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Block 3 Week 6 > Blomquist Steroid/Hormone Biochem > Flashcards

Blomquist Steroid/Hormone Biochem Flashcards

1
Q

Do we synthesize the majority of the cholesterol we use?

A

nope

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2
Q

What is produced directly from cholesterol and is the precuroser to all C18, C19, C21 and IS NOT a hormone itself?
How do we make this from cholesterol?

A

pregnenolone

Cut off the carbon side chain and add a ketone

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3
Q

How many C21 carbons are there and what are they called?

A

3

pregnanes

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4
Q

What are the 3 pregnanes (C21 carbons)?

A

progesterone, aldosterone, cortisol

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5
Q

How do you make progesterone?

A

it is made from pregnenalone
Made by moving the double bond from the 5th carbon to the 4th carbon. ANd by trading out the hydroxyl group on position 3 for a ketone.

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6
Q

What does progesterone do?

A

it is secreted from the corpus luteum (the left over follicle from ovulation) and is responsible changes in luteal phase (phase after which the egg has left the follicle and you have the corpus luteum secreting progesterone to aid the endometrium in preparation of having a baby) of menstrual cycle and is the tells the mammary glands to develop in preparation for a baby

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7
Q

What is cortisol and how is it synthesized?

A

this is a preganane (C21) and it is made from progesterone by adding hydroxyl groups to position 11 and 17 and by modifying C21

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8
Q

(blank) is the dominant glucocorticoid in humans, synthesized from progesterone in the zona fasculata of adrenal cortex, involved in stress adaptiation, elevates blood pressure and sodium uptake, and has numerous effects on the immune system.

A

cortisol

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9
Q

How do you remember what are secreted from where in the adrenal glands?

A

GFR it goes salty to sweet to sweetest

Aldosterone, cortisol, sex

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10
Q

What is aldosterone and how do you make it?

A

it is a pregnane and is made from progesterone by adding hydroxyl groups to carbon 11 and 21 and adding ketone groups to 19 and 20

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11
Q

What are C19 steroid hormones called?

A

androstanes

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12
Q

What is this and how is it made:
An androgen, male sex hormone synthesized in the testes, responsible for secondary male sex characteristics, produced from progesterone

A

testosterone

It is made from progesterone with a loss of carbons 20 and 21

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13
Q

What are C18 steroid hormones called and what is the most important one and what does it do?

A

estranes
estradiol
It is an estrogen, made in the ovary responsible for female sex characteristics

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14
Q

Explain the construction of estradiol?

A

made from progesterone and then the C20 and 21 are cleaved and the C19 methyl group is lost and it has an aromatic ring

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15
Q

If there is an aromatic ring in a steroid hormone which way does the the ring point?

A

up (for aromatic)

down (for non aromatic)

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16
Q

What are used in steroid hormone biosynthesis and what is it?

A

cytochrome p450

heme containing membrane bound proteins used for hydroxylation reactions in the creation of cholesterol and steroids

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17
Q

Where do we usually find cytochrome p450?

A

in SER of Liver and Lungs and Mitochondria

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18
Q

(blank) is an inducible enzyme with broad substrate specificity and works in conjunction with a reductase to allow electrons to flow from NADPH to FADH2 Cytochrome P reductase to a P450

A

Cytochrome P450

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19
Q

How many cytochrome p450s do humans have ?

A

57

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20
Q

What reaction does Cytochrome P450 catalyze?

A

it take a substrate and adds a Hydroxyl group to it via the reduction of NADPH and the production of a water molecule

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21
Q

What does CYP11A1 do (mitochondrial CYT P450)? What happens if you dont have this?

A

it cleaves the 6 carbon side chain of cholesterol to produce prenenolone.
Fatal in utero (it is essential)

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22
Q

All steroid hormones are derived from (blank) and undergo (blank) to become corticosteroids and minercorticoids

A

pregnenolone

hydroxylations ( 17, 21, 11)

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23
Q

How do you make sex hormones?

A

removes carbons 20 and 21, turn the hydroxyl group on 3 to a ketone (testosterone), aromatase (estradiol)

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24
Q

Explain how we get to the synthesis of steroid hormones?

A

signal from hypothalamus-> pituitary-> tropic hormones-> bind to cell-» induce second messangers (cAMP or PIP3) -> PKA and phosphorylation-> activation and synthesis of steroid hormones-> hormones bind to plasma proteins and are kept from degredation

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25
Q

What cells produce testosterone?

A

leydig cells

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26
Q

What are the hormones that regulate steroid hormone production and what do they effect?

A

ACTH: cortisol
LH: progesterone and testosterone
FSH: estradiol
Angiotensin: aldosterone

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27
Q

What are released at the nanogram levels?

A

pituitary hormones

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28
Q

Explain how we get cortisol from ACTH?

A

ACTH uses cAMP,PI and Ca as second messengers to stimulate PKA and trigger the zona fascicula of the adrenal gland to produce cortisol

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29
Q

Explain how we get aldosterone from the renin angiotensin system

A

renin angiotensins system secretes angiotensin II and III which activate PI and Ca to start a second messanger cascade which will stimulate PKC to activate aldosterone synthesis and release from the zona glomerulose from the adrenal gland

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30
Q

Explain how testosterone is made via signal from the hypothalamus

A

hypothalamus triggers LH to start a 2nd messenger cascade via cAMP to tell Leydigs cells to produce testosterone

31
Q

Explain how estradiol is made via LH signals?

A

LH starts a 2nd messenger cascade via cAMP to tell ovarian follicle to make estradiol

32
Q

Explain how progesterone is made via LH signals?

A

LH starts a 2nd messenger cascade via cAMP to corpus luteum to make progesterone

33
Q

Explain how we get 1,25 dihydroxy D3 (calcititriol)

A

sunlight, PTH, Ca all trigge PTH to be released and tell cAMP to tell the kidney to make 1,25 dihydroxy D3

34
Q

Can peptide hormones cross cell membranes?

A

no

35
Q

Explain how the PI cycle works?

How does the cAMP work?

A

hormone bind receptor which causes phospholipase A2 to be activated to cause DAG and IP3 to mobilize calcium and increase activity of protein kinase
Hormone stimulates g protein which stimulates AC which stimulates cAMP which stimulates PKA

36
Q

When you have protein Kinase A all activated what happens?

A

you start phosphorylating things such as cholesterole esterase (which increases its activity)

37
Q

What happens if you phosphorylate cholesterol esterase?

A

increase its activity which will increase ester concentration. Now we need to put cholesterol into the mito membrane so we need STAR (a transport protein for cholesterol and thus regulatory protein).THen once inside mito membrane we hit up the side chain cleavage enzyme which will create pregnanolone and thus the steroid hormone synthesis begins

38
Q

What happens if you have LCAH?

A

lipoid congenital adrenal hyperplasia is when your STAR doesnt work and so you dont get adrenal and gonandel steroid production

39
Q

Where do you mostly find STAR (steroidogenic acute regulatory protein)?

A

testes, ovaries and adrenals

40
Q

What is the rate limiting step of steroid hormone synthesis?

A

Star, it allows cholesterol to enter mitochondria to be made into steroid hormone

41
Q

How do we get vit D?

A

7DC is synthesized in liver then UV light converts this to Pre D3, sponatneously converted to D3 via 25 hydroxylase in liver (via cytochrom P450s) then to active D3 in the kidney

42
Q

What three organs participate in getting active form of vit D?

A

liver, kidney and skin

43
Q

What is the major effect of vit D?

A

vit D will bind to DNA and cause transcription of genes to stimulate Ca and phosphate absorption from the lumen and increase Ca pump molecules and calmodulin

44
Q

How do you transport steroid hormones?

A

via binding globulins and proteins and albumin

45
Q

What does cortisol usually bind to and how much is bound?

A

corticosteroid bindin a2 globulin (transcortin)

85%

46
Q

About 65% of testosterone is bound to a glycoprotein called (blanK)

A

sex hormone binding globulin

47
Q

About 60% of estrogen is bound to (blank)

A

sex hormone binding globulin

48
Q

(blank) is also called testosterone-estrogen binding globulin: this protein helps maintain a high level of testosterone within testes and seminal fluid and is important for development and maturation of sperm

A

Androgen binding protein

49
Q

Progesterone binds primarily to (blank) and (blank)

A

transcortin and albumin

50
Q

(Blank) are a group of hormones that enter into the cell and bind a receptor which is in the cytoplasm and enters together into the nucleus or is already in the nucleus where their highly conserved DNA binding domain attaches to DNA and stimulates expression of genes

A

Hormones of the nuclear receptor family

51
Q

What dont nuclear receptors subfamilies have?

A

conserved trans-activation domains> They instead have really bad trans-activation domain (dont allow other proteins or regulatory proteins to bind)

52
Q

What do the receptors of steroid hormones, Vit D, thyroxine and retinoid receptors belong to?

A

nuclear receptor subfamily

53
Q

Steroid receptors bind to DNA as (blank)

A

homodimers

54
Q

IIn the nuclear receptor subfamily, the (blank) have 8 cysteins in groups of 4 with 2 zn ions called zinc fingers that bind DNA at specific points.

A

DNA binding domain

55
Q

In the nuclear receptor subfamily, the hormone response element (HRE) on DNA have specific (blank).

A

half site sequences

56
Q

Unbound (blank) and (blank) receptors are in cytoplasm and when bound move into the nucleus. All other steroid receptors are in nucleus when unbound.

A

aldosterone and glucocorticoids

57
Q

When you bind to a nuclear receptors in the cytoplasma what happens?

A

the heat shock protein falls off and the receptors becomes activated and enters with the hormone into the nucleus

58
Q

What do heat shock proteins do?

A

they block the DNA binding site of the receptor

59
Q

Where do we find zinc fingers?

where do the hormones bind to the receptor?

A

DNA binding domain

Ligand binding domain

60
Q

DO the different nuclear receptors have alot of homology?

A

yeah like around 60%

61
Q

(blank and blank) have the same kind of receptors as steroid receptors.

A

retonic acid (vit A) and triiodothyronine (T3)

62
Q

What is this:
adrenal insufficiency resulting
from progressive lesions in the adrenal glands

A

addisons disease

63
Q

What is this:

increased cortisol secretion due to tumor on the pituitary gland

A

cushings disease

64
Q

What is this:
loss of function in synthesis of adrenal cortex hormones resulting in accumulate of steroid intermediates. Typically due to loss of 21 hydroxylase or 11 hydroxylase

A

congential adrenal hyperplasia (CAH)

65
Q

(blank) is a secosteroid with an open ‘B’ ring and 27 carbons

A

Vitamin D

66
Q

(blank) is a C18 steroid with an aromatic ‘A’ ring

A

Estrogen

67
Q

The unbound receptor for glucocorticoids and probably aldosterone are in cytoplasm and (blank) and move to nucleus after steroid hormone binds

A

dimerize

68
Q

Steroid hormone receptors function as (blank)

A

dimers

69
Q

The C21 hormone are (blank X 3)

A

aldosterone, cortisol, progesterone

70
Q

Androgens (including testosterone) are (blank) steroids

A

C19

71
Q

What kind of hormones regulate steroid hormone synthesis and how?

A

peptide (from anterior pituitary) via 2nd messangers (cAMP and PIP3)

72
Q

How do steroid hormones travel in the blood?

A

bound to proteins

73
Q

Steroid hormone receptors have what 2 binding domains?

A

ligand and DNA

Block 3 Week 6 (6 decks)

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