CYP17A1

CYP17A1

Crystal structure of CYP17A1 protein.

CYP17A1 is an important enzyme involved in the biosynthesis of steroid hormones. It is a member of the cytochrome P450 superfamily of enzymes and is primarily expressed in the adrenal glands and gonads. CYP17A1 plays a crucial role in the production of both glucocorticoids and sex steroids, making it a key regulator of various physiological processes.

Structure

The CYP17A1 gene is located on chromosome 10q24.3 and consists of 8 exons. The protein encoded by this gene is composed of 508 amino acids and has a molecular weight of approximately 57 kDa. The crystal structure of CYP17A1 has been determined, revealing a heme-binding domain and a catalytic domain.

Function

CYP17A1 catalyzes two distinct reactions: 17α-hydroxylase activity and 17,20-lyase activity. In the 17α-hydroxylase reaction, CYP17A1 converts pregnenolone and progesterone into their respective 17α-hydroxylated derivatives, which are precursors for the synthesis of glucocorticoids and mineralocorticoids. In the 17,20-lyase reaction, CYP17A1 converts 17α-hydroxyprogesterone and 17α-hydroxypregnenolone into dehydroepiandrosterone (DHEA) and androstenedione, which are precursors for the synthesis of sex steroids.

Clinical Significance

Mutations in the CYP17A1 gene can lead to various disorders, including congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS). CAH is characterized by impaired cortisol synthesis and excessive androgen production, resulting in ambiguous genitalia in females and precocious puberty in both sexes. PCOS is a common endocrine disorder in women, characterized by hyperandrogenism, menstrual irregularities, and polycystic ovaries.

Role in Drug Metabolism

CYP17A1 is also involved in the metabolism of certain drugs. For example, it plays a role in the metabolism of abiraterone, a drug used in the treatment of prostate cancer. Abiraterone inhibits CYP17A1, thereby reducing the production of androgens that fuel the growth of prostate cancer cells.

See Also

• Cytochrome P450
• Steroid Hormones
• Congenital Adrenal Hyperplasia
• Polycystic Ovary Syndrome