17,20-lyase

17,20-Lyase

17,20-Lyase is an important enzyme in the biosynthesis of steroid hormones. It is responsible for the conversion of 17α-hydroxyprogesterone to androstenedione and 17α-hydroxypregnenolone to dehydroepiandrosterone (DHEA). This enzyme is a part of the cytochrome P450 family, specifically known as CYP17A1.

Function

17,20-Lyase activity is crucial in the production of androgens and estrogens, which are vital for sexual development and reproductive function. The enzyme catalyzes the cleavage of the C17-C20 bond in steroid precursors, a key step in the production of sex steroids. This reaction occurs in the adrenal glands and gonads.

Mechanism

The enzyme 17,20-Lyase functions by utilizing a heme iron group to facilitate the cleavage of the carbon-carbon bond. It requires molecular oxygen and NADPH as cofactors. The enzyme's activity is regulated by cytochrome b5, which enhances its lyase activity.

Clinical Significance

Deficiencies in 17,20-Lyase activity can lead to disorders of sexual development and adrenal function. For example, a deficiency can result in congenital adrenal hyperplasia, a condition characterized by impaired steroidogenesis leading to ambiguous genitalia and adrenal insufficiency.

Inhibitors of 17,20-Lyase, such as abiraterone, are used in the treatment of prostate cancer by reducing androgen production.

Genetic Aspects

The gene encoding 17,20-Lyase, CYP17A1, is located on chromosome 10q24.3. Mutations in this gene can lead to enzyme deficiencies and associated clinical syndromes.

Also see

• Steroidogenesis
• Cytochrome P450
• Androgen
• Estrogen
• Congenital adrenal hyperplasia