Abstract
This mini-review focuses on the nutrigenomics of C-1 metabolites related to folate.
Based on the recent analytical methods, folate insufficiency among Japanese must be corrected, and international dietary allowance of 400 ㎍/day must be adopted. Folate is composed of many C-1 derivatives of folic acid (pteroyl-monoglutamate). In addition, C-1 metabolome contains choline, and so on. The development of liquid chromatography with tandem mass spectrometer (LC/MS/MS) enabled us to analyze C-1 metabolome. The low folate status results in hyperhomocysteinemia, which is an independent risk factor for cardiovascular disease, dementia, and depression. Folate supplies C-1 compounds to purine and thymidylate synthesis, DNA methylation, neurotransmitters, and homocysteine (Hcy). The concentration of unmetabolized folic acid was very low compared with that of 5-methyltetrahydrofolate because both folate and dihydrofolate reductases are driven by very high NADPH/NADP ratio supported by pentose phosphate cycle. Thus, intake of 400 μg of folic acid, which inhibits MTHFR (N5,N10 -methylenetertahydro folate reductase) in vitro, is harmless in vivo. In the TT genotype of MTHFR, harmful Hcy was increased, and serine, which is C-1 source, was lowered. In conclusion, we recommend 400μg folic acid per day for TT genotype of MTHFR, to prevent cardiovascular and psychiatric diseases.
