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stereochemistry differences at these points can make significant changes in biological activity |
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Definition
if the bond is projecting into the plane of the paper, it is designated ( )
if the bond is projecting out of the plane of the paper, it is designated ( ) |
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numbering of 5-alpha-cholestane
C-27 steroid with no double bonds |
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the name of this C-18 steroid |
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the name of this C-19 steroid |
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the name of this C-21 steroid |
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Term
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enzyme catalyzed cleavage of the side chain of cholesterol and the conversion to the C-21 steroid pregnenolone
pregnenolone serves as the precursor of the adrenocorticoids |
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Definition
| conversion of cholesterol to pregnenolone |
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Definition
conversion of pregnenolone to cortisol (glucocorticoid)
reaction occurs in the endoplasmic reticulum |
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| conversion of pregnenolone to aldosterone |
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Term
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summary:
1) oxidation of hydrocortisone to cortisone at the 11 position leads to a biologically active compound (but less active than hydrocortisone)
2) action on hydrocortisone by 5beta-reductase leads to an inactive metabolite
3) the 3-keto group of 5beta-dihydrocortisol can be reduced by 3alpha-hydroxysteroid dehydrogenase. This is a reversible reaction and both metabolites are biologically active |
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Definition
| metabolism of hydrocortisone |
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Term
1) reduction of the 4,5 double bond to the 5alpha and 5beta dihydrosteroids. This leads to a loss of biological activity.
2) reduction of the 3-keto function to either 3alpha or 3beta. this leads to loss of biological function
3) in some cases (cortisone, hydrocortisone), the 11-keto-11beta-OH are metabolically interconvertible
other routes of metabolism include:
6 beta hydroxylase (CYP3A4)
reduction of the C-20 C=O group to 20-OH analogues |
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Definition
| in general, the main routes of metabolites of the glucocorticoids are |
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Term
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all estrogens have an aromatic ring |
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Definition
| conversion of androstenedione to estrone |
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Term
hydrocortisone
11beta-OH
21-OH
17alpha-OH
3-C=O |
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testosterone
C-19
no aromatic A ring
androgen |
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estradiol
C-18
aromatic A ring |
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18-aldehyde
no 17alpha-OH |
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Term
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cortisol is active form
cortisol increases lipolysis |
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Definition
| there is a correlation between 11beta-HSD in adipose tissue and degree of obesity. why is this? |
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Term
| prevent excessive build up of hydrocortisone (cortisol) and thereby protecting the mineralocorticoid receptors (HC has both mineralocorticoid and glucocorticoid actions) and allowing aldosterone to function normally. |
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Definition
what is the function of 11beta-HSD2 in the kidneys, colon, and salivary glands?
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Term
introduction of a 1,2 double bond: increases GC activity, stable towards 5beta-reductase
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11beta-OH essential for GC activity
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4,5 double bond, 17alpha-OH, 21-OH present in most clinically used glucocorticoids
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introduction of a 9alpha-F dramatically enhances GC activity
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Definition
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Term
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hydrocortisone (GC/MC)
many mineralocorticoids lack 11-OH
9alpha-F increases mineralocorticoid activity
1,2 double bond slight decrease in MC activity
6alpha-methyl decreases MC activity
16alpha-OH, 16alpha-methyl, 16beta-methyl decrease MC activity |
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Definition
| SAR of mineralocorticoids |
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Term
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Definition
| K sparing diuretics (aldosterone antagonists) |
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Term
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C-18 of aldosterone acts as a H-bond donor to the C=O of Asn 770
C-21 OH of aldosterone acts as a H-bond acceptor for the N-H of Asn 770
C-21 OH acts as a H-bond donor to the side chain OH of Thr 945
C-3 C=O of aldosterone acts as a H-bond acceptor to the amide N-H group of Gln 776 |
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Definition
| key interactions of aldosterone binding to the active site of a mineralocorticoid receptor |
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