Involvement of UDP-GlcNAc biosynthesis in sexual dysfunctions caused by endocrine disrupting chemicals

在人类和动物中，最近报告了男性性功能障碍。这表明，这种现象的原因被认为是内分泌干扰物对性激素受体的影响。人N-乙酰葡糖胺-1-磷酸尿苷酰转移酶（UAP 1）在睾丸和精子尾部，尤其是外层致密纤维中表达，被认为在性功能中起重要作用。在这项研究中，我们发现抗UAP 1抗体更频繁地检测到精子活动力受损的精子血浆。由于UAP 1的一级结构与几种精子表面蛋白具有部分同源性，因此抗UAP 1的抗体可阻断UAP 1及其它精子表面蛋白的功能，并导致精子多种功能的抑制。并参与真核UDP-GlcNAc生物合成，并且UAP 1已被克隆和表征。此外，对N-乙酰氨基葡萄糖（GlcNAc）的催化酶如GlcNAc激酶和GlcNAc-磷酸脱乙酰酶进行了鉴定和表征。

In human and animals, male sexual dysfunctions had been reported recently. It is suggested that the reason for this phenomenon was thought to be the effects of endocrine disrupting chemicals on sex hormone receptors. Human N-acetylglucosamine-1-phosphate uridyltransferase (UAP1) is expressed in testis and sperm tail, especially outer dense fiber and thought to play important function in sexual function. In this study, we found that the antibody against UAP1 was detected more frequently in sperm plasma with impaired sperm motility. Because the primary structure of UAP1 showed the partial homology with several sperm surface proteins, the antibody against UAP1 might prevent the function of UAP1 as well as other sperm surface proteins, and cause the inhibition of various sperm function.Furthermore, GNA1 and AGM1, which encode glucosamine-6-phosphate acetyltransferase and phosphoacetylglucosamine mutase, respectively, and are involved in eukaryotic UDP-GlcNAc biosynthesis as well as UAP1 had been cloned and characterized. Furthermore the enzymes for catabolism of N-acetylglucosamine (GlcNAc) such as GlcNAc kinase and GlcNAc-phosphate deacetylase were identified and characterized.