New inhibitors for dicarbonyl/L-xylulose reductase in Caenorhabditis elegans

Le Tho Son, Nguyen Hai Dang, Lai Thi Phuong, Nguyen Thi Thu, Nguyen Huy Hoang
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Abstract

Dicarbonyl/L-xylulose reductase (DCXR) is an enzyme reducing dicarbonyl (-CO-) groups in single sugar molecules and participates in the sugar metabolism of several sugar metabolism cycles in different living organisms (humans, other animals, fungi, and microorganisms). Caenorhabditis elegans, a model organism, has a unique DCXR (referred to as Ce DCXR) which plays a biochemical function similar to its homologs in the other organisms. However, the catalytic regulation of the enzyme has not been fully elucidated yet. Therefore, in this study, we investigated the chemicals which could inhibit the enzyme and found three inhibitor compounds including hexanoic acid, phosphoenolpyruvic acid, and DL-α-aminobutyrate hydrochloride for the enzyme. Because these inhibitors and their derivatives suppressed DCXRs in humans, mice, rabbits, and rats, they possibly inhibit the DCXR homologs at least in other animals. If the inhibitors and their derivatives are components in pharmaceutical products, foods, and drinks, they may come into cells, interact with DCXRs and inactivate them, causing toxicity for the host organisms.
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秀丽隐杆线虫二羰基/ l -木聚糖还原酶的新抑制剂
二羰基/ l -木糖还原酶(Dicarbonyl/L-xylulose reductase, DCXR)是一种还原单糖分子中二羰基(- co -)基团的酶,在不同的生物体(人类、其他动物、真菌和微生物)中参与几个糖代谢循环的糖代谢。秀丽隐杆线虫是一种模式生物,具有独特的DCXR(简称Ce DCXR),其生化功能与其在其他生物中的同源物相似。然而,该酶的催化调控作用尚未完全阐明。因此,在本研究中,我们对抑制该酶的化学物质进行了研究,发现了己酸、磷酸烯醇丙酮酸和DL-α-氨基丁酸盐酸盐三种抑制该酶的化合物。由于这些抑制剂及其衍生物在人、小鼠、家兔和大鼠中抑制DCXR,它们可能至少在其他动物中抑制DCXR同源物。如果抑制剂及其衍生物是药品、食品和饮料中的成分,它们可能会进入细胞,与dcxr相互作用并使其失活,从而对宿主生物造成毒性。
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