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PubMed1979

Thiamine deficiency in general hospital patients.

The production of sedoheptulose-7-phosphate in the red blood cells of 15 patients was found to be below the suggested normal value. This intermediate product of glucose metabolism is the result of transketolase activity for which thiamine pyrophosphate is one of the co-factors. Without thiamine, the transketolase reaction is inhibited. Some nonlocalizing symptoms, perhaps previously thought due to hypoglycemia, may be occasioned by faulty glucose metabolism at the cellular level from a relative lack of thiamine.

Erythrocytes↗

PubMed1997

Effects of B vitamins on glutamate-induced neurotoxicity in retinal cultures.

The effects of B vitamins on glutamate-induced neurotoxicity were examined using primary cultures obtained from the rat retina. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free media for 1 h. Glutamate cytotoxicity was reduced in the cultures that had been maintained in thiamine-, pyridoxine- or nicotinamide-containing medium before the exposure to glutamate. Glutamate cytotoxicity was also reduced by chronic application of thiamine pyrophosphate and pyridoxal phosphate, which are active coenzyme forms of thiamine and pyridoxine, respectively. By contrast, chronic application of riboflavin, pantothenate, biotin, folic acid and inositol did not affect glutamate cytotoxicity. None of the B vitamins tested had any effect on glutamate cytotoxicity when added only during the exposure to glutamate. These findings suggest that chronically applied thiamine, pyridoxine and nicotinamide protect retinal neurons against glutamate cytotoxicity.

Animals↗

PubMed1979

Transketolase activity in psychiatric patients.

The thiamine status of 42 physically healthy nonalcoholic psychiatric inpatients was evaluated by measuring transketolase activity in a hemolysate of their red blood cells, before and after addition of thiamine pyrophosphate to the hemolysate. Sixteen patients (38%) showed evidence of thiamine deficiency. Five of these patients had received thiamine-containing vitamins for a period of from 2 fo 47 days prior to testing, suggesting that poor nutrition may not fully account for the thiamine deficiency observed.

Adolescent↗

PubMedDate not supplied

[Thiamine triphosphate content of the liver of albino rats with different levels of thiamine].

Content of thiamine triphosphate (TTP) was studied in rat liver tissue under conditions of normal state, thiamine deficiency and after loading with thiamine. The concentration of TTP in hepatocytes of control animals was found to be 3.2-3.6 micrograms/g, corresponding to 40% of the total thiamine pool in the cells. The TTP appears to serve as a reserve of vitamin B1 deposited in mitochondria of the cells in which the biosynthesis of thiamine pyrophosphate of their own did not take place. Administration of thiamine did not induce the TTP overproduction in hepatocytes; the content of TTP was maintained in the mitochondria of the hepatocytes at the constant level.

Animals↗

PubMed1987

Effect of thiamine on the excretion of subcutaneously injected lead in rats.

The effect of thiamine on the excretion of lead in feces was investigated using rats injected subcutaneously with lead acetate and thiamine pyrophosphate. The amount of lead excreted increased with the amounts of thiamine administered, while lead concentrations in blood, liver and femur also increased. The amount of lead excreted in feces decreased, however, with administration of oxythiamine and vanadium. These results suggest that excretion of lead in feces is enhanced by thiamine and that it promotes evacuation of lead from the body.

Animals↗

PubMed1979

Effect of oral contraceptive agents on thiamin status.

A cross-sectional and follow up study of oral contraceptive agent (OCA) users revealed no adverse effects of OCA on erythrocyte transketolase activity (ETK) or thiamin pyrophosphate effect (TPP effect). In the cross-sectional study group, thiamin intake was below the recommended in only 19.2 per cent subjects and thiamin intake/100 kcal/day revealed a significant negative correlation with TPP effect. Routine prophylactic administration of thiamin was not indicated in OCA users.

Adolescent↗

PubMed1990

Thiamin transport by human erythrocytes and ghosts.

Thiamin transport in human erythrocytes and resealed pink ghosts was evaluated by incubating both preparations at 37 or 20 degrees C in the presence of [3H]-thiamin of high specific activity. The rate of uptake was consistently higher in erythrocytes than in ghosts. In both preparations, the time course of uptake was independent from the presence of Na+ and did not reach equilibrium after 60 min incubation. At concentrations below 0.5 microM and at 37 degrees C, thiamin was taken up predominantly by a saturable mechanism in both erythrocytes and ghosts. Apparent kinetic constants were: for erythrocytes, Km = 0.12, 0.11 and 0.10 microM and Jmax = 0.01, 0.02 and 0.03 pmol.microliter-1 intracellular water after 3, 15, and 30 min incubation times, respectively; for ghosts, Km = 0.16 and 0.51 microM and Jmax = 0.01 and 0.04 pmol.microliter-1 intracellular water after 15 and 30 min incubation times, respectively. At 20 degrees C, the saturable component disappeared in both preparations. Erythrocyte thiamin transport was not influenced by the presence of D-glucose or metabolic inhibitors. In both preparations, thiamin transport was inhibited competitively by unlabeled thiamin, pyrithiamin, amprolium and, to a lesser extent, oxythiamin, the inhibiting effect being always more marked in erythrocytes than in ghosts. Only approximately 20% of the thiamin taken up by erythrocytes was protein- (probably membrane-) bound. A similar proportion was esterified to thiamin pyrophosphate. Separate experiments using valinomycin and SCN- showed that the transport of thiamin, which is a cation at pH 7.4, is unaffected by changes in membrane potential in both preparations.

Biological Transport↗

PubMed1981

Nature of the thiamin-binding protein from chicken egg yolk.

A simple, rapid and efficient procedure for the purification of thiamin-binding protein from chicken egg yolk was developed. The method involved removal, by exclusion, of lipoproteins from DEAE-cellulose and subsequent elution of water-soluble proteins held on the ion-exchanger with 1 M-NaCl, followed by treatment of the eluted protein fraction with an aqueous suspension of dextran/charcoal to generate apoprotein from the holoprotein. The resultant protein fraction was subjected to bioaffinity chromatography on thiamin pyrophosphate--AE (aminoethyl)-Sepharose. The protein eluted specifically with 10 microM-thiamin at pH 7.0, was homogeneous by the criteria of polyacrylamide-gel disc electrophoresis, had a mol.wt. of 38 000 +/- 2000 and was not a glycoprotein. The purified thiamin-binding protein specifically interacted with riboflavin-binding protein with no detectable deleterious affect on its (14C)thiamin-binding capacity. The protein bound [14C]thiamin with a molar ratio of 1.0, with dissociation constant (Kd) 0.41 microM. This protein-ligand interaction was inhibited by thiamin analogues and antagonists. The absorption spectrum of the protein in the presence of thiamin exhibited significant hypochromism at the 278 nm band, indicating the involvement of aromatic amino acid residues of the protein, during its binding to the ligand. The protein cross-reacted with the monospecific antiserum to egg-white thiamin-binding protein, showing thereby that thiamin-binding proteins present in chicken egg yolk and white are the products of the same structural gene.

Animals↗

PubMed1952

Crystalline inorganic pyrophosphatase isolated from baker's yeast.

Crystalline inorganic pyrophosphatase has been isolated from baker's yeast. The crystalline enzyme is a protein of the albumin type with an isoelectric point near pH 4.8. Its molecular weight is of the order of 100,000. It contains about 5 per cent tyrosine and 3.5 per cent tryptophane. It is most stable at pH 6.8. The new crystalline protein acts as a specific catalyst for the hydrolysis of inorganic pyrophosphate into orthophosphate ions. It does not catalyze the hydrolysis of the pyrophosphate radical of such organic esters as adenosine di- and triphosphate, or thiamine pyrophosphate. Crystalline pyrophosphatase requires the presence of Mg, Co, or Mn ions as activators. These ions are antagonized by calcium ions. Mg is also antagonized by Co or Mn ions. The rate of the enzymatic hydrolysis of inorganic pyrophosphate is proportional to the concentration of enzyme and is a function of pH, temperature, concentration of substrate, and concentration of activating ion. The approximate conditions for optimum rate are: 40 degrees C. and pH 7.0 at a concentration of 3 to 4 x 10(-3)M Na(4)P(2)O(7) and an equivalent concentration of magnesium salt. The enzymatic hydrolysis of Na(4)P(2)O(7) or K(4)P(2)O(7) proceeds to completion and is irreversible under the conditions at which hydrolysis is occurring. Details are given of the method of isolation of the crystalline enzyme.

Diphosphates↗

PubMed1994

Thiamine deficiency in hospitalized elderly patients.

Necropsy studies suggest that thiamine deficiency is underdiagnosed in life, in part because the classical clinical presentations are uncommon. Anecdotal reports suggest that thiamine deficiency may contribute to the development of delirium, heart failure and peripheral neuropathy in elderly patients, but little systematic research has been reported. We examined thiamine levels in 36 consecutive non-demented, community-dwelling patients admitted to an acute geriatric unit. Marginal thiamine deficiency [thiamine pyrophosphate effect (TPPE) 15-24%] was present in 11 (31%) and definite thiamine deficiency (TPPE > 25%) in 6 (17%) patients. Delirium occurred in 6/19 (32%) patients with normal thiamine status and 13/17 (76%) thiamine-deficient patients (p < 0.025, chi 2 test). One or more other possible causes for delirium were present in all cases. One patient had ocular signs and a dramatic clinical response to vitamin B complex therapy. Absent ankle jerks were noted in 2/19 (10%) patients with normal thiamine status and 7/17 (41%) patients with thiamine deficiency (p = 0.06). There was no difference in anthropometric indices or in the prevalence of other nutrient deficiencies between the two groups. Thiamine deficiency is common in elderly patients admitted to hospital and may contribute to the development of delirium.

Aged↗

PubMed1988

Thiamin status of the offspring of diabetic rats.

Erythrocyte transketolase activity and thiamin pyrophosphate effect were examined in the offspring of streptozotocin-diabetic rats. Thiamin reserve was found to be significantly reduced in litters of untreated diabetic rats as compared to control and to insulin-treated diabetic rats. Supplementation of the untreated diabetic dams throughout pregnancy with oral thiamin was associated with a significantly improved thiamin status of the litters. We conclude that, due to enhanced fetal glucose turnover during diabetic gestation, a fetal thiamin deficiency state may evolve; this condition can be remedied with maternal thiamin supplementation.

Animals↗

PubMed1983

Radiometric assay for thiamine pyrophosphokinase activity in human leukocytes.

The activity of thiamine pyrophosphokinase (EC 2.7.6.2) has been demonstrated in the extract from human leukocytes using radiometric assay method. It was estimated to be 17.2 +/- 6.6 p moles of thiamine pyrophosphate formed per mg protein per hour at 37 degrees C. No thiamine pyrophosphokinase activity was detected in hemolysate of human erythrocytes under the assay condition employed.

Adenosine Triphosphate↗

PubMed2003

Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase.

Thiamin pyrophosphokinase catalyzes the pyrophosphorylation of thiamin to thiamin pyrophosphate in the presence of ATP and Mg2+. The kinetic properties of human thiamin pyrophosphokinase (hTPK1) were investigated using purified histidine-tagged recombinant protein. The plots of the initial velocity against MgATP concentrations gave a sigmoidal character when Mg2+/ATP was maintained at 1. However, the addition of an excess amount of Mg2+ resulted in the restoration of activity at lower concentrations of MgATP. A steady-state kinetics study led us to conclude that the kinase reaction obeys a ping-pong mechanism. Site-directed mutagenesis was also performed on hTPK1 to examine the contributions of eight strictly conserved residues in thiamin pyrophosphokinase on the kinetic properties. Mutations D71N, D73N, and D100N reduced kcat markedly, indicating that these aspartic acids play a crucial role in carrying out the catalytic process of hTPK1. A selective decrease in the kcat/Km(thiamin) value was observed in the D133N mutant, whereas the kcat/Km(ATP) values of T99A and R131G were significantly decreased. Interestingly, the replacement of Gln-96 with Glu caused an increase in the kcat/Km(thiamin) value (3.53-fold of the wild-type). It was therefore suggested that the residues Gln-96, Thr-99, Arg-131, and Asp-133 are conserved as functionally significant components for substrate recognition in thiamin pyrophosphokinase.

Adenosine Triphosphate↗

PubMed1991

Neonatal cardiomyopathy and lactic acidosis responsive to thiamine.

A congestive cardiomyopathy was diagnosed in a girl at the age of 4 weeks. In the weeks following she developed general muscle hypotonia and plasma lactate increased to 8.5 mmol/L. Biochemical investigations of a muscle biopsy at the age of 3 months showed a deficiency in the oxidation of all substrates tested: pyruvate plus malate, 2-ketoglutarate and palmitate plus malate. After freezing and thawing of the homogenate and the addition of essential cofactors, the oxidation of the ketoacids normalized. The oxidation defect in the untreated homogenate can be explained by a deficiency in one of the cofactors (such as thiamine pyrophosphate, NAD+ or CoASH), or by a defect in the oxidative phosphorylation. Treatment with thiamine and carnitine resulted in a decrease in blood lactate to normal levels and a dramatic clinical improvement. Suspension of thiamine caused deterioration of her clinical condition and lactic acidaemia. The thiamine therapy was then continued. The girl is now 6 years old and in perfect health.

Acidosis, Lactic↗

PubMed1999

Clinical relevance of thiamine status amongst hospitalized elderly patients.

BACKGROUND: The prevalence and the consequences of thiamine deficiency among elderly patients admitted to acute geriatric wards are not known. OBJECTIVES: (1) To assess the prevalence of thiamine deficiency in patients admitted to a geriatric ward compared to age-matched ambulatory outpatients; (2) to identify their diseases and problems associated with thiamine deficiency, and (3) to determine the relationship between the thiamine status and the cognitive and functional status of these patients. MATERIALS AND METHODS: 118 aged hospitalized patients (83 +/- 7 years; mean age +/- SD) were prospectively enrolled on admission to the geriatric ward. Their cognitive status was assessed using the Mini-Mental State Examination (MMSE) and their ability to perform their activities of daily living (ADL) using ADL scales. The effect of exogenous thiamine pyrophosphate (TPP) addition on the blood transketolase (TK) activity (TPP TK effect) served to estimate thiamine deficiency. Socioeconomic data, diseases and treatment were identified as potential associated risk factors. This group of hospitalized patients was divided according to their thiamine status to characterize the conditions associated with thiamine deficiency. Thirty-five outpatients without any functional or cognitive impairment served as a control group. RESULTS: Of 118 inpatients, 46 (39%) presented with a TPP TK effect of >15%, and 6 with values of >22%, indicating moderate and severe thiamine deficiency, respectively. Only 6 of 30 outpatients (20%) exhibited a TPP TK effect of >15% and none of them reached values of >18%. Although it tended to be lower in outpatients, the mean TPP TK effect did not statistically differ from the mean of inpatients. Thiamine-deficient inpatients comprised a larger proportion of institutionalized subjects than nondeficient inpatients (87 versus 47%, p < 0.001). Functional status, cognitive functions and the occurrence of delirium did not differ according to their thiamine status. By contrast, thiamine-deficient inpatients exhibited a higher proportion of Alzheimer's disease, depression, cardiac failure and falls. Furosemide was more frequently taken by thiamine-deficient patients. CONCLUSIONS: Severe thiamine deficiency remained quite low among the hospitalized elderly. The prevalence of moderate thiamine deficiency approached 40%. Institutionalized subjects were at particular risk of developing thiamine deficiency. Its clinical relevance on functional status and on cognitive function remained not significant. By contrast, a high proportion of falls, Alzheimer's disease, depression, cardiac failure and furosemide use could have been related to thiamine deficiency.

Activities of Daily Living↗

PubMed1984

Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal.

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.

Animals↗

PubMed1988

Thiamin absorption is not compromised in folate-deficient rats.

Thiamin absorption and excretion were assessed in rats with severe folate deficiency (FD) by determining the fate of oral 3H-labeled and intravenous 14C-labeled thiamin over a 6-h test period. Thiamin status was evaluated in these same rats by measuring transketolase activity levels of blood before (TKA) and after (TPPE) addition of thiamin pyrophosphate to the incubation mixture of the assay procedure. Two additional experiments assessed active transport of thiamin and the effect of dietary succinylsulfathiazole (SST) on TKA and TPPE in rats with moderate FD. Intestinal absorption in general and thiamin absorption in particular and thiamin status were unaltered in rats with severe FD. Inanition associated with severe FD may impair thiamin status. Thiamin absorption by active transport was not compromised in FD, and dietary succinylsulfathiazole did not affect thiamin status.

Animals↗

PubMed2002

Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study.

OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were investigated. SUBJECTS AND METHODS: Ten children were studied. Diagnosis was confirmed through the use of form E2, a computer assessed symptom score. For practical reasons, TTFD was administered twice daily for two months in the form of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses were determined through the use of the computer assessed Autism Treatment Evaluation Checklist (ATEC) forms. The erythrocyte transketolase (TKA) and thiamine pyrophosphate effect (TPPE), were measured at outset and on completion of the study to document intracellular thiamine deficiency. Urines from patients were examined at outset, after 30 days and after 60 days of treatment and the concentrations of SH-reactive metals, total protein, sulfate, sulfite, thiosulfate and thiocyanate were determined. The concentrations of metals in hair were also determined. RESULTS: At the beginning of the study thiamine deficiency was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine samples containing arsenic in greater concentration than healthy controls. Traces of mercury were seen in urines from all of these autistic children. Following administration of TTFD an increase in cadmium was seen in 2 children and in lead in one child. Nickel was increased in the urine of one patient during treatment. Sulfur metabolites in urine did not differ from those measured in healthy children. CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically. We obtained evidence of an association of this increasingly occurring disease with presence of urinary SH-reactive metals, arsenic in particular.

Arsenic↗