Folate promotes S-adenosyl methionine reactions and the microbial methylation cycle and boosts ruminants production and reproduction

Abstract

Folate has gained significant attention due to its vital role in biological methylation and epigenetic machinery. Folate, or vitamin (B₉), is only produced through a de novo mechanism by plants and micro-organisms in the rumen of mature animals. Although limited research has been conducted on folate in ruminants, it has been noted that ruminal synthesis could not maintain folate levels in high yielding dairy animals. Folate has an essential role in one-carbon metabolism and is a strong antiproliferative agent. Folate increases DNA stability, being crucial for DNA synthesis and repair, the methylation cycle, and preventing oxidation of DNA by free radicals. Folate is also critical for cell division, metabolism of proteins, synthesis of purine and pyrimidine, and increasing the de novo delivery of methyl groups and S-adenosylmethionine. However, in ruminants, metabolism of B₁₂ and B₉ vitamins are closely connected and utilization of folate by cells is significantly affected by B₁₂ vitamin concentration. Supplementation of folate through diet, particularly in early lactation, enhanced metabolic efficiency, lactational performance, and nutritional quality of milk. Impaired absorption, oxidative degradation, or deficient supply of folate in ruminants affects DNA stability, cell division, homocysteine remethylation to methionine, de novo synthesis of S-adenosylmethionine, and increases DNA hypomethylation, uracil misincorporation into DNA, chromosomal damage, abnormal cell growth, oxidative species, premature birth, low calf weight, placental tube defects, and decreases production and reproduction of ruminant animals. However, more studies are needed to overcome these problems and reduce enormous dietary supplement waste and impaired absorption of folate in ruminants. This review was aimed to highlight the vital role of folic acid in ruminants performance.

Keywords: DNA stability; Epigenetic; Folate; Microbial methylation; Ruminants; Vitamin B12.

Fig. 1

How folate deficiency leads to genomic instability? Two way: 5,10-methylene-THF, 5,10-methylenetetrahydrofolate; 5, methyl THF, 5-methylenetetrahydrofolate; THF, tetrahydrofolate; C, cytosine; G, guanine; X denotes no capability to donate a methyl group (CH₃); TMP, thymidylate monophosphate; desoxyuridylate monophosphate, dUMP (adopted from Duthie (1999))

Fig. 2

Metabolism of folate and its relationship with methionine. The key donor (SAM) is synthesized from methionine and is used to transfer a methyl group in DNA and the protein methylation cycle. Once a methyl group is transferred, it will change into S-adenosyl homocysteine, which further becomes homocysteine, and then methionine. Methyltetrahydrofolate (THF) and vitamin B₁₂ are required as key regulatory cofactors. FAD, flavin adenine dinucleotide; NADPH, nicotinamide adenine dinucleotide phosphate