Splicing variants of the porcine betaine–homocysteine S-methyltransferase gene: Implications for mammalian metabolism

Ganu, Radhika; Garrow, Timothy A.; Koutmos, Markos; Rund, Laurie A.; Schook, Lawrence B.

doi:10.1016/j.gene.2013.07.103

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…BHMT expression and activity in foetal livers has been reported to increase with gestational age in human [5,46] and pig studies [47] which is in line with increased BHMT activity in late pregnancy that we suggest here. Interestingly, foetal liver MTR activity decreases in the third trimester [5].…”

Section: Discussionsupporting

confidence: 90%

Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy

et al. 2016

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The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW (p < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW (p < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) (p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], (p < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], p < 0.05 to 0.20 [0.04], p < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from −0.11 [0.06], p = 0.055 to −0.23 [0.06], p < 0.001). Conclusion: During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele.

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Section: Discussionsupporting

confidence: 90%

Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy

et al. 2016

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“…In the process of betaine producing methionine, homocysteine is also a substrate for the enzyme action of BHMT. When the activity of BHMT decreases, the concentration of homocysteine in the blood rises, which has a certain relationship with vascular disease, thrombosis, and renal dysfunction 42,43 , these suggested that dietary 300 mg•kg −1 copper inhibited the methyl supply capacity of betaine and further affected protein biosynthesis of suckling piglets. These suggested that 300 mg•kg −1 copper did not support the methyl supply capacity of protein biosynthesis, which further devoid of integral health benefits for suckling piglets.…”

Section: Discussionmentioning

confidence: 99%

Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Zhang

Yao

et al. 2023

Sci Rep

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Ionomics-metabolomics association analysis is a novel method to elucidating the potential mechanisms underlying the effects of dietary copper on the overall health parameters of suckling piglets model. Few studies have elucidated the relationship between the changes of ionic and metabolic homeostasis responses to dietary copper level. The growth performance data was obtained from 180 suckling piglets which access to different copper levels: 6 (low copper diet, LC), 20 (control diet, CON), and 300 (high copper diet, HC) mg·kg−1 copper (based on diet, supplementation from CuSO4), and offered ad libitum from d 14 until weaning at 40 d of age. Dietary high level copper (300 mg·kg−1) increased the ADG and ADFI during d 14 to 28 of piglets. Six elements (Mg, Na, K, P, Cu, and Mn) concentrations significantly changes in hair among the three treatment diets. The significant increased concentrations of Na and K, and decreased concentration of Mg and Mn in 300 mg·kg−1 than 20 mg·kg−1 copper diet was observed. In current study, with the increase in copper level from 20 to 300 mg·kg−1 in diet, the correlation between hair Na, K and Cu, Mn, Zn vanish. Hair Na and K were positively correlated with serum total antioxidant capacity (T-AOC) and negatively correlated with tumor necrosis factor-α (TNF-α). The hair Cu was negatively correlated with serum malondialdehyde (MDA), total bile acid (TBA). The fecal Cu was positively correlated with serum growth hormone (GH). The results suggested that the average daily gain (ADG) in 6 mg·kg−1 copper diet and the average daily feed intake (ADFI) in 20 mg·kg−1 copper diet were decreased than 300 mg·kg−1 copper diet during d 14 to 28 and the ADG was decreased in 6 and 20 mg·kg−1 copper diets in d 29 to 40 of piglets. Dietary 20 mg·kg−1 copper maintain ion homeostasis due to increase the number of positive correlations between macroelements-microelements in hair and serum. Significantly changed Na, K, Mg, Mn and Cu concentrations in hair can reflect the adverse effects of dietary 300 mg·kg−1 copper of suckling piglets. We believe our results may benefit people to gain a better understanding of the ion interactions and metabolic homeostasis of heavy metal elements that are critical to human and animal health.

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“…In the process of betaine producing methionine, homocysteine is also a substrate for the enzyme action of BHMT. When the activity of BHMT decreases, the level of homocysteine in the blood rises, which has a certain relationship with vascular disease, thrombosis, and renal dysfunction [38,39], these suggested that 300 mg•kg -1 Cu inhibited the methyl supply capacity of betaine and further affected protein biosynthesis and the health of nursing piglets. Our previous study found that the level of pantothenic acid was decreased in the HC group [10].…”

Section: Discussionmentioning

confidence: 99%

Nursing piglet ionomics-metabolome responses to different dietary copper levels in antibiotic-free creep feed

Zhang¹,

Zheng²,

Xue³

et al. 2021

Preprint

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Background: Ionomics is a novel method to investigate the mechanism underlying the cross-talk and homeostasis of trace elements in animals. Research has not yet determined the composition and distribution of trace elements in piglets and their variations under diverse dietary high-level copper. Results: In this study, the growth performance was calculated from 180 nursing piglets which access to antibiotic-free creep feed including different copper level: 6, 20, and 300 mg·kg-1 Cu (CuSO4), and offered ad libitum from d 14 until weaning at 40 days of age. In HC (300 mg·kg-1 Cu ) group, the average daily gain (ADG) and average daily feed intake (ADFI) increased during d 14 to 28, but ADG was decreased with extension of feeding time (d 29 to 40). The ionomics profiles (hair, serum, and feces) and the correlations with serum and fecal metabolites were further analyzed. The hair Na, K, Cu, and fecal Cu concentrations were increased in HC group than other groups. The hair Na and K were negatively correlated with serum TNF-α and fecal inosine, while positively correlated with serum insulin-like growth factors-1 (IGF-1); the hair Cu was negatively correlated with serum malondialdehyde (MDA), total bile acid (TBA) and fecal putrescine, glucose-6-phosphate, fumaric acid; the fecal Cu was positively correlated with serum growth hormone, negatively correlated with fecal methionine, pantothenic acid, and uracil. Further metabolic pathway enrichment analysis showed that the hair Cu was negatively correlated with phenylalanine and tyrosine metabolism and mitochondrial electron transport chain pathways; fecal Cu was negatively correlated with betaine metabolism, and pantothenate, and CoA biosynthesis pathways. Conclusions: Dietary 300 mg·kg-1 copper promoted growth in the short term, and altered the ion balance, further affected the metabolic homeostasis, harm to the health of piglets; dietary 20 mg·kg-1 copper maintain ion homeostasis due to preservation of the interactions between macro and micro elements and suitable to meet the nutritional needs of nursing piglets. These results may benefit people to understand the molecular mechanism of ionomics effects on human and piglets’ health.

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Splicing variants of the porcine betaine–homocysteine S-methyltransferase gene: Implications for mammalian metabolism

Cited by 4 publications

References 38 publications

Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy

Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy

Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Nursing piglet ionomics-metabolome responses to different dietary copper levels in antibiotic-free creep feed

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