Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 669, 69120, Heidelberg, Germany.
Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
J Inherit Metab Dis. 2018 Jan;41(1):39-47. doi: 10.1007/s10545-017-0099-2. Epub 2017 Oct 13.
Carnosinase (CN1) is a dipeptidase, encoded by the CNDP1 gene, that degrades histidine-containing dipeptides, such as carnosine, anserine and homocarnosine. Loss of CN1 function (also called carnosinase deficiency or aminoacyl-histidine dipeptidase deficiency) has been reported in a small number of patients with highly elevated blood carnosine concentrations, denoted carnosinaemia; it is unclear whether the variety of clinical symptoms in these individuals is causally related to carnosinase deficiency. Reduced CN1 function should increase serum carnosine concentrations but the genetic basis of carnosinaemia has not been formally confirmed to be due to CNDP1 mutations. A CNDP1 polymorphism associated with low CN1 activity correlates with significantly reduced risk for diabetic nephropathy, especially in women with type 2 diabetes, and may slow progression of chronic kidney disease in children with glomerulonephritis. Studies in rodents demonstrate antiproteinuric and vasculoprotective effects of carnosine, the precise molecular mechanisms, however, are still incompletely understood. Thus, carnosinemia due to CN1 deficiency may be a non-disease; in contrast, carnosine may potentially protect against long-term sequelae of reactive metabolites accumulating, e.g. in diabetes and chronic renal failure.
肉毒碱酶（CN1）是一种二肽酶，由 CNDP1 基因编码，可降解含有组氨酸的二肽，如肉碱、鹅肌肽和同型肉碱。在少数血中肉碱浓度极高的患者中报道了 CN1 功能丧失（也称为肉毒碱酶缺乏或氨基酸-组氨酸二肽酶缺乏），这些个体的各种临床症状是否与肉毒碱酶缺乏有关尚不清楚。CN1 功能降低应增加血清肉碱浓度，但肉碱血症的遗传基础尚未正式确认为 CNDP1 突变所致。与 CN1 活性降低相关的 CNDP1 多态性与糖尿病肾病的风险显著降低相关，尤其是 2 型糖尿病女性，并且可能减缓儿童肾小球肾炎慢性肾脏病的进展。啮齿动物研究表明肉碱具有抗蛋白尿和血管保护作用，但确切的分子机制仍不完全清楚。因此，由于 CN1 缺乏引起的肉碱血症可能是非疾病；相反，肉碱可能潜在地防止反应性代谢物积累的长期后果，例如在糖尿病和慢性肾衰竭中。
