, Hetalben; Nemeria, Natalia S.; Andrews, Forest H.; McLeish, Michael J.; Jordan, Frank; Department of Chemistry & Chemical Biology, School of Science
    Identification of enzyme-bound intermediates via their spectroscopic signatures, which then allows direct monitoring of the kinetic fate of these intermediates, poses a continuing challenge. As an electrophilic covalent catalyst, the thiamin diphosphate (ThDP) coenzyme forms a number of noncovalent and covalent intermediates along its reaction pathways, and multiple UV–vis and circular dichroism (CD) bands have been identified at Rutgers pertinent to several among them. These electronic transitions fall into two classes: those for which the conjugated system provides a reasonable guide to the observed λmax and others in which there is no corresponding conjugated system and the observed CD bands are best ascribed to charge transfer (CT) transitions. Herein is reported the reaction of four ThDP enzymes with alternate substrates: (a) acetyl pyruvate, its methyl ester, and fluoropyruvate, these providing the shortest side chains attached at the thiazolium C2 atom and leading to CT bands with λmax values of >390 nm, not pertinent to any on-pathway conjugated systems (estimated λmax values of <330 nm), and (b) (E)-4-(4-chlorophenyl)-2-oxo-3-butenoic acid displaying both a conjugated enamine (430 nm) and a CT transition (480 nm). We suggest that the CT transitions result from an interaction of the π bond on the ThDP C2 side chain as a donor, and the positively charged thiazolium ring as an acceptor, and correspond to covalent ThDP-bound intermediates. Time resolution of these bands allows the rate constants for individual steps to be determined. These CD methods can be applied to the entire ThDP superfamily of enzymes and should find applications with other enzymes.
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    Thiamine Deficiency Leading to Refractory Lactic Acidosis in a Pediatric Patient
    (hindawi publishing corporation, 2017) Teagarden, Alicia M.; Leland, Brian D.; Rowan, Courtney M.; Lutfi, Riad; Pediatrics, School of Medicine
    Thiamine plays a critical role in energy metabolism. Critically ill children and adults may develop thiamine deficiency with ultimately increased mortality due to potentially irreversible consequences of severe type B lactic acidosis. We report a case of an unvaccinated term neonate with malignant pertussis requiring extracorporeal membrane oxygenation and continuous renal replacement therapy, who developed profound lactic acidosis of unknown etiology. After countless evaluations for likely causes, the patient was ultimately determined to have thiamine deficiency and her acidosis resolved rapidly with vitamin supplementation.
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    Wernicke’s encephalopathy in adolescents with anorexia nervosa
    (Elsevier, 2023) Safran, Jeremy T.; Bodaghi, Mahdieh; Sherwin, Nomi K.; Wallace, Jessica R.; Pediatrics, School of Medicine
    Anorexia Nervosa (AN) has always been prevalent in adolescents. During the COVID-19 pandemic, the eating disorder community across the world has noted a sharp increase in adolescent patients with AN and the severity of medical compromise. Rarely seen sequelae have become increasingly more common. This case report describes two previously healthy female adolescents with severe malnutrition due to AN admitted for nutritional stabilization who exhibited paranoid delusions responsive to thiamine and olanzapine. Though neither exhibit the full triad or all the Caine criteria for Wernicke's Encephalopathy (WE), the triad will not present completely in most patients with WE, especially in the pediatric population. Having one symptom of the triad is indicative of WE. Due to the decreased number of clinical criteria for Wernicke's encephalopathy coupled with the lack of typical brain MRI findings found in these patients, we recommend a high index of suspicion for WE and investigation with thiamine. Thiamine supplementation should be standard care in AN with oral supplementation in stable conditions. In the case of refeeding syndromes, preventative parenteral thiamine 100 mg IV qd, and in the case of thiamine deficiency, thiamine 500 mg IV TID.