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Thiamine Pyrophosphate (thiamine + pyrophosphate)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

Temporal changes in Sander vitreus egg thiamine levels

JOURNAL OF FISH BIOLOGY, Issue 4 2005
M. E. Barnes
Thiamine pyrophosphate was the predominant form of thiamine present initially in walleye Sander vitreus eggs from two spawning locations in Lake Oahe, South Dakota, U.S.A. Total thiamine content in the eggs at fertilization was 5·18 and 7·97 nmol g,1 for eggs from the Moreau and Grand River spawning sites respectively, and egg thiamine content in all its forms dropped dramatically at the next sampling period of 48 temperature units (TU). Thiamine values did not significantly drop after the 48 TU period, but mean total thiamine composition was < 0·9 nmol g,1 at the last sampling date (156 TU) just prior to hatching. [source]

The effect of thiamine supplementation on tumour proliferation

FEBS JOURNAL, Issue 15 2001
A metabolic control analysis study
Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, ,,2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study. [source]

Site-specific contribution of proton-coupled folate transporter/haem carrier protein 1 in the intestinal absorption of methotrexate in rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2009
Tomoharu Yokooji
Abstract Objectives Methotrexate is reportedly a substrate for proton-coupled folate transporter/haem carrier protein 1 (PCFT/HCP1) and reduced folate carrier 1 (RFC1). In this study, we examined the contribution of PCFT/HCP1 and RFC1 in the intestinal absorption of methotrexate in rats. Methods Western blot analysis was carried out to evaluate the protein levels of PCFT/HCP1 and multidrug resistance-associated protein 2 in brush-border membrane of rat small intestine. Mucosal uptake of methotrexate was studied in the rat everted small intestine and an in-situ intestinal perfusion study of methotrexate was also carried out in rats. Key findings In transport studies using everted intestine, the mucosal methotrexate influx rate in proximal intestine at pH 5.5 was significantly greater than that at pH 7.4. Coadministration of folate or its analogues, such as folinate and 5-methyltetrahydrofolate, substrates for both PCFT/HCP1 and RFC1, significantly suppressed the methotrexate influx at pH 5.5, whereas thiamine pyrophosphate, an inhibitor for RFC1 alone, exerted no significant effect. Western blot analysis showed higher PCFT/HCP1 expression in proximal than distal small intestine. In distal small intestine, methotrexate influx rate was low and was not pH dependent. Also, folate and its analogues exerted no significant effect on methotrexate absorption. Conclusions Based on the present and our previous results, the site-specific contributions of various transporters including PCFT/HCP1 in methotrexate intestinal absorption were discussed. The variation in luminal pH and the involvement of multiple transporters in methotrexate absorption may cause variation in oral bioavailability among patients. [source]

Mechanism-Guided Library Design and Dual Genetic Selection of Synthetic OFF Riboswitches

CHEMBIOCHEM, Issue 14 2009
Norihito Muranaka Dr.
Abstract After the recent discovery of bacterial riboswitches, synthetic riboswitches have been engineered by using natural and artificial RNA aptamers. In contrast to natural riboswitches, the majority of synthetic riboswitches in bacteria reported to date are ON switches that activate gene expression in response to the aptamer ligand. In this study, we adopted a mechanism-guided approach to design libraries predisposed to contain OFF riboswitches that respond to thiamine pyrophosphate (TPP). The first library design exploited a pseudo-Shine-Dalgarno (SD) sequence located near the 3,-end of the TPP aptamer, which would be less accessible to the ribosome when the aptamer is bound to TPP. In the second library, an SD sequence was strategically placed in the aptamer's P1 stem, which is stabilized upon ligand binding. OFF riboswitches were obtained by dual genetic selection of these libraries. The results underscore the importance of effective library design to achieve desired riboswitch functions. [source]