14_Biochem Block 3.5 Steroid Hormones

Front 1

Describe the two precursors of the five steroid hormones - including the number of C

Back 1

Cholesterol (C27) --> Pregnenolone (C21) -->
1. Progestins (C21)
2. Glucocorticoids (C21)
3. Mineralcorticoids (C21)
4. Androgens (C19)
5. Estrogens (C18)

Front 2

Where are each produced?
1. Progestins (C21)
2. Glucocorticoids (C21)
3. Mineralcorticoids (C21)
4. Androgens (C19)
5. Estrogens (C18)

Back 2

1. Progestins (C21) - Placenta-ovary-corpus luteum
2. Glucocorticoids (C21) - adrenal cortex
3. Mineralcorticoids (C21) - adrenal cortex
4. Androgens (C19) - testes
5. Estrogens (C18) - estrogen

Front 3

Synthesis of steroids in the adrenal cortex requires a lot of this: Therefore, the adrenal cortex requires an active ? pathway.

Back 3

Requires a lot of NADPH and therefore requires an active Pentose Phosphate pathway.

Front 4

The adrenal glands is under stimulation by this hormone that is from the anterior pituitary gland. This hormone is what kind of hormone?

Back 4

Adrenocorticotropic hormone (ACTH or "corticotropin" - a 39 aa hormone)

Front 5

What does ACTH stimulate?

Back 5

Conversion of cholesterol to pregnenolone.

Front 6

Where does the first step of hormone synthesis take place?

Back 6

The matrix side of the inner mitochondrial membrane.

Front 7

What enzyme catalyzes the synthesis of pregnenolone?

Back 7

Desmolase, or Cholesterol Desmolase Cytochrome P450scc (side-chain cleavage)

Front 8

How many molecules of NADPH and O2 is required in the 1st step of steroid hormone synthesis?

Back 8

3

Front 9

What are the rxns in the 1st step of steroid hormone synthesis?

Back 9

Cholesterol --> 20a-Hydroxycholesterol --> 20a-22R-Dihydroxycholesterol --> Pregnelone + R (whatever side group)
Note: Each rxn consumes an NADPH and O2

Front 10

What kind of enzyme is Cytochrome P450? What kind of rxn does it carry out?

Back 10

Heme-containing monooxygenase. Hydroxylation rxn

Front 11

What does P450 use NADPH for?

Back 11

To activate an O2 for use in the hydroxylation rxn.

Front 12

Describe the the electron transport chain rxn that transfers an electron from NADPH to P450 to allow it to activate O2 (p275)

Back 12

NADPH transfers electron to Adrenodoxin Reductose (FAD, Flavo-protein), that transfers electron to Adrenodoxin (Iron-Sulfur Protein), that transfers electron to P450. P450 is now activated and capable of hydroxylating Cholesterol.

Front 13

She wants us to know what the electron transport chain for NADPH electron transfer to P450 looks like in the mitochondria. Draw it - it's on the opposite of this card.

Back 13

a

Front 14

What is the role of SR-B1

Back 14

Extract cholesterol esters from HDL

Front 15

Cells of the adrenal cortex express high levels of this receptor: (p276)

Back 15

LDL receptor

Front 16

Describe the electron transport chain rxn that happens in the ER membrane.

Back 16

NADPH transfers 1 electron to NADPH Cyt P450 Reductase. It then transfers electron to Cyt P450. Then, electron is used to activate O2 for hyroxylation rxn.

Front 17

Where does the 2nd electron transfer system for cholesterol hormone synthesis take place?

Back 17

ER

Front 18

Note: For glucocorticoids and Progestagens biosythesis, she wants us to know the structures of Cholesterol, Progesterone, Corticosterone and Cortisol. Also, the enzymes involved at each step. What's this first one?

Back 18

Progesterone

Front 19

What structure is this?

Back 19

Corticosterone

Front 20

What is the difference between these two molecules? What is one the L and what is on the R?

Back 20

Only difference is the additional OH group at the 17 position.
L = Cortisol
R = Corticosterone

Front 21

How are steroids inactivated and excreted? (p280)

Back 21

1. In liver, their ketone groups/double bonds are reduced
2. They are conjugated with Glucuronic Acid or Sulfate - making them water soluble and readily excreted.

Front 22

Describe Congenital Adrenal Hyperplasia (CAH):
1. Inheritability/Incidence
2. A deficiency in enzyme necessary to make:
3. This enzyme deficiency accounts for 90% of the CAH cases:
4. 75% of pts cannot synthesize: Most die in neonatal period from:
5. 25% of pts exhibit progressive:
6. Treatment option:

Back 22

1. Autosomal recessive (1:40,000)
2. Cortisol
3. Deficiency in 21-hydroxylase
4. Aldosterone deficiency; Salt wasting leads to shock
5. 25% exhibit progressive virilism
6. Hormone replacement - administer glucocorticoids, aldosterone

Front 23

Describe Addison's Disease
1. About how many people in US have it?
2. Caused by destruction of:
3. Two diseases that lead to it:
4. Symptoms include:
5. Treatment:

Back 23

1. 10,000
2. Caused by destruction of the adrenal cortex
3. Autoimmune Adrenalitis; Tuberculosis Adrenalitis
4. Fatigue, muscle weakness, weigh loss, low BP, hyperpigmentation
5. Replacement therapy; administer glucocorticoids, aldosterone.

Front 24

Describe Cushing's Disease
1. Caused by a tumor in the: This results in excess levels of: This, in turn, leads to excess production of:
2. Symptoms include:
3. Treatment

Back 24

1. Caused by tumor in the anterior pituitary producing too much ACTH; this leads to excess cortisol
2. Sudden onset of weigh gain, muscle wasting, and weakness
3. Microadenomectomy; pituitary irradiation, adrenalectomy.