The conjugate acid of pyridine had been found to catalyze decarboxylation of alpha-mandelylthiamin (MTh). It was proposed this occurs by association between the substrate and pyridinium ion in a pi-stacked complex prior to cleavage of the C-C bond. Despite the evidence for selective acid catalyzed decarboxylation of MTh with pyridine and its derivatives, the nature of proton transfer occuring after the C-C bond breaks and before the final products form had not been investigated. General base catalyzed deprotonation of hydroxybenzylthiamin (HBnTh) has been applied as a model for the reverse reaction of acid-catalyzed decarboxylation. Kinetic analysis of this process suggests the acceleration by a preassociated pyridinium ion and the product-determining step in the decarboxylation of MTh are facilitated by independent sequential proton transfers.

The conjugate acid of pyridine had been found to catalyze decarboxylation of alpha-mandelylthiamin (MTh). It was proposed this occurs by association between the substrate and pyridinium ion in a pi-stacked complex prior to cleavage of the C-C bond. Despite the evidence for selective acid catalyzed decarboxylation of MTh with pyridine and its derivatives, the nature of proton transfer occuring after the C-C bond breaks and before the final products form had not been investigated. General base catalyzed deprotonation of hydroxybenzylthiamin (HBnTh) has been applied as a model for the reverse reaction of acid-catalyzed decarboxylation. Kinetic analysis of this process suggests the acceleration by a preassociated pyridinium ion and the product-determining step in the decarboxylation of MTh are facilitated by independent sequential proton transfers.

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Thiamin is a required coenzyme in the production of energy to fuel myocardial contraction. Therefore, thiamin deficiency (TD) may contribute to myocardial weakness by limiting the available energy for myocyte contraction. Previous studies report a wide range for the prevalence of TD in patients with heart failure (HF) (3% to 91%). These trials are limited by their small sample size, indirect measurement of thiamin status, exclusion criteria, and their focus on hospitalized patients. Therefore, this study determined the prevalence of TD in a large (n=100) group of ambulatory patients with HF, using high performance liquid chromotography. The prevalence of TD ([thiamin pyrophosphate (TPP)] ≤ 180 nM/l erythrocytes) was found to be 7%. TD was not related to furosemide use, dietary thiamin intake, severity of the HF, or age. More investigation into the factors that may influence development of TD in ambulatory patients with HF is warranted.

Thiamin is a required coenzyme in energy producing reactions that subsequently fuel myocardial contraction. Therefore, thiamin deficiency (TD) might contribute to the reduction in myocardial function observed in patients with heart failure (HF) by limiting the available energy and subsequently aggravating cardiac performance. While the prevalence of TD as well as the impact of supplementation has been examined in patients with HF, none of these studies to date has examined the impact of TD on clinical outcomes. Therefore, this study investigated the associations between erythrocyte [TPP] levels and outcomes in ambulatory patients with HF. Time-to-event probabilities were found to be not significant for acute decompensated heart failure, mortality, all-cause hospitalizations, arrhythmias, myocardial infarctions and other adverse events. Further investigations into the longer term impact of TD on outcomes and the effects of thiamin supplementation as an adjunct therapy in delaying the disease progression are needed.

Thiamin is a required coenzyme in the production of energy to fuel myocardial contraction. Therefore, thiamin deficiency (TD) may contribute to myocardial weakness by limiting the available energy for myocyte contraction. Previous studies report a wide range for the prevalence of TD in patients with heart failure (HF) (3% to 91%). These trials are limited by their small sample size, indirect measurement of thiamin status, exclusion criteria, and their focus on hospitalized patients. Therefore, this study determined the prevalence of TD in a large (n=100) group of ambulatory patients with HF, using high performance liquid chromotography. The prevalence of TD ([thiamin pyrophosphate (TPP)] ≤ 180 nM/l erythrocytes) was found to be 7%. TD was not related to furosemide use, dietary thiamin intake, severity of the HF, or age. More investigation into the factors that may influence development of TD in ambulatory patients with HF is warranted.

Thiamin is a required coenzyme in energy producing reactions that subsequently fuel myocardial contraction. Therefore, thiamin deficiency (TD) might contribute to the reduction in myocardial function observed in patients with heart failure (HF) by limiting the available energy and subsequently aggravating cardiac performance. While the prevalence of TD as well as the impact of supplementation has been examined in patients with HF, none of these studies to date has examined the impact of TD on clinical outcomes. Therefore, this study investigated the associations between erythrocyte [TPP] levels and outcomes in ambulatory patients with HF. Time-to-event probabilities were found to be not significant for acute decompensated heart failure, mortality, all-cause hospitalizations, arrhythmias, myocardial infarctions and other adverse events. Further investigations into the longer term impact of TD on outcomes and the effects of thiamin supplementation as an adjunct therapy in delaying the disease progression are needed.

La thiamine (vitamine B1) est essentielle pour toutes les formes de vie. Le diphosphate de thiamine (ThDP) est un coenzyme indispensable au métabolisme oxydatif des cellules. Dans la plupart des tissus, on trouve également le triphosphate de thiamine (ThTP), dont le rôle biologique est encore mal connu. Néanmoins, le fait quil ait été observé dans tous les organismes étudiés, depuis les bactéries jusquaux mammifères, suggère un rôle assez général comme, par exemple, une réponse à certains types de stress cellulaire (privation dacides aminés chez E. coli, flétrissement des feuilles chez A. thaliana). Lobjectif de notre travail a été de déterminer le mécanisme de synthèse du ThTP. Avant détudier son mécanisme de synthèse, nous avons étudié sa distribution dans des biopsies tissulaires et fluides corporels humains. Une telle étude systématique était intéressante car un déficit en ThTP (ou une perturbation de son métabolisme) pourrait être impliqué dans certaines pathologies, par exemple neurodégénératives ou cardiaques. Nos résultats montrent que les niveaux de diphosphate de thiamine dans les tissus humains sont relativement faibles, alors que le triphosphate de thiamine est relativement abondant. Nous avons ensuite étudié le mécanisme de synthèse du ThTP dans le cerveau de rat. Les données recueillies au cours de ces études nous ont permis de dresser plusieurs conclusions. Dans le cerveau, la synthèse du triphosphate de thiamine a lieu dans les mitochondries avec le ThDP et le phosphate inorganique (Pi) comme précurseurs. La réaction est stimulée par les substrats de la chaîne respiratoire comme le pyruvate et le succinate, et est inhibée par des agents bloquant la chaîne respiratoire, ce qui suggère que le flux délectrons à travers la chaîne respiratoire est la source dénergie pour cette réaction endergonique ThDP + Pi ↔ ThTP. La synthèse du ThTP est inhibée lorsque la Δp est dissipée par des protonophores ou par la valinomycine en présence de K+ à lextérieur. La lyse des mitochondries induit également une abolition de la formation du ThTP. La dissipation de la Δp aboutit à une hydrolyse rapide du ThTP synthétisé, suggérant que la réaction ThDP + Pi ↔ ThTP + H2O est catalysée par une ThTP synthase réversible capable de transporter des protons. Les mitochondries peuvent libérer du triphosphate de thiamine. Ce mécanisme de libération nécessite la présence de Pi et pourrait impliqué un ou plusieurs composants du pore de transition de perméabilité mitochondriale. Ainsi, la synthèse et la libération du ThTP sont soumises à des régulations spécifiques. Nos résultats montrent, pour le première fois, la production dun composé hautement énergétique, autre que lATP, par un mécanisme de couplage chimiosmotique.

Tissue thiamin diphosphate was assayed enzymatically utilizing purified brewer's yeast apotransketolase. With this assay ten uumoles of thiamin diphosphate could be detected. Total thiamin was fluorometrically measured. For one to three days rats were placed under conditions of stress, consisting of loud noise treatment, emotional stress, deprivation of paradoxical sleep, and swimming to exhaustion, respectively. The body weight was markedly decreased at the end of the respective experimental periods except with the loud noise treated group, compared with the corresponding controls. Following two to three such consecutive treatments, the adrenal weight also showed a significant increase. Thiamin diphosphate and total thiamin in liver was significantly decreased after one day's exposure to loud noise. On the other hand, thiamin diphosphate and total thiamin in brain and liver were not significantly affected by the other treatments tried in this study .

Mild thiamin deficiency is prevalent in diabetes, and high dose thiamin ameliorates some diabetic complications, but there are no definitive studies addressing thiamin intake, diabetes control and thiamin status in diabetes. Subjects were 113 people with diabetes (58 type 1, 55 type 2), 43 with and 70 without thiamin supplementation. Dietary thiamin was estimated by 24-hour recall, diabetes control by HbA1c. Age, BMI, albumin excretion, activity level and smoking status did not correlate with red cell thiamin (RCT) in either group. RCT correlated with serum thiamin (ST) (p < 0.01). In those unsupplemented, adequate dietary thiamin did not ensure normal RCT, with 15.7 % of subjects below the reference range. Supplementation to intake > 4 mg/d, was significantly associated with normal RCT (p = 0.028), with 97.7% of supplemented subjects having normal RCT. Supplementation was also significantly associated with elevated serum thiamin 24 hours post supplementation, contrary to other reports. HbA1c was not significantly associated with RCT. Conclusions: In diabetes, adequate dietary thiamin does not ensure normal red cell thiamin, but supplementation to > 4 mg/day does, raising questions about actual thiamin requirements in diabetes and supporting evidence that thiamin deficiency in diabetes is not primarily due to dietary deficiency. Diabetes control was not significantly related to thiamin status.