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Cancer to Cataracts: The Mechanistic Impact of Aldo-Keto Reductases in Chronic Diseases
Anirudh P Shanbhag1,2, Purnendu Bhowmik1,3
1Bugworks Research India Pvt. Ltd., Bengaluru, Karnataka, India.
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.
Insights
Aldo-keto reductases (AKRs) are versatile enzymes involved in human metabolic pathways. Their promiscuity, while beneficial for microbial resistance, can lead to chronic diseases when exposed to synthetic compounds.
Area of Science:
- Biochemistry
- Enzymology
- Human Physiology
Background:
- Aldo-keto reductases (AKRs) are a superfamily of enzymes crucial for numerous human regulatory pathways.
- AKRs exhibit significant promiscuity, acting as a double-edged sword in biological systems.
- This enzyme superfamily is implicated in various metabolic processes and linked to chronic conditions like diabetes and cancer.
Purpose of the Study:
- To explore the dual role of aldo-keto reductases (AKRs) in human health and disease.
- To understand the implications of AKR promiscuity in the context of modern environmental exposures.
Main Methods:
- Comparative analysis of AKR functions across species.
- Review of literature on AKR involvement in metabolic pathways and disease.
- Examination of the impact of synthetic substrates on AKR activity.
Main Results:
- AKRs are widely distributed with interchangeable functions, unlike other detoxifying enzymes.
- AKR promiscuity aids in resisting pathogenic microbes.
- Exposure to synthetic molecules and processed foods can lead to "toxification" via AKRs, contributing to chronic diseases.
Conclusions:
- The inherent promiscuity of aldo-keto reductases presents both protective and detrimental effects.
- Understanding AKR activity is critical for addressing chronic diseases linked to environmental and dietary factors.
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