Steroids

Question 1

What do steroids act as?

Answer 1

Hormones and surfactants

Question 2

What are steroids derived from?

Answer 2

Triterpenoids

Question 3

How many isoprene units are in farnesyl pyrophosphate?

Answer 3

3

Question 4

How is squalene oxide formed?

Answer 4

Squalene + O2 + NAPDH

Question 5

Why are epoxides reactive?

Answer 5

Very strained angles

Question 6

Why can squalene oxide ring close?

Answer 6

Rotatable bonds allow a cascade of electrons

Question 7

What carbocation is most stable?

Answer 7

Tertiary carbocation

Question 8

What are anti-migrations?

Answer 8

Each group migrates axially and is anti-periplanar to the one before

Question 9

Why is ring-closed squalene likely to occur?

Answer 9

Due to stable tertiary carbocation and chair, boat, chair conformation of 6 membered ring

Question 10

Lanesterol to cholesterol

Answer 10

Alkene reduced, new alkene introduced and methyl groups lost to form CO2

Question 11

Structure of all steroids

Answer 11

3 - 6 membered rings
1 - 5 membered ring

Question 12

Ring junctions in steroids

Answer 12

All ring junctions are trans except A/B rings which can be cis or trans

Question 13

What is the structural drawing of ring junctions?

Answer 13

Trans - groups attached on opposite faces
Cis - groups attached on the same face

Question 14

What are sterols?

Answer 14

Steroids with an alcohol

Question 15

What are the origins of saponins?

Answer 15

Plant origin

Question 16

What is the structure of saponins?

Answer 16

Extra 5-membered ring and spiroketal attached to extra ring

Question 17

Why are saponins like surfactants?

Answer 17

Sugar units act as surfactants as they dissolve in water but the saponin rings are lipophilic

Question 18

What do saponins cause?

Answer 18

Haemolysis

Question 19

What is the ring conformation of cardioactive glycosides?

Answer 19

Cis fused ring system between C/D and A/B

Question 20

What is the additional ring on cardioactive glycosides?

Answer 20

Unsaturated lactone at C-17β

Question 21

What is digitoxigenin?

Answer 21

A cardioactive glycoside used as arrow poison

Question 22

Why are cardioactive glycosides cardioactive?

Answer 22

Sugar unit increases solubility and binding to heart muscle

Question 23

Why do bile acids occur in salt form?

Answer 23

Carboxylic acids so form bile salts

Question 24

What groups are on bile acids?

Answer 24

3a & 7a OH’s
C5 carboxylic acid side chain

Question 25

What are the 2 types of hormones?

Answer 25

Sex and adrenocortical

Question 26

Where are adrenocortical hormones produced?

Answer 26

Adrenal cortex

Question 27

What are the 2 types of adrenocortical hormones?

Answer 27

Glucocorticoids and mineralocorticoids

Question 28

Structure of glucocorticoids?

Answer 28

C21 pregnane structure 17β ketone group with OH 11β OH Conjugation in A ring with =O

Question 29

Structure of mineralocorticoids?

Answer 29

C21 pregnane sgtrucutre 17β ketone group 13β COOH Conjugation on A ring with =O

Question 30

What do mineralocorticoids do?

Answer 30

Control electrolyte balance in kidneys Retention of Na+/Cl- Excretion of K+

Question 31

How is H2O solubility of steroids increased?

Answer 31

Addition of OH and ionised groups

Question 32

How are steroids transported?

Answer 32

Attached to a large protein Bond to a small compound such as a sugar or salt

Question 33

What is pinocytosis?

Answer 33

Cell takes up fluid along with small dissolved molecules

Question 34

What is the process when steroids pass through cell membrane?

Answer 34

Steroid diffuses through cell membrane Attaches to steroid receptor complex Dimerises Translocates to nucleus Binds to chromatin and alters DNA and cell function

Question 35

What does Sex Hormone Binding Globulin transport?

Answer 35

Testosterone and estradiol

Question 36

What does corticosteroid-binding Globulin transport?

Answer 36

Hydrocortisone, aldosterone and progesterone

Question 37

What do LDL contain?

Answer 37

LDL contains higher levels of cholesterol and triglycerides

Question 38

Why are LDL light?

Answer 38

Contains hydrocarbons

Question 39

How many times more cholesterol does LDL have than HDL?

Answer 39

4x

Question 40

What is Phase I of cholesterol metabolism?

Answer 40

Oxidation using CYP450 Alkyl groups lost and COOH formed - polar Reduction of double bond - gives A/B ring cis geometry

Question 41

What is Phase II of cholesterol metabolism?

Answer 41

Addition of polar groups glycine or taurine

Question 42

Where is cholesterol metabolised?

Answer 42

Liver

Question 43

Where are bile salts stored?

Answer 43

Gallbladder

Question 44

Why are bile salts surfactants?

Answer 44

OH groups on alpha face and methyl groups on beta face

Question 45

What % of bile salts are recycled?

Answer 45

95%

Question 46

How many times can each bile salt molecule be reused?

Answer 46

20x

Question 47

What controls stock of bile salts?

Answer 47

Enterohepatic recycling

Question 48

What are the therapeutic properties of glucocorticoids?

Answer 48

Diseases with overactive immune system Reduces swelling, heat and tenderness in cancer treatment

Question 49

What is transactivation with Glucocorticoids?

Answer 49

GC binds to cytosolic GC receptors Receptor-ligand complex translocates to cell nucleus Binds to GCR elements Results in regulation of gene expression

Question 50

What are the effects of proteins that result from transactivation of glucocorticoids?

Answer 50

Anti-inflammatory Increases gluconeogenesis

Question 51

What is gluconeogenesis?

Answer 51

Glucose synthesis from proteins and fats

Question 52

What is transrepression with Glucocorticoids?

Answer 52

GCRs inteact with specific transcription factors Prevents transcription of pro-inflammatory genes including cytokines and chemokines

Question 53

What is a negative effect of GCs?

Answer 53

GCs can affect wanted and unwanted (regulatory) genes

Question 54

How do GCs immunosupress?

Answer 54

Suppress cell mediated immunity Suppresses gene code for cytokines Reduces T cell proliferation Can induce T cell apoptosis

Question 55

How do GCs have an anti-inflammatory effect?

Answer 55

Potent Inhibit prostaglandins and leukotrienes Supress COX I and COX II expression

Question 56

How does the hydrocortisone negative feedback loop work?

Answer 56

Low hydrocortisone levels stimulate corticosteroid releasing factor Stimulates ACTH from pituitary ACTH stimulates biosynthesis of hydrocortisone

Question 57

Where is corticosteroid releasing factor released from?

Answer 57

Hypothalamus

Question 58

What happens when hydrocortisone levels are high?

Answer 58

CRF and therefore ACTH are not produced

Question 59

Side effects of glucocorticoids

Answer 59

Weight gain Irregular periods Cataracts Increased skin fragility

Question 60

Side effects of mineralocorticoids

Answer 60

Hypertension Salt and Water retention

Question 61

What does conjugation of A ring in corticosteroids do?

Answer 61

Increases glucocorticoid activity over mineralocorticoid

Question 62

Halogenation in corticosteroids?

Answer 62

increases both gluco & mineralocorticoid activity

Question 63

Addition of sodium phosphate in corticosteroids

Answer 63

Increases aqueous solubility for IV

Question 64

Methylation at 16 in corticosteroids?

Answer 64

increases glucocorticoid activity but not mineralocorticoid

Question 65

What effect do synthetic progestins have on hypothalamus?

Answer 65

Feedback effect prevents ovulation and stops uterine contractions

Question 66

How can estrogen be improved?

Answer 66

Alkylate phenol on ring A to create prodrug Alkylate c17 to prevent OH becoming ketone

Question 67

What are the key functional groups on oestrogens?

Answer 67

No side chain Aromatic Ring A No methyl group at C10 Ketone or OH at C17

Question 68

What are the key functions on progestogens?

Answer 68

Side chain at C17 Conjugation with A ring and =O

Question 69

What are the key functions on androgens?

Answer 69

No side chain Conjugation with A ring and =O 17β-OH

Question 70

What is estrogen metabolised to?

Answer 70

Estriol and estrone

Question 71

How is progesterone altered to be suitable for oral use?

Answer 71

Addition of Me at C6 Elongate side chain at C13

Question 72

What is Mestranol a pro-drug of?

Answer 72

Ethinylestradiol