Adrenal Hormones Flashcards
(29 cards)
P450scc
Trivial name: Cholesterol Side Chain
Cleavage
Info: First step that occurs
in mitochondria
Inhibitors: aminoglutethimide
3b-HSD
Trivial name: 3b-hydroxysteroid
dehydrogenase
Info: Intros ketone in 3
position on A ring
Inhibitors: trilostane
P450c17
Trivial name: 17a-hydroxylase; 17,20-lyase
Info: Introduces hydroxide in 17 position; cleaves stuff off if androgen is wanted
Inhibitors: ketoconazole
P450c21
Trivial name: 21-hydroxylase
Info: Introduces
hydroxide in 21 position
Inhibitors: ketoconazole
P450c11b
Trivial name: 11b-hydroxylase
Info: Introduces
hydroxide in 11b position
Inhibitors: Metyrapone;
ketoconazole
P450aldo
Trivial name: Aldosterone synthase (11band 18-hydroxylase, 18-
hydroxysteroid
dehydrogenase)
Info: One enzyme that
does 3 modifications
Inhibitors: Metyrapone;
ketoconazole
Mineralocorticoid (aldosterone) biosynthesis
Location: glomerulosa
Lacks P450c17 expression thus cannot produce glucocorticoid/androgens
Glucocorticoid (cortisol) biosynthesis
Location: fasciculata
P450c17 has impaired 17,20-lyase activity
Minor androgen synthesis
Lacks aldosterone synthase expression thus cannot
produce mineralocorticoids
Androgen pathway
Location: Reticularis
Lacks significant 21-hydroxylase expression
Lyase (Desmolase)
cleaves C-C bond in substate with formation of two pdts by a process that’s not
hydrolysis (i.e. oxidoreductase/transferase)
Hydroxylase
add/removal of -OH moiety
Hydroxysteroid dehydrogenase
ketone à alcohol (and reverse rxn)
Aminoglutethimide
How?
inhibits first step of hormone synthesis like not having a cortex
Highdose: inhibition of first step –> treatment for Cushing’s
Lowdose: inhibition of aromatase in peripheral tissues –> 3rd line BC treatment
Trilostane
How?
competitively inhibits 3b-hydroxysteroid dehydrogenase (SERM); allosteric modulator of ER
Ketoconazole
How?
Inhibits adrenal steroid enzymes P450c17 (17a-hydroxylase and 17,20-lyase) and 11b-hydroxylase
Antifungal agent –> blocks ergosterol biosynthesis in fungi
Metyrapone
How?
Inhibits 11b-hydroxylase
used for cushing’s
Mineralocorticoid Receptor Competitive Antagonist
Spironolactone–>”Potassium sparing diuretic”
Blocks aldosterone receptors
Glucocorticoid Receptor Antagonist
Mifepristone–> used for cushing’s and also considered abortion pill
Progesterone receptor antagonist
What part of the adrenocorticoid molecule is the most important for binding?
C and D rings, especially 11-18, 20, 21
How do bulky substituents on beta side of compound affect glucocorticoid and mineralocorticoid activity?
no glucocorticoid activity;
mineralocorticoid activity present
How do bulky substituents on alpha side of compound affect glucocorticoid and mineralocorticoid activity?
glucocorticoid activity present; no
mineralocorticoid activity
What are substituents that increase glucocorticoid/mineralocorticoid activity?
1-ene
9alpha-F
9alpha-Cl
What are substituents that decrease salt retention?
16alpha-OH (16alpha, 17alpha-ketal)
16 alpha or 16beta-methyl
6alpha-methyl
What are substituents that increase lipid solubility?
CHECK NOTES
