Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors

Zhao, Rongbao; Goldman, I. David

doi:10.1016/j.mam.2012.07.006

Cited by 158 publications

(157 citation statements)

References 99 publications

(140 reference statements)

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“…data in [126]). Another example here is provided by Ray and colleagues [272,273], who noted that a variety of molecules, including Janus kinase (JAK) inhibitors such as fedratinib, were transported by and/or were inhibitors of two of the three main thiamine transporters (SLC19 family [274]), thereby inducing Wernicke's encephalopathy (due to thiamine deficiency). A kind of QSAR model (in this case a pharmacophore model) suggested that 2,4-diaminopyrimidine-containing compounds can in fact adopt a conformation matching several key features of thiamine.…”

Section: Figure 5 Unsupervised and Supervised Learning Methods In Chmentioning

confidence: 99%

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Kell¹

2018

Preprint

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The yield and ease of purification of biotechnological products are typically greatly enhanced if they can be secreted into the external medium. Although not universally appreciated, however, small molecule biotechnological products do not ‘float across’ the phospholipid bilayer portion of biological membranes, and thus they need transporters to assist their passage into the extramembrane and extracellular spaces. Some of these transporters may be reversible, equilibrative transporters that might more normally be used for uptake, while others may have an efflux directionality imposed on them via suitable energy coupling mechanisms. Despite the energetic costs of small molecule synthesis, natural evolution does in fact provide a number of mechanisms by which the secretion of such products can actually enhance fitness. Where available these provide useful starting points, and assaying for such activities is crucial. In particular, in a systems biology approach, we first need to identify such/suitable activities before we can seek to increase them. They may then be improved through promoter engineering, via manipulation of control elements, or by directed evolution of the transporter proteins themselves. Modern methods of synthetic biology provide enormous opportunities for all kinds of efflux transporter engineering; they are just beginning to be realised.

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Section: Figure 5 Unsupervised and Supervised Learning Methods In Chmentioning

confidence: 99%

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Kell¹

2018

Preprint

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“…LV, into the cells (27). Below pH 7, the transport of folates by SLC19A1/RFC-1 decreases dramatically and is mainly accomplished by SLC46A1/PCFT.…”

Section: Ggh) and Folate Metabolism (Aldh1l1 Aldh1l2 Amt Atic Ftcmentioning

confidence: 96%

Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy

Odin

Sondén

Gustavsson

et al. 2015

Mol Med

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Colorectal cancer is commonly treated with 5-fluorouracil and 5-formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are dependent on expression of corresponding coding genes. To identify folate pathway genes with possible impact on leucovorin metabolism, a retrospective study was performed on 193 patients with stage III colorectal cancer. Relative expression of 22 genes putatively involved in leucovorin transport, polyglutamation and metabolism was determined in tumor and mucosa samples using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based bolus chemotherapy with leucovorin during six months, and were followed for 3 to 5 years. Cox regression analysis showed that high tumoral expression of the genes SLC46A1/PCFT (proton-coupled folate transporter) and SLC19A1/RFC-1 (reduced folate carrier 1) correlated significantly (p < 0.001 and p < 0.01, respectively) with a decreased risk of recurrent disease, measured as disease-free survival (DFS). These two genes are involved in the transport of folates into the cells and each functions optimally at a different pH. We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes. Such patients might need a more intensified therapeutic approach than those with high gene expression. Future prospective studies will determine if the expression of any of these genes can be used to predict response to leucovorin.

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“…S2B). In the same context and as the human thiamine transporter belongs to the folate transporter family (Zhao and Goldman, 2013), we also tested folate, but it did not compete for TDP transport (Supplemental Fig. S2B).…”

Section: Kinetics Of Put3-facilitated Thiamine Transportmentioning

confidence: 99%

Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines

et al. 2016

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Thiamine (vitamin B 1 ) is ubiquitous and essential for cell energy supply in all organisms as a vital metabolic cofactor, known for over a century. In plants, it is established that biosynthesis de novo is taking place predominantly in green tissues and is furthermore limited to plastids. Therefore, transport mechanisms are required to mediate the movement of this polar metabolite from source to sink tissue to activate key enzymes in cellular energy generating pathways but are currently unknown. Similar to thiamine, polyamines are an essential set of charged molecules required for diverse aspects of growth and development, the homeostasis of which necessitates long-distance transport processes that have remained elusive. Here, a yeast-based screen allowed us to identify Arabidopsis (Arabidopsis thaliana) PUT3 as a thiamine transporter. A combination of biochemical, physiological, and genetic approaches permitted us to show that PUT3 mediates phloem transport of both thiamine and polyamines. Loss of function of PUT3 demonstrated that the tissue distribution of these metabolites is altered with growth and developmental consequences. The pivotal role of PUT3 mediated thiamine and polyamine homeostasis in plants, and its importance for plant fitness is revealed through these findings.

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Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors

Cited by 158 publications

References 99 publications

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy

Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines

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