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.

这篇综述文章基于系统的文献检索，旨在批判性地评估用于描述 2 甲硫氨酸 (Met) 来源 DL-甲硫氨酸 (DL-Met) 和 DL 的转化和代谢的知识和实验方法的现状-2-羟基-4-(甲硫基)丁酸 (HMTBa)。HMTBa 和 DL-Met 的化学结构差异表明这些分子在动物体内的吸收和代谢方式不同。本综述探讨了用于描述 3 种对映体（D-HMTBa、L-HMTBa 和 D-Met）到 L-Met 的两步酶促转化的方法，以及器官和组织水平的转化位点。发表了大量工作，记录了 HMTBa 和 D-Met 转化为 L-Met，并因此使用各种体外技术将其掺入蛋白质中，例如组织匀浆、细胞系、原代细胞系和单个组织的外翻肠囊。这些研究说明了肝脏、肾脏和肠道在 Met 前体转化为 L-Met 中的作用。使用稳定同位素和输注的体内研究组合提供了所有组织将 HMTBa 广泛转化为 L-Met 的证据，以及一些组织如何成为 HMTBa 的净使用者，而其他组织是源自 HMTBa 的 L-Met 的净分泌者。在肝脏和肾脏以外的器官中 D-Met 向 L-Met 的转化记录很少。文献中引用的确定转化效率的方法范围从测量尿液、粪便和呼吸排泄到血浆浓度和腹膜内和口服输注后同位素的组织掺入。这些方法之间观察到的差异反映了 Met 源代谢的差异，而不是转化效率的差异。本文探讨了影响转化效率的因素，这些因素大多与极端饮食条件有关，例如非商业结晶饮食，其总硫氨基酸相对于需求而言非常缺乏。讨论了将 2 Met 源转向转甲基化途径转硫作用的意义。本综述讨论了所用某些方法的优点和缺点。从这篇综述中可以得出结论，由于 2 Met 来源在转化和代谢方面的内在差异，实验方法（例如，在不同的时间点选择不同的器官或使用严重缺乏 Met 和半胱氨酸的饮食）会影响研究的结论，并可能解释文献中结论的明显差异。建议在进行研究或查阅文献时正确选择实验模型，以允许 2 Met 前体如何转化为 L-Met 并被动物代谢，从而能够正确比较它们的生物功效。