pattismith
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Can folic acid have a role in mitochondrial disorders?
Abstract
Cellular folate metabolism is highly compartmentalized, with mitochondria folate transport and metabolism being distinct from the well-known cytosolic folate metabolism. There is evidence supporting the association between low folate status and mitochondrial DNA (mtDNA) instability, and cerebral folate deficiency is relatively frequent in mitochondrial disorders. Furthermore, folinic acid supplementation has been reported to be beneficial not only in some patients with mitochondrial disease, but also in patients with relatively common diseases where folate deficiency might be an important pathophysiological factor. In this review, we focus on the evidence that supports the potential involvement of impaired folate metabolism in the pathophysiology of mitochondrial disorders.
© 2015
https://www.ncbi.nlm.nih.gov/pubmed/26183769
Folic acid could suppress Parkinson’s – new study
Posted by er134 at Jan 21, 2014
“Our data support the therapeutic potential of folic acid to enhance nucleotide pools, promoting mitochondrial biogenesis and improving mitochondrial function in neurons in neurodegenerative disease and confirm a mechanism by which this acts. Based on our findings, we propose that a high folic acid diet might be beneficial to modulate the pathogenesis of Parkinson’s disease by repressing mitochondrial dysfunction, opening a promising avenue towards exploring the role of folic acid in the prevention and therapy for neurodegenerative diseases such as Parkinson’s as well as other neurodegenerative diseases associated with defective mitochondrial function.”
http://www2.le.ac.uk/offices/press/...-could-suppress-parkinson2019s-2013-new-study
Quantitative flux analysis reveals folate-dependent NADPH production
2014
"ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway.
Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP(+) to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP(+) and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress.
Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power."
https://lsi.princeton.edu/quantitative-flux-analysis-reveals-folate-dependent-nadph-production
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