9 - Steroids

Question 1

What is included in the basic steroid template?

Answer 1

4 rings (sterane) and 2 methyl groups positioned at 10 and 13, but are labelled as C-18 and C-19 when both are present

Question 2

What happens to 1,2-disubstituted cyclohexanes?

Answer 2

• Can be cis (same side) or trans (across from each other)
• Trans will be axial-axial or equatorial-equatorial
• Cis will be axial-equatorial

Question 3

What is the relative configuration along the backbone of all biologically active steroids?

Answer 3

• a = alpha (below the plane); B = beta (above the plane)

- 5a-10B-9a-14a-13B

Question 4

What is the geometry of all biologically active steroids?

Answer 4

• Trans-trans-trans geometry at ring junctions

- Anti-anti geometry for adjacent ring junctions

Question 5

What is the ideal shape for a polycyclic steroid?

Answer 5

• Rigid “rod” shape is biologically active and more stable (alpha)
• Rigid “bent” shape is not active and less stable (beta)

Question 6

What are the rules for nomenclature of double bonds of steroids?

Answer 6

• Give the position from which the double bond originates
• If the double bond points to any other position other than the next highest number, the atom where the bond terminates must be given

Question 7

What are the 3 rules for steroid classes?

Answer 7

1) Carbon at C-17? (androstane and estane = no)
2) Methyl at C-10? (androstane = yes; estane = no)
3) If there is a carbon at C-17, is it a 2 carbon chain or 8 carbon chain? (pregnane = 2 C’s; cholestane = 8 C’s)

Question 8

What are the main steroid hormone actions?

Answer 8

1) Follicle stimulating hormone and luteinizing hormone in ovaries or testes
2) Corticosteroids in adrenal cortex

Question 9

How do steroids travel in blood?

Answer 9

Travel attached to protein carriers b/c don’t readily dissolve in blood plasma or water

Question 10

Describe the mechanism of steroid hormone actions

Answer 10

1) Steroids are carried to the cell by protein carriers and dissociate near their target cells and bind to a steroid receptor
2) Steroid/receptor complex is carried to nucleus (translocation)
3) Binding of complex to DNA regulatory site
4) Instructs DNA to transcribe mRNA
5) mRNA then delivers its message to ribosomes in cytoplasm to increase protein synthesis (translation)
- OR steroid hormone can enter cell, directly enter nucleus, and bind to steroid receptor already in nucleus

Question 11

Are estrogens, androgens, progestins, and adrenocorticoids needed in low or high concentrations to be effective?

Answer 11

Extremely low (less than 1 nM)

Question 12

What do estrogens, androgens, progestins, and adrenocorticoids have high binding affinity for?

Answer 12

Intracellular hormone responsive elements (short DNA sequence)

Question 13

What are the 2 main subtypes of adrenocorticoids?

Answer 13

Glucocorticoids and mineralocorticoids

Question 14

___ serves as the starting point for all steroid hormones that are produced in the body

Answer 14

Cholesterol

Question 15

What is cholesterol an essential component of?

Answer 15

• Animal cell membranes

- Acts as spacers to fill in the gaps to stabilize the membrane

Question 16

What is glycocholate? Where is it stored? What is its function?

Answer 16

• Bile salt
• Stored in gallbladder
• Acts as emulsifier of fats in enterohepatic circulation; also a negative feedback control on 7 alpha-hydroxylase enzyme

Question 17

What is the function of bile acids and phospholipids?

Answer 17

• Solubilize cholesterol in bile, preventing precipitation of cholesterol in gallbladder
• Act as emulsifying agents, rendering fats accessible to pancreatic lipases
• Facilitate intestinal absorption of fat-soluble vitamins/drugs
• Involved in the control of their own metabolism and transport via enterohepatic circulation

Question 18

What is the function of vitamin D?

Answer 18

Induces P-glycoprotein transporters in GI tract, which enhance bile reabsorption to blood and liver

Question 19

What is the role of the enterohepatic circulation w/ respect to recycling of steroids, lipids, and drugs?

Answer 19

• About 97% of cholesterol and steroid hormones are reabsorbed
• Uptake of dietary lipids and fat-soluble vitamins; all solubilized by bile salts in intestine
• Recycles most non-polar drugs/ metabolites and bilirubins

Question 20

What is the enterohepatic circulation pathway?

Answer 20

Liver -> bile ducts -> gall bladder -> small intestine (reabsorption through GI wall to portal vein) -> liver

Question 21

How much liver is absorbed and produced by the body daily?

Answer 21

• 300 mg absorbed from gut daily

- 800 mg produced by body

Question 22

What are the 3 ways to lower cholesterol? What drugs are used for each mechanism?

Answer 22

1) Decrease production (statins)
2) Decrease absorption in small intestine (ezetimibe)
3) Decrease absorption in ileum (bile acid binding resins)

Question 23

What are the main lipids in blood plasma? Can they be taken up into the cell via passive diffusion?

Answer 23

• Cholesterol and cholesterol esters
• Triglycerides
• Phospholipids
• Yes they can be taken up by passive diffusion b/c they are part of the cell wall

Question 24

What is the difference between triglycerides and phospholipids w/ respect to function?

Answer 24

• Triglycerides = storage form of fatty acids

- Phospholipids = membrane lipids

Question 25

Is cholesterol or a cholesterol ester more nonpolar?

Answer 25

Esterification w/ a fatty acid chain makes a molecule more nonpolar

Question 26

How are plasma lipids transported in blood circulatory system?

Answer 26

Lipoproteins

• Spherical macromolecules consisting of carbs, phospholipid monolayer, triglycerides, and cholesterol and its esters
• Lipids are covalently and non-covalently bound to proteins and carbs
• These combinations prevent plasma lipids from forming insoluble aggregates

Question 27

What is HDL called the “good cholesterol carrier”?

Answer 27

Has the highest protein content and lowest triglyceride content

Question 28

Function of chylomicrons?

Answer 28

Transport fat to adipose

Question 29

Function of LDL?

Answer 29

Transport cholesterol to extra-hepatic tissues

Question 30

Function of HDL?

Answer 30

Removal of cholesterol from extra-hepatic tissues to LDL, IDL (intermediate density lipoproteins) /VLDL, and liver

Question 31

How is cholesterol converted into an estrane?

Answer 31

1) C-17 side chain is reduced to a 2-carbon side chain and OH at C-3 is removed and double bond at C5,C6 is removed (forms pregnane)
2) 2-carbon side chain at C-17 is removed (forms androstane)
3) Methyl group at C-10 is removed (forms estrane)