Abstract:
Aldo-keto reductases (AKRs) are a superfamily of promiscuous enzymes that have been chiseled by evolution to act as catalysts for numerous regulatory pathways in humans. However, they have not lost their promiscuity in the process, essentially making them a double-edged sword. The superfamily is involved in multiple metabolic pathways and are linked to chronic diseases such as cataracts, diabetes, and various cancers. Unlike other detoxifying enzymes such as cytochrome P450s (CYP450s), short-chain dehydrogenases (SDRs), and medium-chain dehydrogenases (MDRs), that participate in essential pathways, AKRs are more widely distributed and have members with interchangeable functions. Moreover, their promiscuity is ubiquitous across all species and participates in the resistance of pathogenic microbes. Moreover, the introduction of synthetic substrates, such as synthetic molecules and processed foods, results in unwanted \"toxification\" due to enzyme promiscuity, leading to chronic diseases.
摘要:
Aldo-keto还原酶(AKRs)是混杂酶的超家族,已通过进化被凿成,可作为人类许多调节途径的催化剂。然而,他们并没有在这个过程中失去滥交,本质上使他们成为一把双刃剑。该超家族参与多种代谢途径,并与白内障等慢性疾病有关,糖尿病,和各种癌症。与其他解毒酶如细胞色素P450(CYP450)不同,短链脱氢酶(SDR),和中链脱氢酶(MDR),参与基本途径,AKR分布更广泛,并且具有可互换功能的成员。此外,它们的滥交在所有物种中无处不在,并参与病原微生物的抗性。此外,合成基质的引入,比如合成分子和加工食品,由于酶滥交导致不必要的“中毒”,导致慢性疾病。