• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5333-5338
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• 2012

Vitamin B6 functions as a coenzyme in >140 enzymatic reactions involved in the metabolism of amino acids, carbohydrates, neurotransmitters, and lipids. It comprises a group of three related 3-hydroxy-2-methyl-pyrimidine derivatives: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their phosphorylated derivatives [pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP)], In the folate metabolism pathway, PLP is a cofactor for the mitochondrial and cytoplasmic isozymes of serine hydroxymethyltransferase (SHMT2 and SHMT1), the P-protein of the glycine cleavage system, cystathionine ${\beta}$-synthase (CBS) and ${\gamma}$-cystathionase, and betaine hydroxymethyltransferase (BHMT), all of which contribute to homocysteine metabolism either through folate-mediated one-carbon metabolism or the transsulfuration pathway. Folate cofactors carry and chemically activate single carbons for the synthesis of purines, thymidylate and methionine. So the evidence indicates that vitamin B6 plays an important role in maintenance of the genome, epigenetic stability and homocysteine metabolism. This article focuses on studies of strand breaks, micronuclei, or chromosomal aberrations regarding protective effects of vitamin B6, and probes whether it is folate-mediated one-carbon metabolism or the transsulfuration pathway for vitamin B6 which plays critical roles in prevention of cancer and cardiovascular disease.

• Journal of Animal Science and Technology
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• v.64 no.3
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• pp.481-499
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• 2022

This study aims to determine the effects of D-methionine (D-Met) isomer and the methionine precursor 2-hydroxy-4-methylthiobutanoic acid i (HMBi) supplementation on milk protein synthesis on immortalized bovine mammary epithelial cell (MAC-T). MAC-T cells were seeded using 10-cm dishes and cultured in Dulbecco's modified Eagle's medium/F12 (DMEM/F12) basic medium. The basic medium of DMEM/F12 was replaced with the lactogenic DMEM/ F12 differentiation medium when 90% of MAC-T cells reached confluency. The best dosage at 0.6 mM of D-Met and HMBi and incubation time at 72 h were used uniformly for all treatments. Each treatment was replicated six times wherein treatments were randomly assigned in a 6-well plate. Cell, medium, and total protein were determined using a bicinchoninic acid protein assay kit. Genes, proteomics and metabolomics analyses were also done to determine the mechanism of the milk protein synthesis pathway. Data were analyzed by two-way analysis of variance (ANOVA) with supplement type and plate as fixed effects. The least significant difference test was used to evaluate the differences among treatments. The HMBi treatment group had the highest beta-casein and S6 kinase beta-1 (S6K1) mRNA gene expression levels. HMBi and D-Met treatments have higher gene expressions compared to the control group. In terms of medium protein content, HMBi had a higher medium protein quantity than the control although not significantly different from the D-Met group. HMBi supplementation stimulated the production of eukaryotic translation initiation factor 3 subunit protein essential for protein translation initiation resulting in higher medium protein synthesis in the HMBi group than in the control group. The protein pathway analysis results showed that the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, phosphoinositide 3 kinase, and pyruvate metabolism. The HMBi group stimulated the pentose phosphate and glycolysis pathways. Metabolite analysis revealed that the D-Met treatment group increased seven metabolites and decreased uridine monophosphate (UMP) production. HMBi supplementation increased the production of three metabolites and decreased UMP and N-acetyl-L-glutamate production. Taken together, D-Met and HMBi supplementation are effective in stimulating milk protein synthesis in MAC-T cells by genes, proteins, and metabolites stimulation linked to milk protein synthesis.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.5
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• pp.689-694
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• 2016

The objective of the current study was to evaluate the effect of supplementation of either L-methionine (L-Met) or DL-methionine (DL-Met) to diets of starter pigs on nitrogen (N) balance, metabolism, and serum amino acid profile. Eighteen crossbred ($Duroc{\times}Landrace{\times}Yorkshire$) barrows weighing $15.45{\pm}0.88kg$ were randomly allotted to 1 of 3 diets with 6 pigs per treatment. The diets included a basal diet (Met-deficient diet) containing 0.24% standardized ileal digestibility Met with all other essential nutrients meeting the pig's requirements. The other two diets were produced by supplementing the basal diet with 0.12% DL-Met or L-Met. The experiment lasted for 18 days, consisting of a 13-day adaptation period to the diets followed by a 5-day experimental period. Pigs were fed ad libitum and free access to water throughout the experiment. Results showed that the supplementation of either L-Met or DL-Met improved N retention, and serum methionine concentration, and decreased N excretion compared with basal diet (p<0.01). The N retention of pigs fed diets supplemented with the same inclusion levels of DL-Met or L-Met were not different (p>0.05). In conclusion, on equimolar basis DL-Met and L-Met are equally bioavailable as Met sources for starter pigs.

• Food Science of Animal Resources
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• v.34 no.1
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• pp.65-72
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• 2014

This study is executed to develop probiotics which produce S-adenosyl-L-methionine (SAM), a methyl group donor of the 5-methyltetrahydrofolate methylation reaction within the animal cell. SAM is an essential substance for the synthesis, activation, and metabolism of hormones, neurotransmitters, nucleic acids, phospholipids, and cell membranes of animals. The SAM is also known as a nutritional supplement to improve brain functions of the human. In this study, the SAM-producing strains are identified in 18 types of salted fish, and then, the strains with excellent SAM productions are being identified, with 1 strain in the Enterococcus genus and 9 strains in the Bacillus genus. Strains with a large amount of SAM production include the lactic acid bacteria such as En. faecium and En. durans, En. sanguinicola, as well as various strains in the Bacillus genus. The SAM-overproducing strains show antibacterial activities with certain harmful microbes in addition to the weak acid resistances and strong bile resistances, indicating characteristics of probiotics. It is possible that the jeotgal-originated beneficial strains with overproducing SAM can be commercially utilized in order to manufacture SAM enriched foods.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.301-304
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• 2005

S-Adenosyl-L-Methionine(SAM) has an important role for DNA methylation and cell signaling. SAM was synthesized from methionine and ATP by SAM synthetase and play an pivotal function in the primary and secondary metabolism of cells. Recent studies have revealed in the effect of SAM in case of morphological differentiation in both eukaryotes and prokaryotes. We isolated SAM gene from Saccharomyces cerevisiae and cloned it into expression vector for E. coli respectively. An 1.15 kb SAM-s gene fragment was isolated by Low-strigency PCR using ORF primer. By the analysed primary sequence deduced from DNA sequence, this gene included conserved domains similar with other well-known SAM synthetase. First of all, SAM synthetase gene cloned pGEM-T vector and subcloned into histidine tagging system to purify the expressed protein using metal chelating resin. Typical characteristic analysis of this enzyme is underway.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.597-615
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• 2023

Healthy aging can be defined as an extended lifespan and health span. Nutrition has been regarded as an important factor in healthy aging, because nutrients, bioactive food components, and diets have demonstrated beneficial effects on aging hallmarks such as oxidative stress, mitochondrial function, apoptosis and autophagy, genomic stability, and immune function. Nutrition also plays a role in epigenetic regulation of gene expression, and DNA methylation is the most extensively investigated epigenetic phenomenon in aging. Interestingly, age-associated DNA methylation can be modulated by one-carbon metabolism or inhibition of DNA methyltransferases. One-carbon metabolism ultimately controls the balance between the universal methyl donor S-adenosylmethionine and the methyltransferase inhibitor S-adenosylhomocysteine. Water-soluble B-vitamins such as folate, vitamin B6, and vitamin B12 serve as coenzymes for multiple steps in one-carbon metabolism, whereas methionine, choline, betaine, and serine act as methyl donors. Thus, these one-carbon nutrients can modify age-associated DNA methylation and subsequently alter the age-associated physiologic and pathologic processes. We cannot elude aging per se but we may at least change age-associated DNA methylation, which could mitigate age-associated diseases and disorders.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6249-6256
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• 2013

One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin $B_6$ intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin $B_2$, vitamin $B_6$, and vitamin $B_{12}$ with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin $B_{12}$ intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin $B_6$. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.10
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• pp.1393-1398
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• 2011

Four 4-month old Charolais${\times}$Dorset male sheep (initial liveweight $25.0{\pm}1.1\;kg$), fitted with rumen and abomasal fistulas and nourished by total intragastric infusions, were used to study the relationships between methionine (Met) supply, nitrogen (N) retention and plasma insulin-like growth factor-I (IGF-I). Four graded levels of Met, i.e. 0 g/16 g N, 1.76 g/16 g N, 3.52 g/16 g N and 7.04 g/16 g N, were infused into abomasums as experimental treatments. The sheep and treatments were allocated in a $4{\times}3$ incomplete Latin square design (Yudon square design). The experiment lasted 3 periods and each period was 10 days. Quadratic correlations were found between Met level (x, g/16 g N) and N retention (y, g/d): y = $-0.03x^2$+0.41x+2.62, $r^2$ = 0.66, n = 12, p = 0.008, and between methionine level (x, g/16 g N) and plasma IGF-I concentration (y, ng/ml): y = $0.80x^2$-4.53x+190.24, $r^2$ = 0.51, n = 12, p = 0.009. No significant correlation was found between plasma IGF-I (x, ng/ml) and N retention (y, g/d) (p>0.05). It was concluded that Met level had a significant influence on N retention and plasma IGF-I concentration whereas IGF-I might not be an important mediator in the regulation of N metabolism by Met in growing sheep nourished by total intragastric infusions.

• Journal of Ginseng Research
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• v.22 no.4
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• pp.316-323
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• 1998

To study e(feces of Korean Binseng (Parfax ginseff C. A. hfeyer) total saponin fraction on spermidine and spermine metabolism in rat reproductive systems, we administrated the saponin fractation to rats for 2 years. Then, we determined the activities of S-adenosylmethionine decarboxylase (SAMDC), the quantitation of the enzyme protein and the amounts of spermidine and spermine contents In prostate and testis. In young sexually immature stage, administration of Korean ginseng saponin fraction showed no effect on SAMDC activities. The stimulatory effect on the activities of SAMDC gradually increased and reached maximal activities in test groups of prostate and testis at sexually mature stage. The amounts of SAMDC protein in test groups were paralleled by the changes of SAMDC activities in test groups, indicating that all of the increased activity occurring in administration of ginseng saponin fraction was not due to the activation of SAMDC activity but to the Increase in enzyme protein. However, the spermidine and spermine contents of test groups showed small increase in compared to that of control groups. From these results, we suggest that administration of ginseng saponin fraction alter the spermidine and spermine metabolism in sexually mature and aged reproductive systems in rats.

• YAKHAK HOEJI
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• v.53 no.2
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• pp.69-73
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• 2009

Acute betaine treatment induces time-dependent changes in the hepatic glutathione (GSH), cysteine and S-adenosylmethionine (SAM) levels. Our previous study demonstrated that betaine administered $1{\sim}4$ hours prior to sacrifice decreased hepatic GSH levels, but these levels were increased when measured 24 hours following the treatment. The present study was aimed to determine dose-dependent effects of betaine on hepatic metabolism of sulfur amino acid in mice. Mice were sacrificed 2.5 or 24 hours after intraperitoneal treatment with betaine at different dose levels ranging from 50 to 1000 mg/kg. The concentrations of methionine and SAM were increased by a betaine dose of 100 mg/kg, and the concentrations of GSH and cysteine were decreased by a betaine dose of 200 mg/kg at 2.5 hours. These changes were augmented with increasing doses of betaine. At 24 hours following betaine treatment, increased GSH and decreased taurine levels were observed from dose levels of 400 mg/kg. Changes in hepatic activities of cystathionine beta-synthase, gammaglutamylcysteine ligase and cysteine dioxygenase were observed from dose levels of $200{\sim}400$ mg/kg of betaine administered 24 hours prior to sacrifice.