Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Division of Innovative Diabetes Treatment, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Metabolism. 2017 May;70:51-56. doi: 10.1016/j.metabol.2017.01.031. Epub 2017 Feb 4.
The enzyme xanthine oxidoreductase (XOR) catalyzes the formation of uric acid (UA) from hypoxanthine and xanthine, which in turn are products of purine metabolism starting from ribose-5-phosphate. Besides the synthesis of UA, basic research has suggested that XOR is involved in the regulation of reactive oxygen species, adipogenesis, and peroxisome proliferator-activated receptor-γ (PPAR-γ). XOR activity has shown to be much lower in humans than in rodents, which makes its accurate measurement difficult. Recently, a novel human plasma XOR activity assay has been established using a combination of liquid chromatography (LC) and triple quadrupole mass spectrometry (TQMS) to detect [C,N]UA using [C,N]xanthine as a substrate. Using this novel assay, we for the first time determine plasma XOR activity in humans, and evaluate its association with insulin resistance, high-sensitivity C-reactive protein (hsCRP) levels, and other parameters.
Of the 29 volunteers who wished to participate in the study, 3 were excluded; of the remaining, 11 were female and 15 were male with a mean age of 25.9±3.3years. Blood samples were collected under fasting conditions in the early morning to measure XOR activity and other parameters.
The natural logarithmic value of XOR activity (ln-XOR) in plasma was 3.4±0.8pmol/h/mL. Ln-XOR had a positive correlation with UA and body mass index (BMI) and a negative correlation with quantitative insulin sensitivity check index (QUICKI) and adiponectin. In addition, ln-XOR had a positive correlation with hsCRP levels, which serves as a marker of chronic inflammation.
The present study has shown that XOR activity is correlated with serum UA levels in humans. Furthermore, even in young subjects, XOR activity is correlated with insulin resistance, BMI, and subclinical inflammation. Thus, XOR activity may be potentially involved in adiposity and subclinical inflammation in humans.
黄嘌呤氧化还原酶（XOR）催化次黄嘌呤和黄嘌呤转化为尿酸（UA），而次黄嘌呤和黄嘌呤又是从核糖-5-磷酸开始的嘌呤代谢产物。除了 UA 的合成外，基础研究还表明 XOR 参与了活性氧物质、脂肪生成和过氧化物酶体增殖物激活受体-γ（PPAR-γ）的调节。XOR 的活性在人类中比在啮齿动物中低得多，这使得其准确测量变得困难。最近，一种新的人类血浆 XOR 活性测定方法已经建立，该方法使用液相色谱（LC）和三重四极杆质谱（TQMS）相结合，使用 [C，N]黄嘌呤作为底物来检测 [C，N]UA。使用这种新的测定方法，我们首次在人类中测定了血浆 XOR 活性，并评估了其与胰岛素抵抗、高敏 C 反应蛋白（hsCRP）水平和其他参数的关系。
在 29 名希望参与研究的志愿者中，有 3 名被排除在外；在剩下的 11 名女性和 15 名男性中，平均年龄为 25.9±3.3 岁。清晨空腹采集血样，以测定 XOR 活性和其他参数。
血浆中 XOR 活性的自然对数（ln-XOR）为 3.4±0.8pmol/h/mL。ln-XOR 与 UA 和体重指数（BMI）呈正相关，与定量胰岛素敏感检查指数（QUICKI）和脂联素呈负相关。此外，ln-XOR 与 hsCRP 水平呈正相关，hsCRP 水平是慢性炎症的标志物。
本研究表明，XOR 活性与人类血清 UA 水平相关。此外，即使在年轻受试者中，XOR 活性也与胰岛素抵抗、BMI 和亚临床炎症相关。因此，XOR 活性可能与人类的肥胖和亚临床炎症有关。
