Adrenal Hormones Flashcards
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
