Insights into Interactions of Human Cytochrome P450 17A1: A Review

Himanshu      Singh; Rajnish      Kumar; Avijit      Mazumder; Salahuddin; Rupa      Mazumder; Mohd.   Mustaqeem   Abdullah
Abstract

Cytochrome P450s are a widespread and vast superfamily of hemeprotein monooxygenases that metabolize physiologically essential chemicals necessary for most species' survival, ranging from protists to plants to humans. They catalyze the synthesis of steroid hormones, cholesterol, bile acids, and arachidonate metabolites and the degradation of endogenous compounds, such as steroids, fatty acids, and other catabolizing compounds as an energy source and detoxifying xenobiotics, such as drugs, procarcinogens, and carcinogens. The human CYP17A1 is one of the cytochrome P450 genes located at the 10q chromosome. The gene expression occurs in the adrenals and gonads, with minor amounts in the brain, placenta, and heart. This P450c17 cytochrome gene is a critical steroidogenesis regulator which performs two distinct activities: 17 alpha-hydroxylase activity (converting pregnenolone to 17- hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; these precursors are further processed to provide glucocorticoids and sex hormones) and 17, 20-lyase activity (which converts 17-hydroxypregnenolone to DHEA). Dozens of mutations within CYP17A1 are found to cause 17-alpha-hydroxylase and 17, 20-lyase deficiency. This condition affects the function of certain hormone-producing glands, resulting in high blood pressure levels (hypertension), abnormal sexual development, and other deficiency diseases. This review highlights the changes in CYP17A1 associated with gene-gene interaction, drug-gene interaction, chemical-gene interaction, and its biochemical reactions; they have some insights to correlate with the fascinating functional characteristics of this human steroidogenic gene. The findings of our theoretical results will be helpful to further the design of specific inhibitors of CYP17A1.
Keywords: Cytochrome P450, CYP17A1, CYP17A1 gene-gene interactions, drug-CYP17A1 interactions, CYP17A1-chemical interactions, biochemical reactions.
Graphical Abstract

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Cite As
Current Drug Metabolism

Insights into Interactions of Human Cytochrome P450 17A1: A Review

Abstract

Graphical Abstract
