Cancer to Cataracts: The Mechanistic Impact of Aldo-Keto Reductases in Chronic Diseases.

IF 2.5 3区 工程技术 Q2 BIOLOGY
Yale Journal of Biology and Medicine Pub Date : 2024-06-28 eCollection Date: 2024-06-01 DOI:10.59249/VTBV6559
Anirudh P Shanbhag, Purnendu Bhowmik
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引用次数: 0

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.

从癌症到白内障:慢性疾病中醛酮还原酶的机理影响。
醛酮还原酶(AKRs)是一种超家族的杂合酶,经过进化,它们已成为人类众多调节途径的催化剂。然而,在这一过程中,它们并没有失去其杂交性,这基本上使它们成为一把双刃剑。该超家族参与多种代谢途径,与白内障、糖尿病和各种癌症等慢性疾病有关。与细胞色素 P450s(CYP450s)、短链脱氢酶(SDRs)和中链脱氢酶(MDRs)等参与基本途径的其他解毒酶不同,AKRs 的分布更为广泛,其成员的功能可以互换。此外,它们的杂交性在所有物种中无处不在,并参与了病原微生物的抗药性。此外,合成分子和加工食品等合成底物的引入也会因酶的杂交性而导致不必要的 "中毒",从而引发慢性疾病。
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来源期刊
Yale Journal of Biology and Medicine
Yale Journal of Biology and Medicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.00
自引率
0.00%
发文量
41
期刊介绍: The Yale Journal of Biology and Medicine (YJBM) is a graduate and medical student-run, peer-reviewed, open-access journal dedicated to the publication of original research articles, scientific reviews, articles on medical history, personal perspectives on medicine, policy analyses, case reports, and symposia related to biomedical matters. YJBM is published quarterly and aims to publish articles of interest to both physicians and scientists. YJBM is and has been an internationally distributed journal with a long history of landmark articles. Our contributors feature a notable list of philosophers, statesmen, scientists, and physicians, including Ernst Cassirer, Harvey Cushing, Rene Dubos, Edward Kennedy, Donald Seldin, and Jack Strominger. Our Editorial Board consists of students and faculty members from Yale School of Medicine and Yale University Graduate School of Arts & Sciences. All manuscripts submitted to YJBM are first evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field, and style. Suitable manuscripts are then subject to rigorous, fair, and rapid peer review.
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