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Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets

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Abstract

Purpose

Both folate and betaine (synthesized from choline) are nutrients used to methylate homocysteine to reform the amino acid methionine following donation of its methyl group; however, it is unclear whether both remethylation pathways are of equal importance during the neonatal period when remethylation rates are high. Methionine is an indispensable amino acid that is in high demand in neonates not only for protein synthesis, but is also particularly important for transmethylation reactions, such as creatine and phosphatidylcholine synthesis. The objective of this study was to determine whether supplementation with folate, betaine, or a combination of both can equally re-synthesize methionine for protein synthesis when dietary methionine is limiting.

Methods

Piglets were fed a low methionine diet devoid of folate, choline, and betaine, and on day 6, piglets were supplemented with either folate, betaine, or folate + betaine (n = 6 per treatment) until day 10. [1-13C]-phenylalanine oxidation was measured as an indicator of methionine availability for protein synthesis both before and after 2 days of supplementation.

Results

Prior to supplementation, piglets had lower concentrations of plasma folate, betaine, and choline compared to baseline with no change in homocysteine. Post-supplementation, phenylalanine oxidation levels were 20–46 % lower with any methyl donor supplementation (P = 0.006) with no difference among different supplementation groups. Furthermore, both methyl donors led to similarly lower concentrations of homocysteine following supplementation (P < 0.05).

Conclusions

These data demonstrate an equal capacity for betaine and folate to remethylate methionine for protein synthesis, as indicated by lower phenylalanine oxidation.

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Acknowledgments

We thank M.E. Dodge for laboratory assistance. We would like to thank Dr. Simon Eaton at University College London’s Institute for Child Health for use of the isotope ratio mass spectrometer.

Financial support

This work was supported by the Canadian Institutes of Health Research (R.F.B., Grant Number 201103RNL); and the Research Development Corporation of Newfoundland and Labrador (R.F.B., Grant Number 5404-1046-104).

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Correspondence to Robert F. Bertolo.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

Authorship

L.E.M., J.L.R., R.F.B., and J.A.B. were involved in formulating the research question and designing the experiment. L.E.M. and J.L.R. carried out the experiments, and L.E.M., J.L.R., S.V.H., and E.W.R. conducted the analytical work. L.E.M., J.L.R., R.F.B., and J.A.B. analyzed and interpreted the data. L.E.M. and R.F.B. drafted the manuscript, and all authors read and reviewed the final version.

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McBreairty, L.E., Robinson, J.L., Harding, S.V. et al. Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets. Eur J Nutr 55, 2423–2430 (2016). https://doi.org/10.1007/s00394-015-1049-0

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  • DOI: https://doi.org/10.1007/s00394-015-1049-0

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