Question 1

What is the Meaning of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

11β-Hydroxysteroid Dehydrogenase Type 2, commonly known as 11β-HSD2, is an essential enzyme responsible for the metabolic inactivation of active glucocorticoids, such as cortisol, into their inert 11-keto forms, like cortisone. This enzymatic conversion serves a critical protective role, preventing cortisol from inappropriately activating the mineralocorticoid receptors, which are primarily designed to respond to aldosterone.

Question 2

What is the Context of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

This enzyme is predominantly located in specific tissues that are highly sensitive to mineralocorticoids, including the renal collecting ducts, colon, salivary glands, and the placenta. In these sites, 11β-HSD2 acts as a local barrier, ensuring that the mineralocorticoid receptor remains selectively responsive to aldosterone, despite circulating cortisol levels being significantly higher. Its presence is fundamental for maintaining the integrity of mineralocorticoid signaling pathways.

Question 3

What is the Significance of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

The proper function of 11β-HSD2 is of considerable clinical significance for maintaining normal blood pressure and electrolyte balance. When this enzyme's activity is compromised, cortisol gains unhindered access to mineralocorticoid receptors, leading to a condition that mimics excessive aldosterone activity. This can manifest as severe hypertension, low potassium levels (hypokalemia), and metabolic alkalosis, a constellation of symptoms termed apparent mineralocorticoid excess (AME) syndrome.

Question 4

What is the Mechanism of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

11β-HSD2 catalyzes a unidirectional reaction where it oxidizes the 11β-hydroxyl group of cortisol, converting it into the 11-ketosteroid cortisone, utilizing NAD+ as a cofactor. This biochemical transformation renders cortisol unable to bind effectively to the mineralocorticoid receptor. By locally metabolizing cortisol into an inactive form, the enzyme effectively reduces the concentration of active glucocorticoid at the receptor site, thereby allowing aldosterone to selectively exert its precise physiological effects on sodium and potassium transport.

Question 5

What is the Application of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

Clinically, understanding 11β-HSD2 is crucial in the diagnostic evaluation of patients presenting with unexplained hypertension and hypokalemia. Conditions such as congenital apparent mineralocorticoid excess syndrome, which stems from genetic mutations in the HSD11B2 gene, directly result from impaired enzyme function. Furthermore, the consumption of licorice, containing glycyrrhizic acid, can inhibit 11β-HSD2, inducing a phenocopy of mineralocorticoid excess. Awareness of these interactions guides precise diagnostic and therapeutic approaches in clinical practice.

Question 6

What is the Metric of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

The functional status of 11β-HSD2 can be assessed through specific biochemical measurements, most notably by determining the ratio of urinary free cortisol to urinary free cortisone (UFC/UFE) or the plasma cortisol to cortisone ratio. An elevated ratio strongly suggests reduced 11β-HSD2 activity, indicating impaired cortisol inactivation. Genetic sequencing of the HSD11B2 gene can provide a definitive diagnosis for inherited forms of enzyme deficiency, complementing biochemical findings.

Question 7

What is the Risk of 11β-Hydroxysteroid Dehydrogenase Type 2?

Accepted Answer

Dysfunction or inhibition of 11β-HSD2 carries substantial clinical risks, primarily presenting as severe hypertension, hypokalemia, and metabolic alkalosis. These adverse outcomes result from the uncontrolled activation of mineralocorticoid receptors by cortisol, leading to excessive sodium retention and potassium excretion. Individuals with inherited defects in the HSD11B2 gene are predisposed to early-onset and often severe forms of hypertension. Moreover, substances like glycyrrhizic acid found in licorice can acutely induce these risks by inhibiting the enzyme's critical function.

11β-Hydroxysteroid Dehydrogenase Type 2

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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