Biosynthesis of steroid hormones Flashcards
Describe the structural characteristics of steroids.
planar, rigid, and hydrophobic..results in tight binding to receptors
The first step in synthesis of all steroid hormones is conversion of cholesterol to ________ via side chain cleavage done by ________.
pregnenolone, CYP450
The two enzymes involved in conversion of pregnenolone to DHEA (sex hormone pathway) are, in order, ________ and ________.
17-alpha hydroxylase (adds hydroxyl group to C17), then 17,20 lyase (oxidizes C17, leaving a ketone and kicking off acetyl group)
What two changes occur in the conversion of prenenolone to progesterone?
(1) oxidation of C3 hydroxyl to ketone
(2) addition so fa C4-5 double bond
Progesterone conversion to aldosterone occurs in the ______ gland and involves the enzymes _______ and _______.
adrenal, 21-hydroxylase/11-beta hydroxylase
21-hydroxylase catalyzes important reactions in the synthesis of what two steroid hormones?
aldosterone, cortisol
What are the two causes of congenital adrenal hyperplasia? Which is more common?
Major congenital adrenal hyperplasia is more common (95%) and involves deficiency in 21 hydroxylase. Minor (5%) occurs with 17-alpha hydroxylase deficiency.
Describe and explain the symptoms associated with 21-alpha hydroxylase deficiency.
(1) hypocortisolism and hypoaldosteronism - lack of critical enzyme in the synthesis of both of these hormones
(2) hypotension - low aldosterone
(3) ambiguous female genitalia/hirsutism/growth stunting - premature androgen exposure due to excess synthesis of sex hormones
Describe and explain the symptoms associated with 17-alpha hydroxylase deficiency.
(1) hypocortisolism-lack of crucial enzyme in synthesis
(2) ambiguous genitalia-lack of sex hormone synthesis
(3) hyperaldosteronism (and resulting hypertension)-excess precursor that cannot be readily converted to anything else
Outline the synthesis, including precursors and enzymes, of the sex hormones from DHEA in the ovaries and testes.
For 17-beta estradiol, aromatase is crucial for the first intermediate, and estradiol follows. DHEA is converted in one step to testosterone by 17-beta hydroxysteroid dehydrogenase. Testosterone can also be converted to estradiol.
Glucocorticoids and progesterone and transported bound to __________, while sex hormone binding globulin (SHBG) carries _______ and _______.
corticoid-binding globulin (transcortin), testosterone and estradiol
How are glucocorticoids metabolized and excreted?
metabolized in the liver (sulfation, glucuronidation, oxidation) and excreted in the bile (estrogen) or urine (cortisol, progesterone, testosterone
How does ketoconazole work? What, systemically, can it be used for?
inhibits P450scc, 17-alpha hydroxylase, 11-beta hydroxylase
