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The goal of this review article, based on a systematic literature search, is to critically assess the state of knowledge and experimental methodologies used to delineate the conversion and metabolism of the 2 methionine (Met) sources DL-methionine (DL-Met) and DL-2-hydroxy-4-(methylthio) butanoic acid (HMTBa). The difference in the chemical structures of HMTBa and DL-Met indicates that these molecules are absorbed and metabolized differently in animals. This review explores the methodologies used to describe the 2-step enzymatic conversion of the 3 enantiomers (D-HMTBa, L-HMTBa and D-Met) to L-Met, as well as the site of conversion at the organ and tissue levels. Extensive work was published documenting the conversion of HMTBa and D-Met into L-Met and, consequently, the incorporation into protein using a variety of in vitro techniques, such as tissue homogenates, cell lines, primary cell lines, and everted gut sacs of individual tissues. These studies illustrated the role of the liver, kidney, and intestine in the conversion of Met precursors into L-Met. A combination of in vivo studies using stable isotopes and infusions provided evidence of the wide conversion of HMTBa to L-Met by all tissues and how some tissues are net users of HMTBa, whereas others are net secreters of L-Met derived from HMTBa. Conversion of D-Met to L-Met in organs other than the liver and kidney is poorly documented. The methodology cited in the literature to determine conversion efficiency ranged from measurements of urinary, fecal, and respiratory excretion to plasma concentration and tissue incorporation of isotopes after intraperitoneal and oral infusions. Differences observed between these methodologies reflect differences in the metabolism of Met sources rather than differences in conversion efficiency. The factors affecting conversion efficiency are explored in this paper and are mostly associated with extreme dietary conditions, such as noncommercial crystalline diets that are very deficient in total sulfur amino acids with respect to requirements. Implications in the diversion of the 2 Met sources toward transsulfuration over transmethylation pathways are discussed. The strengths and weaknesses of some methodologies used are discussed in this review. From this review, it can be concluded that due to the inherent differences in conversion and metabolism of the 2 Met sources, the experimental methodologies (e.g., selecting different organs at different time points or using diets severely deficient in Met and cysteine) can impact the conclusions of the study and may explain the apparent divergences of conclusion found in the literature. It is recommended when conducting studies or reviewing the literature to properly select the experimental models that allow for differences in how the 2 Met precursors are converted to L-Met and metabolized by the animal to enable a proper comparison of their bioefficacy.

This literature review evaluates the absorption of methionine (Met) sources such as 2-hydroxy-4-methylthiobutyric acid (HMTBa), its calcium salts (HMTBa-Ca), and DL-methionine (DL-Met) by focusing on the state of knowledge regarding the absorption mechanism, experimental methodology, and factors affecting their absorption. The 2 Met sources differ in mechanism and site of absorption due to differences in their chemical characteristics and enzymatic conversion. This review addresses diffusion- and transport-mediated absorption systems for amino acids and carboxylic compounds, best elucidated by in vitro, ex vivo, and in vivo experimental models. Opportunities and limitations in the use of radioisotopes to depict absorption sites as well as host and microbial metabolism are described. Physiological and environmental conditions that lead to changes in gut absorptive capacity and the impact of Met source absorption are also evaluated. This review concludes that any comparison between HMTBa and DL-Met should consider their different behaviors during the absorption phase. Hence, the chemical characteristics of these 2 molecules entail different absorption sites and mechanisms, from passive absorption in the case of HMTBa and HMTBa-Ca to active transporters for DL-Met, HMTBa, and HMTBa-Ca. In addition, the different conversion modes of these 2 molecules further differentiate their absorption modes. Considering these important differences, it is easier to understand the apparent divergence between the conclusions of existing publications. When comparing these 2 molecules, it is recommended to properly adapt to the conditions under which the absorption of Met sources is evaluated.