Sterioid Biosynthesis

Question 1

Desmolase

Answer 1

An enzyme that produces pregnenolone from cholesterol

adds =O to cholesterol

Question 2

All steroids are made from what and where

Answer 2

Cholesterol in the Adrenal cortex

Question 3

What regulates Desmolase Activity

Answer 3

ACTH

Stimulates production of pregnenolone from cholesterol

Question 4

What is Pregnenolone made into

Answer 4

Progesterone——>

1. Corticosteroids (Aldosterone-glucocorticoid + Cortisol-mineralcorticoid)
2. Sex Hormones (Testosterone + Estradiol)

Question 5

20,22- Desmolase (cytochrome P450 or CYP11A1)

Action and regulation and where

Answer 5

Catalyze RLS to convert cholesterol to Pregnenolone or other things
In Adrenal glands, testes, ovaries, placenta)
Regulated by ACTH

Question 6

CYPS in animals

Maybe you have to know

Answer 6

CYP1-49 and CYP3001-4999

Question 7

C21

Answer 7

Pregnenolone

Question 8

Aldosterone direct function

Answer 8

Binds to Mineralcorticoid Receptors (MR) to activate it

= causing sodium retention and HTN

Question 9

MR classification

Answer 9

Important Nuclear Receptor Superfamily Member (receptor in nucleus so lipophilic ligands bind to it)

Question 10

5 Hs. That bind to MR

Answer 10

Aldosterone 
11-deoxycorticosterone
Testosterone 
Cortisol (Hydrocotisone)
Cortisone

Question 11

Primary Aldosteronism

Answer 11

CONN’S SYNDROME

Excessive Aldosterone from AC- HTN (Na+ retention and K+ loss)

Question 12

Adrenal Hyperplasia

Answer 12

Mild form is common (not rate as thought)- not easily Dx
1. Classic
2. Non- Classic
= deficiency in adrenal enzymes used to make glucocorticoids
= increase in cortisol and androgen production

Question 13

Adrenal Hyperplasia Sx:

Answer 13

*Hirsutism (in women) = hair on parts of body where excessive hair in not normal
*Oligomenorrhea (in women) = infrequent or very light mentruation (>35days) + infertility at times
Life-threatening sinus/pulmonary infection
Orthostatic syncope
Short
Severe acne

Question 14

When is adrenal hyperplasia Dx in the fetus

Answer 14

Do it while it is in the womb by HLA haplotype

Excessive cortisol in the amniotic fluid

Question 15

Adrenal Hyperplasia Tx:

Answer 15

Monitored H. Replacement Therapy (HRT) = enhance quality of life

Question 16

2 enzymes that can be mutated in adrenal Hyperplasia

Answer 16

1. 21-Hydroxylase

2. 11-B Hydroxylase

Question 17

X 21- Hydroxylase

Answer 17

X Progesterone —> Deoxycorticosterone = ALDOSTERONE
X 17a- Hydroxyprogesterone—> 11-Deoxycortisol = CORTISOL

Increased: progesterone + 17a-Hydroxyprogesterone

Question 18

X 11-B Hydroxylase

Answer 18

X Deoxycorticosterone—> Corticosterone = ALDOSTERONE
X 11-Deoxycortisol —> Cortisol = CORTISOL

Increased Deoxycorticosterone + 11-Deoxycortisol

Question 19

Which CYP is 11-B Hydroxylase

And how does it cause HTN

Answer 19

CYP11B1
Decrease in cortisol and cortisone (X 11B Hydr.)
Increase in 11-Deoxycorticosterone + 11- Deoxycortisol
* 11-Deoxycorticosterone = BINDS TO MR =HTN

Question 20

The Hypothalamic Pituitary Axis for the release of CORTISOL

Answer 20

CRH (hypothalamus)——> ACTH (AP)——> cortisol (Adrenal Glands)——I hypo and AP

Question 21

ACTH binds to what and where in detail

Answer 21

ACTH G-protein receptors on the Zona Fasciculata of adrenal cortex

Question 22

ACTH signal cascade when it binds to a receptor

Answer 22

ACTH——> ACTHR

1. Conformational change of G-Protein
2. Adenylyl cyclase
3. cAMP
4. PKA activated and activated cell proliferation to make cortisol and release it

Question 23

ACTH signaling cascade in tumor cell when it binds to R

Answer 23

PKA is uncoupled from the G-Protein signal cascade and continuously activated cell proliferation and Cortisol release

Question 24

What is CYP17A1 (17,20 -Lyase)

Answer 24

Dual enzyme (17a-Hydroxylase + 17,20-lyase) 
= MAKES Progestins, mineralocorticoids, glucocorticoids, androgens, estrogens

Question 25

X 17,20-lyase

Answer 25

X androgens INCREASE glucocorticoids (especially CORTISOL =adrenal hyperplasia) Increase in 17a-hydroxypregnenolone(making DHEA) + 17a-Hydroxyprogesterone(making Androgenedione) (Mutations in the CYP17A1) = target for prostate cancer drugs

Question 26

Zona Glomerulosa

Answer 26

Aldosterone

Question 27

Zona Reticularis

Answer 27

Androgens

Question 28

How is VIT D made

Answer 28

7-Dehydrocholesterol + Light = VIT D3———> Calcitetrol eventually

Question 29

How is VIT D3 obtained (Cholecalciferol)

Answer 29

1. DIET : Ergocalciferol (VitD2) in GI 2. LIGHT: converted from 7-dehydrocholesterol (ON SKIN) ——> 1,25-Dihydroxycholecalciferon * BY 1-a- Hydroxylase in kidney

Question 30

Active form of VIT D | And where is it stored

Answer 30

Calcitriol 1,25- Dihydroxycholescaliferol In the liver

Question 31

7-Dehydrocholesterol in skin | Details on how it gets converted to active VIT D

Answer 31

1. UV -> Cholecalciferol (VIT D3) 2. LIVER -> VIT D3 ——> 25-hydroxycholecalciferol * 25-Hydroxylase 3. KIDNEY -> 25-Hydroxycholecalciferol ——> 1,25-Dihydroxycholecalciferol

Question 32

Which enzyme does the liver have to convert VIT D3 to a form that it can go to the liver

Answer 32

25- Hydroxylase

Question 33

- and + regulation in kidney to convert 25-HCC to 1,25-DHCC

Answer 33

- Calcitriol (active VIT D) | + PTH, low PO4-3

Question 34

Enzyme in kidney that makes active VIT D

Answer 34

1a- Hydroxylase

Question 35

Which is the protein2 bound form of VIT D

Answer 35

25- Hydroxycholecalciferol that is made in the liver