North-West University, Centre for Human Metabonomics, Biochemistry Department, Potchefstroom, 2520, South Africa.
Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1139-53. doi: 10.1517/17425255.2013.796929. Epub 2013 May 8.
Glycine conjugation of mitochondrial acyl-CoAs, catalyzed by glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13), is an important metabolic pathway responsible for maintaining adequate levels of free coenzyme A (CoASH). However, because of the small number of pharmaceutical drugs that are conjugated to glycine, the pathway has not yet been characterized in detail. Here, we review the causes and possible consequences of interindividual variation in the glycine conjugation pathway.
The authors review the importance of CoASH in metabolism, formation and toxicity of xenobiotic acyl-CoAs, and mechanisms for restoring levels of CoASH. They focus on GLYAT, glycine conjugation, how genetic variation in the GLYAT gene could influence glycine conjugation, and the emerging roles of glycine metabolism in cancer and musculoskeletal development.
The substrate selectivity of GLYAT and its variants needs to be further characterized, as organic acids can be toxic if the corresponding acyl-CoA is not a substrate for glycine conjugation. GLYAT activity affects mitochondrial ATP production, glycine availability, CoASH availability, and the toxicity of various organic acids. Therefore, variation in the glycine conjugation pathway could influence liver cancer, musculoskeletal development, and mitochondrial energy metabolism.
线粒体酰基辅酶 A 的甘氨酸结合反应由甘氨酸 N-酰基转移酶（GLYAT，EC 2.3.1.13）催化，是维持游离辅酶 A（CoASH）水平的重要代谢途径。然而，由于与甘氨酸结合的药物数量较少，该途径尚未得到详细描述。在这里，我们综述了个体间甘氨酸结合途径差异的原因和可能后果。
作者综述了 CoASH 在代谢、外源酰基辅酶 A 的形成和毒性以及 CoASH 水平恢复机制中的重要性。他们重点介绍了 GLYAT、甘氨酸结合、GLYAT 基因的遗传变异如何影响甘氨酸结合、以及甘氨酸代谢在癌症和肌肉骨骼发育中的新作用。
GLYAT 及其变体的底物选择性需要进一步表征，因为如果相应的酰基辅酶 A 不是甘氨酸结合的底物，有机酸可能有毒。GLYAT 活性会影响线粒体 ATP 生成、甘氨酸可用性、CoASH 可用性以及各种有机酸的毒性。因此，甘氨酸结合途径的差异可能会影响肝癌、肌肉骨骼发育和线粒体能量代谢。
