Over the last few years, various inborn disorders have been reported in the malate aspartate shuttle (MAS). The MAS consists of four metabolic enzymes and two transporters, one of them having two isoforms that are expressed in different tissues. Together they form a biochemical pathway that shuttles electrons from the cytosol into mitochondria, as the inner mitochondrial membrane is impermeable to the electron carrier NADH. By shuttling NADH across the mitochondrial membrane in the form of a reduced metabolite (malate), the MAS plays an important role in mitochondrial respiration. In addition, the MAS maintains the cytosolic NAD⁺/NADH redox balance, by using redox reactions for the transfer of electrons. This explains why the MAS is also important in sustaining cytosolic redox-dependent metabolic pathways, such as glycolysis and serine biosynthesis. The current review provides insights into the clinical and biochemical characteristics of MAS deficiencies. To date, five out of seven potential MAS deficiencies have been reported. Most of them present with a clinical phenotype of infantile epileptic encephalopathy. Although not specific, biochemical characteristics include high lactate, high glycerol 3-phosphate, a disturbed redox balance, TCA abnormalities, high ammonia, and low serine, which may be helpful in reaching a diagnosis in patients with an infantile epileptic encephalopathy. Current implications for treatment include a ketogenic diet, as well as serine and vitamin B6 supplementation.

中文翻译：

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苹果酸天冬氨酸穿梭的先天性疾病

在过去几年中，苹果酸天冬氨酸穿梭 (MAS) 中出现了各种先天性疾病。MAS 由四种代谢酶和两种转运蛋白组成，其中一种具有两种在不同组织中表达的亚型。它们一起形成一个生化途径，将电子从细胞质中穿梭到线粒体中，因为线粒体内膜对电子载体 NADH 是不可渗透的。通过以还原代谢物（苹果酸）的形式将 NADH 穿梭穿过线粒体膜，MAS 在线粒体呼吸中起重要作用。此外，MAS 维持细胞溶质 NAD ⁺/NADH 氧化还原平衡，通过使用氧化还原反应进行电子转移。这解释了为什么 MAS 在维持细胞溶质氧化还原依赖性代谢途径（例如糖酵解和丝氨酸生物合成）中也很重要。目前的审查提供了对 MAS 缺陷的临床和生化特征的见解。迄今为止，已报告了七分之五的潜在 MAS 缺陷。他们中的大多数呈现婴儿癫痫性脑病的临床表型。虽然不是特异性的，但生化特征包括高乳酸、高 3-磷酸甘油、氧化还原平衡紊乱、TCA 异常、高氨和低丝氨酸，这可能有助于诊断婴儿癫痫性脑病患者。目前对治疗的影响包括生酮饮食，