Zinc-α2-glycoprotein (ZAG) is a major plasma protein whose levels increase in chronic energy-demanding diseases and thus serves as an important clinical biomarker in the diagnosis and prognosis of the development of cachexia. Current knowledge suggests that ZAG mediates progressive weight loss through β-adrenergic signalling in adipocytes, resulting in the activation of lipolysis and fat mobilization. Here, through cross-linking experiments, amine oxidase copper-containing 3 (AOC3) is identified as a novel ZAG binding partner. AOC3-also known as vascular adhesion protein 1 (VAP-1) and semicarbazide sensitive amine oxidase (SSAO)-deaminates primary amines, thereby generating the corresponding aldehyde, H2O2 and NH3. It is an ectoenzyme largely expressed by adipocytes and induced in endothelial cells during inflammation. Extravasation of immune cells depends on amine oxidase activity and AOC3-derived H2O2 has an insulinogenic effect. The observations described here suggest that ZAG acts as an allosteric inhibitor of AOC3 and interferes with the associated pro-inflammatory and anti-lipolytic functions. Thus, inhibition of the deamination of lipolytic hormone octopamine by AOC3 represents a novel mechanism by which ZAG might stimulate lipolysis. Furthermore, experiments involving overexpression of recombinant ZAG reveal that its glycosylation is co-regulated by oxygen availability and that the pattern of glycosylation affects its inhibitory potential. The newly identified protein interaction between AOC3 and ZAG highlights a previously unknown functional relationship, which may be relevant to inflammation, energy metabolism and the development of cachexia.

中文翻译：

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锌-α2-糖蛋白作为含铜胺氧化酶 3 的抑制剂。


锌-α2-糖蛋白（ZAG）是一种主要血浆蛋白，其水平在慢性能量需求疾病中增加，因此可作为恶病质发展的诊断和预后的重要临床生物标志物。目前的知识表明，ZAG 通过脂肪细胞中的 β-肾上腺素能信号传导介导渐进性体重减轻，从而激活脂肪分解和脂肪动员。在此，通过交联实验，胺氧化酶含铜 3 (AOC3) 被鉴定为新型 ZAG 结合伴侣。 AOC3 - 也称为血管粘附蛋白 1 (VAP-1) 和氨基脲敏感胺氧化酶 (SSAO) - 使伯胺脱氨基，从而生成相应的醛、H2O2 和 NH3。它是一种主要由脂肪细胞表达并在炎症期间在内皮细胞中诱导的胞外酶。免疫细胞的外渗取决于胺氧化酶的活性，而 AOC3 衍生的 H2O2 具有胰岛素生成作用。这里描述的观察结果表明 ZAG 作为 AOC3 的变构抑制剂并干扰相关的促炎和抗脂肪分解功能。因此，AOC3 对脂肪分解激素章鱼胺脱氨基作用的抑制代表了 ZAG 可能刺激脂肪分解的新机制。此外，涉及重组 ZAG 过表达的实验表明，其糖基化受到氧可用性的共同调节，并且糖基化模式影响其抑制潜力。新发现的 AOC3 和 ZAG 之间的蛋白质相互作用凸显了一种以前未知的功能关系，这可能与炎症、能量代谢和恶病质的发展有关。