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Showing papers on "Thiamine published in 1997"


Journal ArticleDOI
03 Jan 1997-Science
TL;DR: The protein component accelerated the deprotonation of the C2 atom by several orders of magnitude, beyond the rate of the overall enzyme reaction, and the earlier proposed concerted mechanism or stabilization of a C2 carbanion can be excluded.
Abstract: The controversial question of how thiamine diphosphate, the biologically active form of vitamin B1, is activated in different enzymes has been addressed. Activation of the coenzyme was studied by measuring thermodynamics and kinetics of deprotonation at the carbon in the 2-position (C2) of thiamine diphosphate in the enzymes pyruvate decarboxylase and transketolase by use of nuclear magnetic resonance spectroscopy, proton/deuterium exchange, coenzyme analogs, and site-specific mutant enzymes. Interaction of a glutamate with the nitrogen in the 1'-position in the pyrimidine ring activated the 4'-amino group to act as an efficient proton acceptor for the C2 proton. The protein component accelerated the deprotonation of the C2 atom by several orders of magnitude, beyond the rate of the overall enzyme reaction. Therefore, the earlier proposed concerted mechanism or stabilization of a C2 carbanion can be excluded.

272 citations


Journal ArticleDOI
TL;DR: The literature concerning Wernicke-Korsakoff syndrome is reviewed and treatment is based on restoration of thiamine, although this is insufficient to prevent the psychological decline of a great number of patients.
Abstract: Alcohol abuse is one of the most serious problems in public health and the Wernicke-Korsakoff syndrome is one of the gravest consequences of alcoholism. The pathology is often undiagnosed in its less evident presentations, therefore an accurate diagnostic approach is a critical step in treatment planning. Treatment is based on restoration of thiamine, although this is insufficient to prevent the psychological decline of a great number of patients. The cognitive impact of the pathology is derived from the interaction of alcoholic neurotoxicity, thiamine deficiency and personal susceptibility. In this article, the literature concerning Wernicke-Korsakoff syndrome is reviewed.

250 citations


Journal ArticleDOI
TL;DR: An improvement in thiamine status was associated with reports of being more clearheaded, composed and energetic, and reaction times were faster following supplementation.
Abstract: One hundred and twenty young adult females took either a placebo or 50 mg thiamine, each day for 2 months. Before and after taking the tablets, mood, memory and reaction times were monitored. An improvement in thiamine status was associated with reports of being more clearheaded, composed and energetic. The taking of thiamine had no influence on memory but reaction times were faster following supplementation. These influences took place in subjects whose thiamine status, according to the traditional criterion, was adequate.

103 citations


Journal ArticleDOI
TL;DR: Thi4 and its plant homolog appear to be dual functional proteins with roles in thiamine biosynthesis and mitochondrial DNA damage tolerance.

101 citations


Journal ArticleDOI
TL;DR: On the basis of a linkage analysis of affected families of Alaskan and of Italian origin, it is found that the TRMA-syndrome gene maps to a region on chromosome 1q23.2-23.3 (maximum LOD score of 3.3) and the putative disease-gene interval has been confirmed and narrowed, suggesting genetic homogeneity.
Abstract: Summary Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment. On the basis of a linkage analysis of affected families of Alaskan and of Italian origin, we found, using homozygosity mapping, that the TRMA-syndrome gene maps to a region on chromosome 1q23.2-23.3 (maximum LOD score of 3.7 for D1S1679). By use of additional consanguineous kindreds of Israeli-Arab origin, the putative disease-gene interval also has been confirmed and narrowed, suggesting genetic homogeneity. Linkage analysis generated the highest combined LOD-score value, 8.1 at a recombination fraction of 0, with marker D1S2799. Haplotype analysis and recombination events narrowed the TRMA locus to a 16-cM region between markers D1S194 and D1S2786. Several heterozygote parents had diabetes mellitus, deafness, or megaloblastic anemia, which raised the possibility that mutations at this locus predispose carriers in general to these manifestations. Characterization of the metabolic defect of TRMA may shed light on the role of thiamine deficiency in such common diseases.

92 citations


Journal ArticleDOI
TL;DR: Findings suggest that increased formation of free radicals occurs during the more acute symptomatic stage of thiamine deficiency and may contribute to the structural damage described in this model of Wernicke’s encephalopathy.
Abstract: Concentration of reactive oxygen species (ROS) and the antioxidant glutathione (GSH) was measured in thalamus and cortex after 13 and 14 days of pyrithiamine-induced thiamine deficiency (PTD) in the rat The concentration of ROS was significantly elevated in thalamus and cortex on day 14 when righting reflexes were absent and spontaneous seizures occured No significant changes in GSH concentration were observed in thalamus or cortex on either day of treatment These findings suggest that increased formation of free radicals occurs during the more acute symptomatic stage of thiamine deficiency and may contribute to the structural damage described in this model of Wernicke's encephalopathy

83 citations


Journal ArticleDOI
01 Jul 1997
TL;DR: A longer germination time led to a recovery of the decrease in the thiamine content that was observed to occur during the initial period of germination, and significant increases of the riboflavin and available niacin contents in lentils, independently of other conditions (light and number of daily rinses), were observed.
Abstract: The effect of germination on the thiamine, riboflavin, as well as the available and total niacin contents in two varieties of lentils (Lens culinaris, var. vulgaris, Lens culinaris, var. variabilis) and faba beans (Vicia faba, L., var. major) were investigated. Germination of the three legumes, carried out for 6 days at 20 °C in the dark and with daily rinsing, led to a significant reduction of the thiamine content and a significant increase of the riboflavin as well as the total and available niacin contents. For Lens culinaris, var. vulgaris the effect of different conditions during the germination procedure (light, time and number of rinses) on water-soluble vitamins was studied. The presence or absence of light had no significant effect on the thiamine and riboflavin contents in germinated lentils, while the niacin content was higher when germination was conducted in the light. The increased number of rinses during the germination process had no significant effect on the thiamine content in lentils, whereas a significant decrease in the riboflavin and available niacin contents was observed, except for riboflavin when germination was carried out for 6 days and for available niacin when germination was carried out for 3 days without light, where no significant changes were detected. A longer germination time led to a recovery of the decrease in the thiamine content that was observed to occur during the initial period of germination, and significant increases of the riboflavin and available niacin contents in lentils, independently of other conditions (light and number of daily rinses), were observed. When germination was carried out for 10 days in the dark and with daily rinsing, maximal increases of the riboflavin and available niacin contents with minimal decreases in the thiamine content were observed.

69 citations


Journal ArticleDOI
TL;DR: In this article, the amount of labeled thiamine taken up by the duodenal mucosa was measured radiometrically, and it was shown that the thiamines uptake by duoderienal mucus had a hyperbolic time course, reaching equilibrium at 10 min.

68 citations


Journal ArticleDOI
TL;DR: It is demonstrated that a single episode of thiamine deficiency can selectively damage cortical white matter tracts while sparing the thalamus and mammillary body and may be a critical factor responsible for the pathological and behavioral changes observed in alcoholics without Wernicke's encephalopathy.
Abstract: The relative etiologic roles of ethanol and thiamine deficiency in the cortical atrophy and loss of cerebral white matter in chronic alcoholics are uncertain. The present study examined the distribution of degenerating axons within cortical and subcortical tracts 1 week after recovery from early to late symptomatic stages of thiamine deficiency in the absence of ethanol in Sprague-Dawley rats. The brains of rats exposed to an early symptomatic stage of pyrithiamine-induced thiamine deficiency, 12-13 days of treatment, contained degenerating axons in corpus callosum, anterior commissure, external and internal capsules, optic and olfactory tracts, and fornix and mammillothalamic tracts. A dense pattern of degenerating axons was evident in layers III-IV of frontal and parietal cortex. Less intense and more evenly distributed degenerating axons were present in layers IV-VI of frontal, parietal, cingulate, temporal, retrosplenial, occipital, and granular insular cortex. Neuronal counts in mammillary body nuclei and areal measurements of the mammillary body were unchanged from controls and the thalamus was relatively undamaged. In animals reversed at later and more advanced symptomatic stages of thiamine deficiency, 14-15 days of treatment, degenerating axons were found in other cortical regions and hippocampus and there was extensive neuronal loss and gliosis within mammillary body and medial thalamus. These results demonstrate that a single episode of thiamine deficiency can selectively damage cortical white matter tracts while sparing the thalamus and mammillary body and may be a critical factor responsible for the pathological and behavioral changes observed in alcoholics without Wernicke's encephalopathy.

65 citations


Journal ArticleDOI
TL;DR: It is concluded that a low TPP concentration on two occasions is a better predictor of response to treatment than an isolated measurement and quality of life was enhanced by providing thiamine supplements.

63 citations


Journal Article
TL;DR: The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy and thiamine deficiency and Dietary guidelines for diabetic patients should emphasize a balanced diet.
Abstract: The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy. Of 200 consecutive patients, 100 were randomly allocated to treatment with both thiamine (25 mg/day) and pyridoxine (50 mg/day) group A and the rest group B to treatment with an identical tablet containing 1 mg/day each of thiamine and pyridoxine. Pain, numbness, paraesthesia and impairment of sensation and ankle in the legs were graded into none, mild, moderate or severe. Blood thiamine levels were measured using HPLC fluorimetry. Four weeks after starting treatment the grade was less than on the first visit in 88.9%, 82.5% and 89.7% of those whose worst symptoms were pain, numbness and paraesthesia respectively for group A compared with 11.1%, 40.5% and 39.4% respectively for group B. The severity of signs of peripheral neuropathy decreased in 48.9% of patients in group A compared with 11.4% in group B. The mean (s.e.) pre-treatment whole blood thiamine levels decreased with increasing severity of symptoms: 64.2 (2.81), 57.7 (3.25) and 52.2 (2.14) micrograms/l for those with mild, moderate and severe symptoms respectively (analysis of variance, p = 0.03). Diabetic peripheral neuropathy in Dar es Salaam is associated with thiamine deficiency. Dietary guidelines for diabetic patients should emphasize a balanced diet.

Journal ArticleDOI
TL;DR: The initial characterization of thiI is presented, a gene required for THZ synthesis that encodes a 483-amino-acid protein with a predicted molecular mass of 55 kDa and is not transcriptionally regulated by TPP.
Abstract: Thiamine pyrophosphate (TPP) is a required cofactor in Salmonella typhimurium that is generated de novo by the condensation of 4-amino-5-hydroxymethyl pyrimidine (HMP) pyrophosphate and 4-methyl-5-(beta-hydroxyethyl)-thiazole (THZ) monophosphate. The THZ and HMP moieties are independently synthesized, and labeling studies have demonstrated probable metabolic precursors to both. We present herein the initial characterization of thiI, a gene required for THZ synthesis. We show that thiI is a 1,449-bp open reading frame located at minute 9.65 on the S. typhimurium chromosome and that it encodes a 483-amino-acid protein with a predicted molecular mass of 55 kDa. Unlike genes in the thiamine biosynthetic operon at minute 90, thiI is not transcriptionally regulated by TPP.

Journal ArticleDOI
15 Oct 1997-Gene
TL;DR: Several alterations in the coding region were characterized that result in greatly reduced ability to transport thiamine, and the level of transporter mRNA was found to be rapidly and dramatically reduced by the addition ofThiamine to the growth medium.

Journal ArticleDOI
Abstract: Thiamine pyrophosphate (TPP) is synthesized de novo in Salmonella typhimurium and is a required cofactor for many enzymes in the cell. Five kinase activities have been implicated in TPP synthesis, which involves joining a 4-methyl-5-(beta-hydroxyethyl)thiazole (THZ) moiety and a 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) moiety. We report here identification of a 2-gene operon involved in thiamine biosynthesis and present evidence that the genes in this operon, thiMD, encode two previously identified kinases, THZ kinase and HMP phosphate (HMP-P) kinase, respectively. We further show that this operon belongs to the growing class of genes involved in TPP synthesis that are transcriptionally regulated by TPP. Our data are consistent with ThiM being a salvage enzyme and ThiD being a biosynthetic enzyme involved in TPP synthesis, as previously suggested.

Journal ArticleDOI
TL;DR: Clinically, THE AUTHORS presented as a severe refractory metabolic acidosis, preceded by ‘raspberry tongue’, and ophthalmologic and neurologic dysfunction, and the sites most affected were the periventricular structures and the thalamus.
Abstract: Wernicke's encephalopathy (WE) is a neuropsychiatric condition generally caused by acute thiamine deficiency and classically involves the triad of altered mentation, ataxia and ophthalmoplegia. It is most common among alcoholics, but several other causes have been identified, including total parenteral nutrition (TPN) use. We present eight cases of WE in patients undergoing allogeneic BMT, where thiamine deficiency was caused by a lack of vitamin supplementation during TPN administration. Clinically, WE presented as a severe refractory metabolic acidosis, preceded by 'raspberry tongue', and ophthalmologic and neurologic dysfunction. The sites most affected were the periventricular structures and the thalamus, and no mammilary bodies lesions were found.

Journal ArticleDOI
TL;DR: Transcription of the thiC operon is not regulated by thiamine or 2-methyl-4-amino-5-hydroxymethylpyrimidine and is only slightly repressed by 4- methyl-5-(beta-hydroxyethyl)thiazole.
Abstract: The characterization of a three-gene operon (the thiC operon) at 331 min, which is involved in thiamine biosynthesis in Bacillus subtilis, is described. The first gene in the operon is homologous to transcription activators in the lysR family. The second and third genes (thiK and thiC) have been subcloned and overexpressed in Escherichia coli. ThiK (30 kDa) catalyzes the phosphorylation of 4-methyl-5-(beta-hydroxyethyl)thiazole. ThiC (27 kDa) catalyzes the substitution of the pyrophosphate of 2-methyl-4-amino-5-hydroxymethylpyrimidine pyrophosphate by 4-methyl-5-(beta-hydroxyethyl)thiazole phosphate to yield thiamine phosphate. Transcription of the thiC operon is not regulated by thiamine or 2-methyl-4-amino-5-hydroxymethylpyrimidine and is only slightly repressed by 4-methyl-5-(beta-hydroxyethyl)thiazole.

Journal ArticleDOI
TL;DR: The interaction between the N1'-atom of the coenzyme and glutamic acid 51 strongly influences the catalytic activity but only moderately the binding of thecofactor to the apoenzyme and the substrate activation rate.
Abstract: We investigated the importance of the interaction between the N1‘-atom of the cofactor thiamine diphosphate and glutamic acid residue 51 in pyruvate decarboxylase (EC 4.1.1.1). The yeast wild type gene PDC1 and the respective mutant genes (E51Q and E51A) were expressed in Escherichia coli. The three enzymes were purified to homogeneity. They comigrated as a single band during silver-stained SDS/PAGE with a molecular mass of 60 000 Da. A molecular mass of 61 200 ± 200 Da was determined by mass spectrometry for the subunit. The native enzyme is a homotetramer as demonstrated by gel filtration experiments. Near- and far-UV CD spectra showed no significant differences for the apoenzyme of the wild type and the mutants. Slight differences in the rate of thiamine diphosphate binding to the apoprotein component were observed between the wild type and the E51Q PDC by CD spectroscopy. Compared to the wild type enzyme, thiamine diphosphate binding at the E51A mutant apoprotein is very slow. Only 0.04% of the cataly...

Journal ArticleDOI
TL;DR: The needs are emphasized to supplement TPN with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements; to monitor the patients routinely measuring serumThiamine concentration and erythrocyte transketolase activity during TPN; and to intravenously replenish using high-dose Thiamine simultaneously with the manifestation of signs and symptoms of lactic acidosis.

Journal ArticleDOI
TL;DR: No difference in blood thiamine diphosphate levels between Swedish Caucasian patients with congestive heart failure treated with furosemide and patients without heart failure is found.
Abstract: . Yue Q-Y, Beermann B, Lindstrom B, Nyquist 0 (Huddinge University Hospital, Huddinge, and the Medical Product Agency, Uppsala, Sweden). No difference in blood thiamine diphosphate levels between Swedish Caucasian patients with congestive heart failure treated with furosemide and patients without heart failure. Intern Med 1997; 242:49 1-49 5. Objectives: To determine whether furosemide treatment in congestive heart failure (CHF) patients is associated with thiamine deficiency. Design: Patients without heart failure and without diuretic treatment were included to compare with patients with CHF belonging to New York Heart Association (NYHA) functional class I1 and 111-IV, respectively, and receiving furosemide therapy. Setting: All patients were recruited from the emergency ward of the cardiology section, Huddinge University Hospital, where they were admitted due to CHF or acute myocardial infarction. Subjects: Ninety-nine patients were included from whom a blood sample was taken, as well as routine admission blood samples for the analysis of thiamine diphosphate (TPP) concentrations: Patients taking vitamin preparations were excluded. Main outcome measures: Blood TPP concentrations were measured by high performance liquid chromatography (HPLC) and compared between the patient groups by the use of ANOVA. Results: No significant difference was found between the groups in blood TPP concentrations. Conclusions: Thiamine deficiency may not be a complication of furosemide treatment in the studied Swedish patient population.

Journal ArticleDOI
TL;DR: There is a need for education of doctors who treat alcohol-dependent patients, in order to ensure appropriate use of parenteral thiamine in prophylaxis and treatment of Wernicke's encephalopathy.
Abstract: Wernicke's encephalopathy, a disorder with significant mortality and high morbidity, is common amongst alcohol-dependent patients. Thiamine deficiency appears to play a key role in its aetiology, and parenteral high-dose thiamine is effective in prophylaxis and treatment. Unfortunately, reports of rare anaphylactoid reactions have led to a dramatic reduction in the use of parenteral thiamine, and it is possible that this change in treatment has led, or will lead, to an increase in morbidity and mortality. There is a need for education of doctors who treat alcohol-dependent patients, in order to ensure appropriate use of parenteral thiamine in prophylaxis and treatment of this disorder.

Journal ArticleDOI
TL;DR: Rat heart cells in culture were found to be a unique model for studying biochemical and pharmacological aspects of thiamine deficiency and all effects were reversible ifThiamine was supplied before the initiation of the degeneration processes.

Journal ArticleDOI
TL;DR: It is suggested that chronically applied thiamine, pyridoxine and nicotinamide protect retinal neurons against glutamate cytotoxicity.

Journal ArticleDOI
TL;DR: Results of phenotypic analyses suggested that a defect in Sdh decreased the thiamine requirement of Salmonella typhimurium, and this reduced requirement correlated with levels of succinyl-coenzyme A (succinyl-CoA), which is synthesized in aThiamine pyrophosphate-dependent reaction.
Abstract: Mutants lacking the first enzyme in de novo purine synthesis (PurF) can synthesize thiamine if increased levels of pantothenate are present in the culture medium (J. L. Enos-Berlage and D. M. Downs, J. Bacteriol. 178:1476-1479, 1996). Derivatives of purF mutants that no longer required pantothenate for thiamine-independent growth were isolated. Analysis of these mutants demonstrated that they were defective in succinate dehydrogenase (Sdh), an enzyme of the tricarboxylic acid cycle. Results of phenotypic analyses suggested that a defect in Sdh decreased the thiamine requirement of Salmonella typhimurium. This reduced requirement correlated with levels of succinyl-coenzyme A (succinyl-CoA), which is synthesized in a thiamine pyrophosphate-dependent reaction. The effect of succinyl-CoA on thiamine metabolism was distinct from the role of pantothenate in thiamine synthesis.

Journal ArticleDOI
TL;DR: The cloned gene c-thi1, homologous to yeast and plant genes encoding for an enzyme belonging to the pathway of thiamine biosynthesis, increased gradually in the peel during natural fruit maturation and in response to ethylene.
Abstract: Maturing citrus fruit undergo pigment changes which can be enhanced by exogenous ethylene. In order to identify genes induced by ethylene in citrus fruit peel, we cloned the gene c-thi1. mRNA corresponding to c-thi1 increased gradually in the peel during natural fruit maturation and in response to ethylene. GA3 pretreatment reduced the inductive effect of ethylene. Levels of c-thi1 increased also in juice sacs but the effect of ethylene was much less prominent. c-thi1 is homologous to yeast and plant genes encoding for an enzyme belonging to the pathway of thiamine biosynthesis. The data suggest that thiamine is involved in citrus fruit maturation.

Journal ArticleDOI
TL;DR: Both groups showed a significant decrease in scores on the Abnormal Involuntary Movement Scale (TD) and the Simpson-Angus Neurological Rating Scale (parkinsonism) while on A + T, unrelated to age, gender, diagnosis, or maintenance medications.
Abstract: The effects of the administration of acetazolamide and thiamine (A + T) on the symptoms of tardive dyskinesia (TD) and parkinsonism of 8 elderly and 25 younger chronic hospitalized mental patients were examined in a placebo-controlled, double-blind, counterbalanced two-period crossover study with initial baselines and intervening washout periods. All patients were maintained on their prestudy psychoactive and anti-Parkinson medications, without alteration, throughout the study. The elderly group received 1.5 g acetazolamide and thiamine per day in three divided doses for 3 weeks. The younger group received 1.5 g thiamine and 2.0 g acetazolamide per day in divided doses for 2 months. Both groups showed a significant decrease in scores on the Abnormal Involuntary Movement Scale (TD) and the Simpson-Angus Neurological Rating Scale (parkinsonism) while on A + T. The A + T effects were unrelated to age, gender, diagnosis, or maintenance medications. (J Clin Psychopharmacol 1997;17:190-193).

Journal ArticleDOI
TL;DR: Results are consistent with the suggestion that aspartate 155 is an important coordination site for magnesium, and binding of cofactor by wild type apo-transketolase required the presence of magnesium.

Journal ArticleDOI
TL;DR: A cat with allergic dermatitis was fed a diet of fresh meat and a multi-vitamin supplement for 38 days to exclude food allergy as a cause of its dermatopathy, which resulted in the death of the cat as a result of acute thiamine deficiency.
Abstract: A cat with allergic dermatitis was fed a diet of fresh meat and a multi-vitamin supplement for 38 days to exclude food allergy as a cause of its dermatopathy. The cat died as a result of acute thiamine deficiency, which was caused by inac-tivation of thiamine by the preservative, sulphur dioxide. The continuing undeclared usage of sulphites in the Australian pet food industry is discussed.

Journal ArticleDOI
TL;DR: A 65-year-old man with a history of chronic alcoholism had erectile dysfunction 1 year in duration as well as symptoms of retrograde ejaculation and a weak stream and vitamin B supplementation resulted in cure.

Journal ArticleDOI
TL;DR: Epidemics of an acute ataxic syndrome occur annually in the rainy season in parts of south-western Nigeria, characterized by intention tremors, ataxia and varying levels of impaired consciousness, following a carbohydrate meal.
Abstract: Epidemics of an acute ataxic syndrome occur annually in the rainy season in parts of south-western Nigeria, characterized by intention tremors, ataxia and varying levels of impaired consciousness, following a carbohydrate meal (Wright and Morley, 1958; Coakham, 1972; Osuntokun, 1972). This syndrome was first reported from amongst the Ijeshas living in and around Ilesha, a town in the northern part of the rain forest zone of Western Nigeria, whence the syndrome was first described (Wright and Morley, 1958); hence the pseudonym \"Ijesha shakes\". Epidemics have however also been reported from several other parts of Western Nigeria (Osuntokun, 1972; Adamolekun and Ibikunle, 1994).