Midterm II: Steroid Hormone Synthesis (Ben) Flashcards
What kind of reactions are most of the reactions in steroid synthesis?
Catalyzed by what type of enzymes?
And what is the general formula for these rxns?
Hydroxylations** catalyzed by **CYP450 enzymes
Where are steroid hormone synthesis reactions located within the cell?
ER or Mitochondria
What is the 2nd most frequent reaction type in steroid hormone synthesis?
Via what kind of enzyme + co-factor?
Oxidoreduction reactions
Via dehyrogenase** enzymes using **NAD+
What is the electron donor molecule in the CYP450 enzymes?
And what special part of the enzyme transfers the electrons?
NADPH donates electrons
- Heme-iron in CYP450 enzyme transfers electrons twice during the hydroxylation reactions
CYP450 needs another enzyme to transfer key elements of the reaction to it.
What is the enyzme?
What does it transfer and how?
CYP450 Reductase
- transfers 2 electrons** **one by one from NADPH
What is the general name of the entire enzyme complex shown here?
Microsomal Electron Transport Chain
- because it consists of the CYP450 reductase enzyme which transfers electrons to the CYP450 enzyme
What are the components of the mitochondrial (not microsomal) electron transport chain involved in some CYP450 steroid synthesis reactions?
In what organ is this chain found?
Found on adrenal mitochondria…
Adrenodoxin Reductase - takes electrons from NADPH to adrenodoxin
Adrenodoxin - an iron-sulfur protein which transfers electrons to the CYP450
What is the first step in the synthesis of all steroid hormones?
Reactants?
Enyzme?
Product?
(Include # of Cs)
Cleavage of cholesterols side chain…
Reactants: Cholesterol (27C) + 3 NADPH + 3 O2
Enzyme: P450SCC Side Chain Cleavage Enyzme
Product: Pregnenolone + Isocaproaldehyde + 3 NADP+ + 3 H2O
Why are 3 NADPH used in the side chain cleavage enzyme reaction?
Because it is a 3 step reaction:
- Hydroxylation of C22
- Hydroxylation of C20
- Cleavage of bond between C20 and 22
Where is P450SCC located?
the inner mitochondrial membrane
How is cholesterol transported into the mitochondria for steroid hormone synthesis?
What is the name of the condition resulting from a lack of the molecule necessary for this?
StAR
(Steroidogenic Acute Regulatory Protein)
- if this is missing = Congenital Lipoid Adrenal Hyperplasia
What two hormones signal increased steroid hormone production?
In which tissues?
- ACTH - adrenal gland
- LH - testes, ovaries
How do LH and ACTH induce steroid hormone synthesis?
(One route leading to 2 effects)
induction of cAMP increase
- induces StAR activation
- activates PKA which phosphorylates/activates cholesterol esterase
What two actions does the P450c17 enyzme have?
17-hydroxylase
and
17,20 lyase
What two reactions are performed by the 17 hydroxylase activity of the P450c17 enzyme?
Pregnenolone —-> 17OH Pregnenolone
Progesterone —-> 17OH Progesterone
What two reactions are performed by the 17,20-lyase activity of P450c17?
17OH Pregnenolone —> DHEA (dehydroepiandrosterone)
17OH Progesterone —> androstenedione
What 3 reactions are catalyzed by 3-Hydroxysteroid Dehydrogenase (3OHSDH)?
And what happens in these reactions?
Transfers double bond from B ring to A ring + dehydrogenates the 3-OH
Pregnenenolone —> Progesterone
17OH Pregnen —> 17 OH Progest
DHEA —> Androstenedione
What is the activity of the P450c21 enyzme?
21 hydroxylase
- hydroxylates the LAST carbon of progesterone and 17OH progesterone