As a family of enzyme cofactors, folate is a B-vitamin carries and chemically activates one-carbon units for biosynthesis of formate, formaldehyde, and methanol. One-carbon metabolism is a metabolic network widely existing in the cytoplasm, mitochondria, and nucleus. They are the interdependent and indespensible biosynthetic pathways in these organs. One-carbon metabolism in the cytoplasm is required for polyamine synthesis and methylation reactions of a wide range of molecules such as phospholipids, neurotransmitters, proteins and numerous other small molecules. In the mitochondria, the one-carbon metabolism is also needed for a large number of reactions, such as the interconversion of serine and glycine, the metabolism of choline, purines, and histidine and the synthesis of formylated methionyl-tRNA. Besides, the one-carbon metabolism in the mitochondria provides most of the one-carbon units used for metabolism in cytoplasm. In the nucleus of certain cell types, the folate-dependent de novo thymidylate biosynthesis pathway is shown to exist, which is indicated by increasing evidence.
Because of their relations to numerous diseases and abnormal physiological conditions range from birth to senescence, there is an increasing interest in one-carbon metabolism. Though the mechanism and the responsible metabolic pathway for the initiation and progression of one-carbon metabolism remain to be determined, impairments in folate-mediated one-carbon metabolism are associated with several common diseases and developmental anomalies including vascular disease, intestinal cancers, neural tube defects and cognitive decline. It is shown that folate deficiency plays a role in the development of neural tube defects. Other birth defects and adverse pregnancy outcomes are also shown to have something to do with the folate status. Folate deficiencies are primary causes of megaloblastic anemia. At the same time, abnormal folate status and high homocysteine level are considered to be the risk factors of colorectal cancer, depression, impaired cognitive function, cardiovascular diseases and other malignancies. While in vitro experiments indicate that high homocysteine may lead to vascular lesion, some but not all studies suggest that vascular dysfunction is at least partly due to accumulation of ADMA. Likewise, in one study, supplementation with folic acid or vitamin B12 could enhance cognition in the elderly.
It is without doubt that one-carbon metabolism play a significant in physiological and pathological process. The increasing interest in one-carbon metabolism in research filed and industrial field will demand powerful profiling analytical platform enabling the simultaneous determination of multiple components of one-carbon metabolism in large-scale studies. The compounds in one-carbon metabolism are of different chemical structure, various stability and variable polarity. To measure those compounds accurately and precisely with a single method is a true challenge. However, Creative Proteomics has established sensitive, reliable, and accurate HPLC-MS/MS method for quantification of one-carbon metabolism metabolites.
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