Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, PO. Box 2925 (98), Riyadh, 11461, Saudi Arabia.
Metabolomics Section, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Zahrawi Street, Al Maather, PO. Box 3354, Riyadh, 11211, Saudi Arabia.
Metabolomics. 2021 Jan 4;17(1):4. doi: 10.1007/s11306-020-01760-5.
Cystic fibrosis (CF) is a lethal multisystemic disease of a monogenic origin with numerous mutations. Functional defects in the cystic fibrosis transmembrane conductance receptor (CFTR) protein based on these mutations are categorised into distinct classes having different clinical presentations and disease severity.
The present study aimed to create a comprehensive metabolomic profile of altered metabolites in patients with CF, among different classes and in relation to lung function.
A chemical isotope labeling liquid chromatography-mass spectrometry metabolomics was used to study the serum metabolic profiles of young and adult CF (n = 39) patients and healthy controls (n = 30). Comparisons were made at three levels, CF vs. controls, among mutational classes of CF, between CF class III and IV, and correlated the lung function findings.
A distinctive metabolic profile was observed in the three analyses. 78, 20, and 13 significantly differentially dysregulated metabolites were identified in the patients with CF, among the different classes and between class III and IV, respectively. The significantly identified metabolites included amino acids, di-, and tri-peptides, glutathione, glutamine, glutamate, and arginine metabolism. The top significant metabolites include 1-Aminopropan-2-ol, ophthalmate, serotonin, cystathionine, and gamma-glutamylglutamic acid. Lung function represented by an above-average FEV1% level was associated with decreased glutamic acid and increased guanosine levels.
Metabolomic profiling identified alterations in different amino acids and dipeptides, involved in regulating glutathione metabolism. Two metabolites, 3,4-dihydroxymandelate-3-O-sulfate and 5-Aminopentanoic acid, were identified in common between the three anlayses and may represent as highly sensitive biomarkers for CF.
囊性纤维化（CF）是一种致命的多系统疾病，具有单基因起源和多种突变。基于这些突变的囊性纤维化跨膜电导调节因子（CFTR）蛋白的功能缺陷分为不同的类别，具有不同的临床表现和疾病严重程度。
本研究旨在建立 CF 患者不同类别和与肺功能相关的 CFTR 基因突变的综合代谢组学图谱。
采用化学同位素标记液相色谱-质谱代谢组学方法研究了 39 例年轻和成年 CF 患者和 30 例健康对照者的血清代谢谱。在三个水平上进行了比较，CF 与对照、CF 突变类别的比较、CF 类 III 和 IV 之间的比较，并与肺功能发现相关联。
在这三个分析中观察到了一个独特的代谢谱。在 CF 患者中，在不同类别和 III 类和 IV 类之间分别鉴定出 78、20 和 13 个显著差异失调的代谢物。鉴定出的显著代谢物包括氨基酸、二肽和三肽、谷胱甘肽、谷氨酰胺、谷氨酸和精氨酸代谢物。最显著的代谢物包括 1-氨基-2-丙醇、牛磺酸、血清素、胱硫醚和γ-谷氨酰谷氨酸。肺功能表现为平均以上的 FEV1%水平与谷氨酸水平降低和鸟苷水平升高有关。
代谢组学分析鉴定出不同氨基酸和二肽的变化，参与调节谷胱甘肽代谢。在这三个分析中，有两种代谢物，3,4-二羟基苯乙酸-3-O-硫酸盐和 5-氨基戊酸，被鉴定为共同存在，可能是 CF 的高度敏感生物标志物。
