– Aldo-keto reductases comprise of AKR1C1-AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. there is a strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Type I human hepatic 3alpha-hydroxysteroid dehydrogenase (AKR1C4) plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism.