Aliu Ermal, Kanungo Shibani, Arnold Georgianne L
Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.
Ann Transl Med. 2018 Dec;6(24):471. doi: 10.21037/atm.2018.12.12.
Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Human utilize 21 different amino acids; most of these can be synthesized endogenously, but 9 are "essential" in that they must be ingested in the diet. In addition to their role as building blocks of protein, amino acids are key energy source (ketogenic, glucogenic or both), are building blocks of Kreb's (aka TCA) cycle intermediates and other metabolites, and recycled as needed. A metabolic defect in the metabolism of tyrosine (homogentisic acid oxidase deficiency) historically defined Archibald Garrod as key architect in linking biochemistry, genetics and medicine and creation of the term 'Inborn Error of Metabolism' (IEM). The key concept of a single gene defect leading to a single enzyme dysfunction, leading to "intoxication" with a precursor in the metabolic pathway was vital to linking genetics and metabolic disorders and developing screening and treatment approaches as described in other chapters in this issue. Amino acid disorders also led to the evolution of the field of metabolic nutrition and offending amino acid restricted formula and foods. This review will discuss the more common disorders caused by inborn errors in amino acid metabolism.
氨基酸是细胞修复、存活、再生和生长的关键组成部分及能量来源。每种氨基酸都有一个氨基、一个羧酸和一个独特的碳结构。人体利用21种不同的氨基酸；其中大多数可在体内合成，但有9种是“必需的”，即必须从饮食中摄取。除了作为蛋白质的组成部分外，氨基酸还是关键的能量来源（生酮、生糖或两者兼具），是三羧酸循环中间体和其他代谢产物的组成部分，并可根据需要循环利用。历史上，酪氨酸代谢中的一种代谢缺陷（尿黑酸氧化酶缺乏症）使阿奇博尔德·加罗德成为将生物化学、遗传学和医学联系起来并创造“先天性代谢缺陷”（IEM）一词的关键人物。单个基因缺陷导致单一酶功能障碍，进而导致代谢途径中前体“中毒”这一关键概念，对于将遗传学与代谢紊乱联系起来以及开发如本期其他章节所述的筛查和治疗方法至关重要。氨基酸紊乱还推动了代谢营养领域的发展以及含有限制性致病氨基酸的配方奶粉和食品的出现。本综述将讨论由氨基酸代谢先天性缺陷引起的更常见疾病。
