Biochem: Adrenal

Question 1

Describe the synthesis of the last common precursor in the pathway to all the hormones secreted by the adrenal cortex.

Answer 1

Cholesterol converted to Pregnenolone using the enzyme CYPIIA

Question 2

Name the 3 most important enzymes in the conversion of Pregnenolone to Cortisol

Answer 2

1. CYP17
2. CYP 21
3. CYP 11B1

Question 3

Describe the pathology of Apparent Mineralocorticoid Excess (AME).

Answer 3

Lack of 11beta-HSD2 enzyme in the kidney that converts cortisol to cortisone. Cortisone cannot bind the mineralocorticoid receptor.

Question 4

Name the enzymes of the cortisol-cortisone shunt.

Answer 4

Kidney: 11beta-HSD2
-converts cortisol to cortisone

Liver: 11beta-HSD1
-converts cortisone back to cortisol

Question 5

What causes the Hyperpigmentation seen in Addison Disease?

Answer 5

Lack of negative feedback of cortisol from the adrenal cortex leads to over production of ACTH. ACTH comes from a larger gene called POMC that also includes a Melanin Stimulating Hormone (MSH). MSH is also produced in excess and the body produces more melanin.

Question 6

What are the major Congenital Adrenal Hyperplasia syndromes and the affects seen?

Answer 6

Def. of 21beta-hydroxylase: inability to produce aldosterone or cortisol, leads to salt wasting, hypotension, hyperkalemia, acidosis
Overproduction of androgen leading to ambiguous genitalia

Def. of 17alpha-hydroxylase: inability to produce androgens and cortisol.

Overproduction of aldosterone: leads to symptoms similar to Conn syndrome.

Question 7

Major stimulator of aldosterone release and the signaling mechanism.

Answer 7

Angiotensin II
-IP3 calcium calmodulin pathway

(high plasma potassium also stimulates production)

Question 8

Pathway that ACTH uses to stimulate aldosterone release.

Answer 8

Gs PKA pathway

Question 9

Name the 3 major enzymes in the conversion of Pregnenolone to Aldosterone.

Answer 9

1. CYP21
2. CYP11B1
3. CYP11B2

Question 10

Name the two adrenal cortex androgens.

Answer 10

1. Dehydroepiandrosterone (DHEA)

2. Androstenedione

Question 11

Order of the synthesis of catecholamines.

Answer 11

1. Phenylalanine
2. Tyrosine
3. L-dopa
4. Dopamine
5. Norepinephrine
6. Epinephrine

Question 12

Name the 2 enzymes that degrade the catecholamines.

Answer 12

1. Monoamine Oxidase (MAO)

2. Catechol-O-methyltransferase (COMT)

Question 13

Common product of catecholamine degradation.

Answer 13

Vanillymandelic Acid (VMA)

Question 14

What condition causes raised levels of VMA in the urine?

Answer 14

Pheochromocytoma