Creatine metabolism in patients with urea cycle disorders.
Creatine metabolism in patients with urea cycle disorders.
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DOI：
10.1016/j.ymgmr.2021.100791
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发表时间：
2021-12
影响因子：
1.9
通讯作者：
Longo N
中科院分区：
文献类型：
--
作者：
Ingoglia F;Chong JL;Pasquali M;Longo N
尿素循环产生精氨酸，精氨酸是肌酸生物合成的主要前体之一。在这里，我们评估了不同类型尿素循环障碍（鸟氨酸转氨基甲酰酶缺乏症（ns = 22; np = 7）、瓜氨酸血症1型（ns = 60; np = 22）、精氨酸琥珀酸尿症（ns = 81; np = 31）、精氨酸酶缺乏症（ns = 44; np = 13））患者（np = 73）血浆样本（ns = 207）中肌酸和胍丁酯（合成肌酸的前体）的水平。血浆胍乙酸酯浓度与精氨酸水平呈正相关（p < 0.001, R2 = 0.64），但与所有尿素循环缺陷患者的甘氨酸水平不相关，在大多数精氨酸酶缺乏症患者（44例中有34例）的血浆胍乙酸酯浓度高于正常水平。与胍丁酯甲基转移酶缺乏症（一种以胍丁酯浓度升高为特征的肌酸合成紊乱）患者相比，精氨酸酶缺乏症患者的肌酸水平正常（44例中32例）或高于正常（44例中12例）。肌酸水平与胍丁酯水平有显著相关性，但相关性较差（p < 0.01, R2 = 0.1），尽管在所有其他尿素循环障碍患者中肌酸水平总体处于正常范围，但在一些精氨酸琥珀酸合成酶和裂解酶缺乏症患者中肌酸水平偶尔低于正常水平。肌酸水平与蛋氨酸水平呈正相关（p < 0.001, R2 = 0.16），蛋氨酸是肌酸合成甲基的供体。尿素循环障碍患者的精氨酸水平与胍苷乙酸的直接相关性解释了精氨酸酶缺乏症中胍苷化合物浓度增加的原因。一些尿素循环缺陷患者的低肌酸水平可能是由于蛋白质摄入量低（肌酸天然存在于肉类中）和细胞内精氨酸相对或绝对缺乏所致。
The urea cycle generates arginine that is one of the major precursors for creatine biosynthesis. Here we evaluate levels of creatine and guanidinoacetate (the precursor in the synthesis of creatine) in plasma samples (ns = 207) of patients (np = 73) with different types of urea cycle disorders (ornithine transcarbamylase deficiency (ns = 22; np = 7), citrullinemia type 1 (ns = 60; np = 22), argininosuccinic aciduria (ns = 81; np = 31), arginase deficiency (ns = 44; np = 13)). The concentration of plasma guanidinoacetate positively correlated (p < 0.001, R2 = 0.64) with levels of arginine, but not with glycine in all patients with urea cycle defects, rising to levels above normal in most samples (34 out of 44) of patients with arginase deficiency. In contrast to patients with guanidinoacetate methyltransferase deficiency (a disorder of creatine synthesis characterized by elevated guanidinoacetate concentrations), creatine levels were normal (32 out of 44) or above normal (12 out of 44) in samples from patients with arginase deficiency. Creatine levels correlated significantly, but poorly (p < 0.01, R2 = 0.1) with guanidinoacetate levels and, despite being overall in the normal range in patients with all other urea cycle disorders, were occasionally below normal in some patients with argininosuccinic acid synthase and lyase deficiency. Creatine levels positively correlated with levels of methionine (p < 0.001, R2 = 0.16), the donor of the methyl group for creatine synthesis. The direct correlation of arginine levels with guanidinoacetate in patients with urea cycle disorders explains the increased concentration of guanidino compounds in arginase deficiency. Low creatine levels in some patients with other urea cycle defects might be explained by low protein intake (creatine is naturally present in meat) and relative or absolute intracellular arginine deficiency.
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影响因子：
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作者：
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影响因子：
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DOI：
10.1152/ajprenal.00356.2007
发表时间：
2007-12-01
影响因子：
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