Showing papers on "Thiamine published in 1984"
TL;DR: Changes in the neurological signs during pyrithiamin-induced thiamin deficiency and in recovery paralleled the reversible damage to a mitochondrial enzyme and impairment of glucose oxidation and acetylcholine synthesis.
Abstract: To clarify the enzymatic mechanisms of brain damage in thiamin deficiency, glucose oxidation, acetylcholine synthesis, and the activities of the three major thiamin pyrophosphate (TPP) dependent brain enzymes were compared in untreated controls, in symptomatic pyrithiamin-induced thiamin-deficient rats, and in animals in which the symptoms had been reversed by treatment with thiamin. Although brain slices from symptomatic animals produced 14CO2 and 14C-acetylcholine from [U-14C]glucose at rates similar to controls under resting conditions, their K+-induced-increase declined by 50 and 75%, respectively. In brain homogenates from these same animals, the activities of two TPP-dependent enzymes transketolase (EC 2.2.1.1) and 2-oxoglutarate dehydrogenase complex (EC 1.2.4.2, EC 2.3.1.61, EC 1.6.4.3) decreased 60-65% and 36%, respectively. The activity of the third TPP-dependent enzyme, pyruvate dehydrogenase complex (EC 1.2.4.1, EC 2.3.1.12, EC 1.6.4.3) did not change nor did the activity of its activator pyruvate dehydrogenase phosphate phosphatase (EC 3.1.3.43). Although treatment with thiamin for seven days reversed the neurological symptoms and restored glucose oxidation, acetylcholine synthesis and 2-oxoglutarate dehydrogenase activity to normal, transketolase activity remained 30-32% lower than controls. The activities of other TPP-independent enzymes (hexokinase, phosphofructokinase, and glutamate dehydrogenase) were normal in both deficient and reversed animals.
138 citations
TL;DR: Cerebral regions showing significant acidosis during thiamine deficiency coincided largely with those known to be histologically vulnerable and those previously reported to show a focal rise in local cerebral glucose utilization between days 11 and 14 of thienine deficiency, indicating one mechanism contributing to the selective histological vulnerability in this model.
Abstract: Regional cerebral pH was determined autoradiographically using carbon 14-labeled dimethyloxazolidinedione in normal rats, following various durations of thiamine deficiency and replenishment with thiamine when the clinical sequelae of the deficiency appeared. In our model the clinical sequelae of thiamine deficiency (opisthotonus) appeared on the average on day 18. Regional cerebral pH on day 12 was comparable to that in controls and ranged between 7.02 +/- 0.03 and 7.09 +/- 0.03 (mean +/- SEM) in gray matter structures. On day 14 the pH in the inferior colliculus was 6.85 +/- 0.08 and relative acidosis also appeared in thalamic structures. At opisthotonus the pH was 6.48 +/- 0.17 in the mamillary body, 6.43 +/- 0.14 in the vestibular nucleus, and 6.36 +/- 0.14 in the medial dorsal nucleus of the thalamus (p less than 0.01). One dose of thiamine replenishment at this stage transiently raised the pH in the inferior colliculus to 7.25 +/- 0.19 and in the medial dorsal nucleus to 7.20 +/- 0.13 (p less than 0.01). Cerebral regions showing significant acidosis during thiamine deficiency coincided largely with those known to be histologically vulnerable and those previously reported to show a focal rise in local cerebral glucose utilization between days 11 and 14 of thiamine deficiency. This focal acidosis shown to occur in thiamine deficiency may be one mechanism contributing to the selective histological vulnerability in this model.
96 citations
TL;DR: A case of unexplained anemia in association with diabetes mellitus and sensorineural deafness and the anemia responded only to pharmacologic closes of thiamine.
Abstract: IN 1969 Rogers et al. described a case of unexplained anemia in association with diabetes mellitus and sensorineural deafness.1 The anemia responded only to pharmacologic closes of thiamine. Anothe...
91 citations
TL;DR: Empirical treatment with thiamine proved to be a cure for the disorder, for it was acute pernicious or fulminating beriberi, a cause of lacticacidosis.
81 citations
TL;DR: Oral administration of lipoic acid 25 to 50 mg/kg produced dramatic improvement in lactic and pyruvic acidemia, which has continued for 2 years and which has been accompanied by clinical improvement.
72 citations
TL;DR: It is concluded that the mitochondrial abnormalities resulting from thiamine deficiency are secondary to depression ofThiamine-mediated enzyme activity, rather than from a putative role of Thiamine in chemiosmotic coupling, and that the resulting abnormalities in ATP synthesis and perhaps in glutamate catabolism result in the irreversible neurologic defect seen in this disease.
Abstract: Thiamine deficiency causes Wernicke's encephalopathy, although the precise mechanism is unknown. We used a low-thiamine diet in conjunction with a thiamine analog, pyrithiamine, as a model of severe thiamine deficiency in rats. We investigated the function of intact, coupled mitochondria isolated from both brain and liver. State 4 respiration did not change in the thiamine-deficient animals. Brain state 3 rates fell in thiamine-deficient animals when pyruvate/malate, alpha-ketoglutarate, or glutamate were used as substrate. Liver state 3 rates were depressed only when pyruvate/malate was substrate. Activities of brain and liver pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex were depressed in the thiamine-deficient group. We conclude that the mitochondrial abnormalities resulting from thiamine deficiency are secondary to depression of thiamine-mediated enzyme activity, rather than from a putative role of thiamine in chemiosmotic coupling, and that the resulting abnormalities in ATP synthesis and perhaps in glutamate catabolism result in the irreversible neurologic defect seen in this disease.
54 citations
TL;DR: Significantly elevated levels of vitamin B12, riboflavin, biotin, and pantothenate were present in the patients, while thiamin, vitamin B6, nicotinate, and ascorbate were not significantly different from controls.
52 citations
TL;DR: The shortest turnover time of TPP was found in the cerebellum, while the sciatic nerve exhibited the fastest renewal of T and TMP, suggesting that its function might be associated to a rapid conversion into chemically different forms.
49 citations
45 citations
01 Jan 1984
42 citations
TL;DR: Thiamine transport system in rat liver cells is closely connected with thiamine pyrophosphokinase, which accelerates the uptake rat of Thiamine by pyroph phosphorylation at physiological concentrations of thiamines.
TL;DR: The method was found suitable for the determination of thiamine compounds in excitable tissues such as nerves and electric organs as well as in proteins extracted from membranes of these organs and may be useful to study the role ofThiamine in the electrical activity of these tissues at the molecular level.
TL;DR: The overall transport rate of TMP was on average 5-10 times as low as that of T and also showed a saturable and a non-saturable component that was most efficient in the cerebral cortex.
TL;DR: Results suggest that thiamine deficiency is unusual in well nourished patients with alcoholic liver disease, and conclusions from studies using indirect assays on the prevalence and mechanisms of thiamines deficiency in liver diseases may not be valid.
Abstract: Thiamine state was investigated in patients with alcoholic liver disease, patients with various non-alcoholic liver diseases, and controls using a direct technique (thiochrome assay) to measure thiamine, thiamine monophospate, and the active coenzyme thiamine pyrophosphate in whole blood after isolating the fractions by ion exchange chromatography. Overall nutrition was similar in all groups as assessed by anthropometry, and no patient had clinical evidence of thiamine deficiency. There was no significant difference among the groups in mean concentration of any form of thiamine. The scatter was much greater in patients with alcoholic liver disease but only 8.7% had biochemical thiamine deficiency (defined as a blood concentration of the active coenzyme greater than 2 SD below the mean control value). An unexpected finding was of abnormally high total thiamine concentrations (greater than 2 SD above the mean control value) in 17.4% of patients with alcoholic liver disease, the highest concentrations being found in two patients with severe alcoholic hepatitis and cirrhosis. The ratio of phosphorylated to unphosphorylated thiamine was calculated as an index of phosphorylation and, although the mean did not differ significantly among the groups, the range was greatest in alcoholic liver disease. The lowest ratios occurred in the two patients with severe alcoholic hepatitis, but neither had evidence of thiamine pyrophosphate deficiency. Contrary to studies using indirect assay techniques, these results suggest that thiamine deficiency is unusual in well nourished patients with alcoholic liver disease. The new finding of unexpectedly high thiamine concentrations in some patients may be due to abnormalities of hepatic storage or release in liver disease, particularly in severe alcoholic hepatitis. There was no convincing evidence of impaired thiamine phosphorylation in any patients with liver disease. Conclusions from studies using indirect assays on the prevalence and mechanisms of thiamine deficiency in liver diseases may not be valid.
TL;DR: Gastric partitioning is a safe and effective alternative to jejunoileal bypass in the control of morbid obesity, however, severe permanent neurologic deficits, probably related to thiamine deficiency, may occur.
Abstract: Gastric partitioning has been proposed as an alternative to jejunoileal bypass for the control of morbid obesity because of the relative ease of performance and the lack of metabolic complications From our series of 250 patients who underwent gastric partitioning, one of them developed a neurologic syndrome consistent with Wernicke's disease The clinical findings were characterized by ataxia, confusion, impaired extra-ocular movements with diplopia, and weakness A second patient with a similar condition was referred to us for evaluation and treatment Pretreatment thiamine levels were normal in one case and revealed thiamine deficiency in the second The study group of 15 patients had thiamine and red cell transketolase levels determined before, 6 wk, and 1 yr after gastric partitioning A significant drop in values was seen at 6 wk postoperatively Gastric partitioning is a safe and effective alternative to jejunoileal bypass in the control of morbid obesity However, severe permanent neurologic deficits, probably related to thiamine deficiency, may occur
TL;DR: The death rate of Methanobacterium thermoautotrophicum strain Marburg upon exposure to N-methyl-N′-nitro-N-nitrosoguanidine under anaerobic conditions was of the same order of magnitude as the death rates that have been reported for Escherichia coli.
Abstract: The death rate ofMethanobacterium thermoautotrophicum strain Marburg upon exposure toN-methyl-N′-nitro-N-nitrosoguanidine under anaerobic conditions was of the same order of magnitude as the death rates that have been reported forEscherichia coli. Cultures of the methanogenic bacterium, mutagenized by nitrosoguanidine-treatment and grown under non-selective conditions, yielded mutants resistant toDL-ethionine (30 mM) or to 2-bromoethane sulfonic acid (3.8 mM). No mutants were observed in untreated controls. Among 1500 clones obtained from nitrosoguanidine-treated cell suspensions there were 6 mutants requiring a single growth factor each, namelyl-leucine,l-phenylalanine, thiamine (2 mutants) or adenosine (2 mutants). Three mutant-strains were studied in more detail. They were genetically stable (no revertants among 109 cells), and wild type growth rates were restored by 5 mml-leucine, 0.4 mM adenosine and 0.03 mM thiamine, respectively.
TL;DR: A thiamine-binding protein was purified from the extract of rice bran acetone powder by conventional procedures of acid precipitation, a series of column chromatography on DEAE-Sephadex A-50 andDEAE-cellulose, and gel filtration of SephadeX G-200, suggesting that the protein is composed of two identical subunits.
Abstract: A thiamine-binding protein was purified from the extract of rice bran acetone powder by conventional procedures of acid precipitation, a series of column chromatography on DEAE-Sephadex A-50 and DEAE-cellulose, and gel filtration of Sephadex G-200. The purified thiamine-binding protein was nearly homogeneous as judged by disc gel electrophoresis and the molecular weight was estimated to be 94,000 by gel filtration on Sephadex Gn-200 and 50,000 by sodium dodecylsulfate (SDS) gel electrophoresis, suggesting that the protein is composed of two identical subunits. The apparent Kd and Bmax of the binding for [14C]thiamine was 0.44 +/- 0.05 microM and 17.2 +/- 0.7 nmol/mg of protein, respectively. The optimal pH for the binding is between 8.0 and 9.0. From the competition experiment using several thiamine derivatives, high binding specificity of the protein for thiamine was presumed.
TL;DR: The rationale for various forms of therapy is reviewed, including the treatment aimed at correcting the "hypermetabolic state" in alcoholics ad the pitfalls of excess nutrient administration (particularly as it pertains to pyridoxine, vitamin A and amino acids).
Journal Article•
TL;DR: It was demonstrated that chloroethylthiamine is accumulated in nonproliferating cells of Saccharomyces cerevisiae by the same transport mechanism as for thiamine and dimethialium.
Abstract: The separate determination of anticoccidial thiamine analogs such as chloroethylthiamine and dimethialium, and thiamine was achieved by reversed-phase high-performance liquid chromatography after conversion to the corresponding thiochromes by alkaline oxidation. Using this method, it was demonstrated that chloroethylthiamine is accumulated in nonproliferating cells of Saccharomyces cerevisiae by the same transport mechanism as for thiamine and dimethialium.
TL;DR: The results suggest that the d-DTP synthesizing enzyme plays an important role in the biosynthesis of the thiazole ring of thiamine in vivo.
Abstract: A new enzymatic acyloin-type condensation between pyruvate (or acetoin or methylacetoin) and D-glyceraldehyde was found to be catalyzed by cell-free extracts of a transketolase mutant of Bacillus pumilus IFO 12089. The reaction product (1) was isolated and determined to be 1-deoxy-D-threo-pentulose (d-DTP), which is considered to be a precursor of the five-carbon unit of the thiazole ring thiamine. 1-Deoxy-L-threo-pentulose (l-DTP, 2) was synthesized similarly when l-glyceraldehyde was used instead of D-glyceraldehyde. The configurations of 1 and 2 were confirmed by reduction to the corresponding 1-deoxy-pentitols.Similar enzyme activities were also detected in cell-free extracts of all the wild-type strains tested of bacteria, actinomycetes, yeasts, and molds. These results suggest that the d-DTP synthesizing enzyme plays an important role in the biosynthesis of the thiazole ring of thiamine in vivo.
TL;DR: The PA value, representing the permeability of the blood-brain barrier to14C-sucrose, was significantly increased whether urethane or ethanol was used as anaesthetic, and Barrier function was normalised by injecting thiamine into deficient rats for just 3 days before biopsy.
Abstract: Rats maintained on a thiamine-deficient diet for 38 days lost weight and showed neurological symptoms. The PA value, representing the permeability of the blood-brain barrier to14C-sucrose, was significantly increased whether urethane or ethanol was used as anaesthetic. This increase was prevented by giving rats on the same diet injections of thiamine twice weekly. Barrier function was normalised by injecting thiamine into deficient rats for just 3 days before biopsy. The brains of the thiamine-deficient rats were stained by the Fink-Heimer method but showed no degenerating axons except for silver grains in the glomeruli of the olfactory bulb. Other rats were maintained on the same diet for 38 days and additionally exposed to ethanol vapour for 16 h per day. This resulted in a similar loss of weight but a greater leakage of the blood-brain barrier. The latter was normalised by a thiamine injection only 24 h before biopsy, but was not reduced by withdrawal of ethanol for 3 days before biopsy. Axonal degeneration was present in the olfactory glomeruli. However, no lesions or extravasated blood cells were seen in any brains, there was no change in brain water indicative of oedema and no degeneration in retina, distal peripheral nerves or leg muscles. The relation of these and other experimental findings to alcohol-related brain damage is considered.
Journal Article•
TL;DR: A sensitive method for the measurement of thiamine pyrophosphate in whole blood and erythrocytes, using a straight-phase high performance liquid chromatography (HPLC) is described, showing reproducibility and accuracy of the assay.
Abstract: A sensitive method for the measurement of thiamine pyrophosphate in whole blood and erythrocytes, using a straight-phase high performance liquid chromatography (HPLC), is described. The method was based on sample extraction with trichloracetic acid, conversion of the vitamer to the corresponding high fluorescent thiochrome ester, and separation and measurement of the derivative by HPLC. Evidence for reproducibility and accuracy of the assay is presented. Data indicating the thiamine pyrophosphate levels to be expected in blood and erythrocytes of healthy humans are included.
TL;DR: A modified procedure for the preparation of transketolase from erythrocytes by dialysis and columnion-exchange resin chromatography is described in this paper, where changes have been made in the resin used, the column dimensions and the elution procedure so as to separate the enzyme with improved resolution, prepare the apoenzyme free of thiamine pyrophosphate and study the kinetics of its activation or reactivation by the coenzyme.
Abstract: A modified procedure for the preparation of transketolase from erythrocytes by dialysis and columnion-exchange resin chromatography is described. Changes have been made in the resin used, the column dimensions and the elution procedure so as to separate the enzyme with improved resolution, prepare the apoenzyme free of thiamine pyrophosphate and study the kinetics of its activation or reactivation by the coenzyme. On the basis of the elution profile of the enzyme activity from the chromatographic column, two different samples of the transketolase have been isolated, which differ not only in their isoelectric properties, but also in the proportion of the transketolase present in the apoenzyme form. Not only do the apoenzymes isolated from each of the two fractions differ in the way in which they recombine with thiamine pyrophosphate but kinetic analysis of the results shows that each fraction contains at least two variants of transketolase differing in their affinity for thiamine pyrophosphate. Three, probably four, separate variants have been identified which differ in their affinities for thiamine pyrophosphate over a range greater than 104. It is concluded that these two fractions of the enzyme must contain different subsets of the eight isoenzymes of transketolase of differing isoelectric points and that some of these isoenzymes must differ also in their affinity for the coenzyme. The implications of these findings for the Blass and Gibson hypothesis about the pathogenesis of the Wernicke-Korsakoff syndrome are considered.
TL;DR: The results of this paper suggested that muricide induced by thiamine deficiency is not mediated by the central histaminergic system, but pharmacologically characterized by antidepressants, antihistamines and histamine synthesis inhibitors.
TL;DR: Thiamine serves as a cofactor for glucose metabolism in the glycolytic and pentose phosphate pathways and its deficiency produces a nutritional neurologic disorder, the Wernicke-Korsakoff synd...
Abstract: Excerpt Thiamine serves as a cofactor for glucose metabolism in the glycolytic and pentose phosphate pathways. Its deficiency produces a nutritional neurologic disorder, the Wernicke-Korsakoff synd...
TL;DR: Thiamine derivatives could well play a specific role in the molecular aspects of bioelectrogenesis, an interpretation that could help explain the neurological symptoms observed in human pathology as well as in animals experimentally rendered deficient in vitamin Bl.
Abstract: The results show that thiamine derivatives are copurified with the specific proteins forming the Na+ channel in conducting membranes. Therefore, thiamine derivatives could well play a specific role in the molecular aspects of bioelectrogenesis , an interpretation that could help explain the neurological symptoms observed in human pathology as well as in animals experimentally rendered deficient in vitamin B1.
TL;DR: Three models are compared describing cooperative phenomena in enzymatic reactions in order to explain sigmoidal saturation curves found with the pyruvate dehydrogenase complex from Escherichia coli: the concerted model, the sequential model, and the slow transition model.
TL;DR: Thiamine added to a vitamin B6-free medium was accumulated in the free form in Saccharomyces yeast cells, and caused growth inhibition and respiratory deficiency under aerobic conditions, and was suggested to be caused by a thiamine-enhanced glucose effect.
Abstract: Thiamine added to a vitamin B6-free medium was accumulated in the free form in Saccharomyces yeast cells, and caused growth inhibition and respiratory deficiency under aerobic conditions. The thiamine-induced respiratory deficiency occurred as the result of a sequence of events as follows: (1) a decrease in vitamin B6 content, (2) a reduction in the activity of δ-aminolevulinate synthase, (3) heme deficiency, (4) cytochrome deficiency, and (5) respiratory deficiency. However, the growth inhibition was shown to be partially due to the respiratory deficiency, and the participation of some other events caused by the thiamine-induced vitamin B6 deficiency was suggested. The cytochrome deficiency also caused alteration in lipid composition; unsaturated fatty acid content was decreased and sterol composition was changed. Associated with the respiratory deficiency, the activity of NAD-linked glutamate dehydrogenase was decreased. In contrast, the NADP-linked enzyme activity was markedly increased. It was suggested that this increase was not caused by the respiratory deficiency but by a thiamine-enhanced glucose effect. The thiamine-grown cells showed an altered amino acid pool. Reflecting the respiratory deficiency, the thiamine-grown cells showed elevated activities of glycolysis and ethanol production. It was, however, suggested that the glycolytic rate was not determined by-phosphofructokinase activity, and ethanol production was controlled independently of glycolytic activity in the thiamine-supplemented culture.