20 Steroid Hormones: Medicinal Chemistry Duncan Flashcards
How many carbons are in the basic steroid structure?
17
Which position is this carbon in?
1
Which position is this carbon in?
5
Which position is this carbon in?
6
Which position is this carbon in?
10
Which position is this carbon in?
11
Which position is this carbon in?
14
Which position is this carbon in?
15
Which position is this carbon in?
17
Which position is this carbon in?
21
Which position is this carbon in?
19
Which position is this carbon in?
18
Which position is this carbon in?
20
Beta or Alpha?
Alpha
Beta or Alpha?
Beta
Which form is this structure in?
Allo Form
Which form is this structure in?
Normal form
Which form is commonly found in the human body?
Allo form
Cis or Trans?
Trans (up/down)
Cis or Trans?
Trans (up/down)
Cis or Trans?
Cis (down/down)
What is the double bond nomenclature?
Delta symbol or “-ene-“
What are the three main classes of steroid hormones?
Estranes, Androstanes, Pregnanes (glucocorticoids/Progestins)
How many carbons are found in main Androstane structure?
19
How many carbons are found in main Estrane structure?
18
How many carbons are found in main Pregnane (Glucocorticoids/Progestins) structure?
21
What class of steroid is this?
Androstane (Androgen)
What class of steroid is this?
Estrane (Estrogen)
What class of steroid is this?
Pregnane (Adrenocorticosteroid). Requires the -OH group on the 21 carbon to be in the adrenocorticoid family
What class of steroid is this?
Pregnane (Progesterone)
What is the first thing to be named in a structure?
The side chains
What is the second thing to be named in a structure?
Structural class
What is the third thing to be named in a structure?
The double bonds and ketos
What is the chief precursor for all the steroid hormones?
Cholesterol
What is the rate limiting step is the production of cholesterol?
The formation of mevalonic acid catalyzed by HMG-CoA reductase (target of statins)
What needs to happen for Pregnenolone to make Progesterone?
The double bond is in the wrong place (C5=C6), needs to be moved to C4=C5
What are the main things that need to happen to Pregnenolone for it to have high ACH activity?
Needs the double bond to be moved to C4=C5 and REQUIRES the addition of C17 OH group (missing in corticosterone)
How does the biosynthesis of Androgens and Estrogens occur?
Pregnenolone (made from cholesterol) and/or progesterone are converted first to androgenic compounds. These can be further converted into the estrogens. Note: Tissues making lots of estrogens must first make lots of androgens, since these are the starting material (tissues that synthesize large amounts of androgens can have a small amount of estrogens “leak out”)
What needs to happen in the basic steps of steroid catabolism?
Steroids are hydrophobic in large part. To aid in their excretion, they need to be rendered more water soluble. Thus, a major late step in catabolism is linking hydrophilic molecules such as glucuronic acid or sulfate
What happens in the catabolism of ACSs?
Removal of C4=C5 double bond, then the C3 =O; and also the C17-beta side chain (-COCH2OH)
What happens in the catabolism of Estrogens?
Converted to either estriol (addition of C16 -OH) or a C2 methoxy, C17 keto metabolite
What happens in the catabolism of Androgens (i.e. testosterone)?
C4=C5 double bond and the C3 keto are reduced. 17 hydroxy is reveresed
How can the use of tests determine if someone is taking exogenous testosterone?
There is typically a 1:1 ratio of testosterone to its metabolite epitestosterone in the urine. Using exogenous testosterone-generating steroids increases testosterone, but has not effect on epitestosterone. A ratio of T:epi of greater than 1 is indicative of steroid use, a ratio of > 4:1 is taken as evidence of abuse, illegal
