Dipartimento di Patologia Molecolare e Terapie Innovative, sezione di Biochimica, Università Politecnica delle Marche, Via Ranieri 69, 60131 Ancona, Italy.
Blood Cells Mol Dis. 2010 Jun 15;45(1):33-9. doi: 10.1016/j.bcmd.2010.04.003. Epub 2010 May 10.
Nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the formation of nicotinamide adenine dinucleotide (NAD). In humans, three isozymes have been identified: NMNAT1, which is widely expressed in all tissues, NMNAT2 and NMNAT3, which show a tissue-specific expression and whose mRNA levels are generally lower compared to NMNAT1. In the present study we determined the individual NMNAT isozymes activity in human red blood cells (RBCs) by using a biochemical discrimination assay based on the distinctive catalytic properties of the three proteins. We found that isozyme 3 predominates over isozyme 1, whereas isozyme 2 is absent. This high prevalence of NMNAT3 is cell-aging independent and was also confirmed by analyzing the mRNA and protein levels. RBC represent the first human cell type with a remarkable predominance of NMNAT3, and this unique expression pattern is discussed in light of the catalytic properties of the isozymes and in consideration of the biochemical microenvironment of RBC.
烟酰胺单核苷酸腺苷转移酶(NMNAT)催化烟酰胺腺嘌呤二核苷酸(NAD)的形成。在人类中,已经鉴定出三种同工酶:广泛表达于所有组织中的 NMNAT1、具有组织特异性表达的 NMNAT2 和 NMNAT3,其 mRNA 水平通常低于 NMNAT1。在本研究中,我们通过使用基于三种蛋白质独特催化特性的生化区分测定法来确定人红细胞(RBC)中的个体 NMNAT 同工酶活性。我们发现同工酶 3 占优势,而同工酶 1 则不存在。这种 NMNAT3 的高流行率与细胞衰老无关,通过分析 mRNA 和蛋白质水平也得到了证实。RBC 是具有显著 NMNAT3 优势的第一种人类细胞类型,并且根据同工酶的催化特性并考虑 RBC 的生化微环境讨论了这种独特的表达模式。