Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Division of Metabolic Diseases, Heidelberg, Germany.
Clin Chim Acta. 2011 Jan 30;412(3-4):263-7. doi: 10.1016/j.cca.2010.10.016. Epub 2010 Oct 21.
We reported an association of a particular allele of the carnosinase (CNDP1 Mannheim) gene with reduced serum carnosinase (CN1) activity and absence of nephropathy in diabetic patients. Carnosine protects against the adverse effects of high glucose levels but serum carnosine concentration was generally low.
We measured the concentration of two further histidine dipeptides, anserine and homocarnosine, via HPLC. CN1 activity was measured fluorometically and for concentration we developed a capture ELISA.
We found an association between the CNDP1 Mannheim allele and reduced serum CN1 activity for all three dipeptides but no correlation to serum concentrations although anserine and homocarnosine inhibited carnosinase activity. Patients with liver cirrhosis have low CN1 activity (0.24 ± 0.17 μmol/ml/h, n=7 males; normal range: 3.2 ± 1.1, n=104; p<0.05) and CN1 concentrations (2.3 ± 1.5 μg/ml; normal range: 24.9 ± 8.9, p<0.05) but surprisingly, histidine dipeptide concentrations in serum are not increased compared to controls.
Serum histidine dipeptide concentrations are not correlated to CN1 activity. The protective effect of low CN1 activity might be related either to turnover of CN1 substrates or a protective function of dipeptides might be localized in other tissues.
我们曾报道过一种特定的肌肽酶（曼海姆）基因等位基因与糖尿病患者血清肌肽酶（CN1）活性降低和无肾病相关。肌肽可防止高血糖水平的不良影响，但血清肌肽浓度通常较低。
我们通过 HPLC 测量了两种进一步的组氨酸二肽，即肌肽和同型肌肽的浓度。通过荧光法测量 CN1 活性，并开发了一种捕获 ELISA 来测量其浓度。
我们发现，所有三种二肽的 CNDP1 曼海姆等位基因与血清 CN1 活性降低相关，但与血清浓度无相关性，尽管肌肽和同型肌肽可抑制肌肽酶活性。肝硬化患者的 CN1 活性（0.24±0.17 μmol/ml/h，n=7 名男性；正常范围：3.2±1.1，n=104；p<0.05）和 CN1 浓度（2.3±1.5 μg/ml；正常范围：24.9±8.9，p<0.05）均较低，但令人惊讶的是，与对照组相比，血清中二肽浓度并未增加。
血清组氨酸二肽浓度与 CN1 活性无关。低 CN1 活性的保护作用可能与 CN1 底物的周转率有关，或者二肽的保护作用可能定位于其他组织。
