The compartmentation of phosphorylated thiamine derivatives in cultured neuroblastoma cells

Bettendorff, Lucien

doi:10.1016/0167-4889(94)90019-1

Cited by 46 publications

(61 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 The physiological function of ThTP and the mechanisms regulating its cellular concentration in various cell types are matters that are still largely unexplored. In rat brain and cultured neuroblastoma cells, ThTP has a high turnover, but its steady-state levels remain low (27,28). This suggests that intracellular ThTP concentration is highly regulated (29,30).…”

Section: Resultsmentioning

confidence: 92%

Molecular Characterization of a Specific Thiamine Triphosphatase Widely Expressed in Mammalian Tissues

Lakaye¹,

Makarchikov²,

Antunes³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues, and recent data suggest that it may act as a phosphate donor for the phosphorylation of some proteins. In the mammalian brain, ThTP synthesis is rapid, but its steady-state concentration remains low, presumably because of rapid hydrolysis. In this report we purified a soluble thiamine triphosphatase (ThTPase; EC 3.6.1.28) from calf brain. The bovine ThTPase is a 24-kDa monomer, hydrolyzing ThTP with virtually absolute specificity. Partial sequence data obtained from the purified bovine enzyme by tandem mass spectrometry were used to search the GenBank TM data base. A significant identity was found with only one human sequence, the hypothetical 230-amino acid protein MGC2652. The coding regions from human and bovine brain mRNA were amplified by reverse transcription-PCR, cloned in Escherichia coli, and sequenced. The human open reading frame was expressed in E. coli as a GST fusion protein. Transformed bacteria had a high isopropyl-␤-D-thiogalactopyranoside-inducible ThTPase activity. The recombinant ThTPase had properties similar to those of human brain ThTPase, and it was specific for ThTP. The mRNA was expressed in most human tissues but at relatively low levels. This is the first report of a molecular characterization of a specific ThTPase.

show abstract

Section: Resultsmentioning

confidence: 92%

Molecular Characterization of a Specific Thiamine Triphosphatase Widely Expressed in Mammalian Tissues

Lakaye¹,

Makarchikov²,

Antunes³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because in FNAD TDP levels are even lower than in Alzheimer's disease, thiamine treatment should be more effective. Thus, treatment with high doses of thiamine or one of its better-absorbed lipid-soluble derivatives such as sulbutiamine (Bettendorff et al, 1994), benfotiamine (Loew, 1996), or fursultiamine (Mimori et al, 1996) should be considered for improving the cognitive status of FNAD patients or to slow the evolution of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…As brain TDP is essentially mitochondrial (Bettendorff, 1994;Bettendorff et al, 1994), we measured the activity of citrate synthase in our samples. Citrate synthase activity was reduced by 25% in the frontal cortex of FNAD patients, suggesting a mitochondrial deficit in this region.…”

Section: Discussionmentioning

confidence: 99%

Low Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non‐Alzheimer's Type

Bettendorff

Mastrogiacomo²,

Wins

et al. 1997

Journal of Neurochemistry

View full text Add to dashboard Cite

Abstract:We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or frontotemporal dementia with five age-, postmortem delay-, and agonal status-matched control subjects. Our results reveal a 40-50% decrease in thiamine diphosphate (TDP) in the cortex of FNAD patients, whereas thiamine monophosphate was increased 49-119%. TDP synthesizing and hydrolyzing enzymes were unaffected. The activity of citrate synthase, a mitochondrial marker enzyme, was decreased in the frontal cortex of patients with FNAD, but no correlation with TDP content was found. These results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD. As TDP is an essential cofactor for oxidative metabolism and neurotransmitter synthesis, and because low thiamine status (compared with other species) is a constant feature in humans, a nearly 50% decrease in cortical TDP content may contribute significantly to the clinical symptoms observed in FNAD. This study also provides a basis for a trial of thiamine, to improve the cognitive status of the patients. Key Words: Thiamine-Thiamine diphosphate-Frontal lobe dementia-Mitochondria.

show abstract

“…Majority of thiamine in the cytoplasm (approximately 90%) is phosphorylated by TPK1 to TDP and used as a cofactor of cytosolic enzymes while the rest remains unphosphorylated [3] . Most of the TDP (approximately 90%) is transported into mitochondria via thiamine transporter from the solute carrier family of proteins encoded by the SLC25A19 gene [6] . Two mutations in the SLC25A19 cause Amish lethal microcephaly, an autosomal recessive disorder characterized by severe microcephaly, delayed brain development, α-ketoglutaric aciduria and premature death [7] .…”

Section: Overview Of Thiamine Metabolismmentioning

confidence: 99%

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

Pácal¹

2014

WJD

View full text Add to dashboard Cite

Growing prevalence of diabetes (type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro-and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine (vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency (either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics (by review of the studies mapping the prevalence and the degree of thiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given. Key words: Diabetes; Thiamine; Vitamin B1; Transketolase; Benfotiamine; Hyperglycemia; Nephropathy; Metabolic syndrome; Cardiovascular disease; Chronic kidney disease Core tip: Published data suggest deficient action of thiamine in diabetes, however, it is not currently clear by which mechanisms. Plasma levels might be decreased in diabetics (although renal function has a prevailing effect), nevertheless, intracellular concentration of thiamine diphosphate is the crucial parameter and there is not a direct relationship with the plasma thiamine since the rate of transmembrane transport (via thiamine transporters) and intracellular activation by thiamine pyrophosphokinase might affected by hyperglycemia at first place. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.

show abstract

The compartmentation of phosphorylated thiamine derivatives in cultured neuroblastoma cells

Cited by 46 publications

References 25 publications

Molecular Characterization of a Specific Thiamine Triphosphatase Widely Expressed in Mammalian Tissues

Molecular Characterization of a Specific Thiamine Triphosphatase Widely Expressed in Mammalian Tissues

Low Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non‐Alzheimer's Type

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

Contact Info

Product

Resources

About