In the zona fasciculata of the adrenal cortex, which enzyme catalyzes the conversion of 11-deoxycortisol to cortisol, and what is the cofactor requirement?

Explanation

## Final Step of Cortisol Synthesis **Key Point:** **11β-hydroxylase** (also called steroid 11β-monooxygenase) catalyzes the final and rate-limiting step of cortisol synthesis: $$\text{11-deoxycortisol} \xrightarrow{11\beta\text{-hydroxylase}} \text{Cortisol}$$ ### Enzyme Characteristics - **Location:** Mitochondrial inner membrane (zona fasciculata) - **Cofactors required:** NADPH and cytochrome P450 (specifically P450c11β) - **Regulation:** Stimulated by ACTH via cAMP-PKA pathway - **Gene:** CYP11B1 (chromosome 8) ### Cortisol Synthesis Pathway ```mermaid flowchart TD A[Cholesterol]:::outcome --> B[Pregnenolone]:::outcome B --> C[17-OH Pregnenolone]:::outcome C --> D[DHEA]:::outcome D --> E[Androstenediol]:::outcome E --> F[17-OH Progesterone]:::outcome F --> G[11-Deoxycortisol]:::outcome G -->|11β-hydroxylase| H[Cortisol]:::action style H fill:#90EE90 ``` **High-Yield:** Deficiency of 11β-hydroxylase causes **congenital adrenal hyperplasia (CAH) type 1**, leading to: - Decreased cortisol and aldosterone - Accumulation of 11-deoxycortisol and precursors - Virilization in females (elevated androgens) - Hypertension (due to accumulation of 11-deoxycortisol, which has mineralocorticoid activity) **Clinical Pearl:** 11β-hydroxylase deficiency is the **second most common form of CAH** (after 21-hydroxylase deficiency), accounting for ~5–8% of CAH cases. **Mnemonic:** **"11β = Final Step"** — remember that 11β-hydroxylase adds the final hydroxyl group to complete cortisol synthesis.