Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period.
Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period.
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DOI：
10.1007/8904_2018_99
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Honda, Akira
中科院分区：
文献类型：
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作者：
Miyazaki, Teruo;Nagasaka, Hironori;Honda, Akira
背景：Citrin（线粒体天冬氨酸-谷氨酸转运蛋白）缺乏会导致碳水化合物能量代谢和尿素循环失败，以及新生儿（NICCD）和成人（CTLN2）阶段几种氨基酸血清水平的变化。然而，NICCD和CTLN2之间的临床表现是解决的，但原因仍不清楚。本研究评估了健康阶段citrin缺乏儿童的血清氨基酸谱。方法：采用HPLC-MS/MS分析，对20名肝功能正常的5-13岁citrin缺乏儿童和35名年龄匹配的健康对照者的血清氨基酸进行了评估。结果：在citrin缺乏儿童中未观察到NICCD和CTLN2阶段特征的血清氨基酸变化。参与尿素循环的氨基酸，包括精氨酸、鸟氨酸、瓜氨酸和天冬氨酸，在柠檬酸缺乏儿童中与各自的对照水平相当，但血清尿素含量高出两倍，表明尿素循环功能正常。与对照组相比，缺乏柠檬酸的儿童的血糖水平正常，但生糖氨基酸和谷氨酰胺显着降低。此外，在citrin缺乏儿童中，生酮氨基酸、支链氨基酸（BCAAs）、缬氨酸中间体3-羟基异丁酸和β-丙氨酸也显着增加。结论：citrin缺乏儿童在健康阶段的血清氨基酸谱表现出与NICCD和CTLN2阶段不同的特征，提示尿素循环功能和能量代谢的失败可能通过以下途径得到补偿：摘要：与同龄健康对照儿童相比，健康期Citrin缺乏儿童的血清氨基酸特征，包括生糖氨基酸减少，生酮氨基酸、支链氨基酸、缬氨酸中间体和β-丙氨酸增加，提示血清氨基酸的特征性改变可能是由于能量代谢和氨解毒的代偿所致。
BACKGROUND: Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage.METHODS: Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls.RESULTS: The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and beta-alanine were also found in the citrin-deficient children.CONCLUSION: The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism.SYNOPSIS: In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and beta-alanine, were found by comparison to the age-matched healthy control children, and it suggested that the characteristic alteration of serum amino acids may be resulted from compensation for energy metabolism and ammonia detoxification.