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Biochem + Metabolism > Steroids > Flashcards

Steroids Flashcards

1
Q

What is the parent molecule to all steroids?

A

Cholesterol

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2
Q

What are the 4 main functions of cholesterol?

A

Membrane structure
Bile Acids
Steroid hormones
Vit D

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3
Q

True/False: cholesterol synthesis is not tightly regulated

A

false. It is tightly regulated

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4
Q

What percent of animal cell membranes is cholesterol?

A

30%

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5
Q

What are the 3 main cell membrane functions of cholesterol?

A

-Maintaining cell fluidity
-Important for overall stability, durability, and integrity
-Obviates the need for a cell wall

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6
Q

Define amphipathic

A

having both polar and non polar parts

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7
Q

What are the 3 main components of cholesterols structure?

A
  • polar head: OH group
    -rigid steroid ring structure
    -nonpolar hydrocarbon tail
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8
Q

What part of the cholesterol interacts with polar head groups of phospholipids?

A

the hydroxyl group

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9
Q

What percent of cholesterol is endogenous? dietary?

A

endogenous=1/2 - 2/3
dietary= 1/3-1/2

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10
Q

Where does cholesterol come from in herbivores?

A

biosynthesis

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11
Q

Describe the basic lipoprotein structure

A

-Apoproteins (peripheral and integral)
-TG and cholesterol esters comprise the interior
-Phospholipids, free cholesterol, and apoproteins comprise the surface

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12
Q

What are the 4 main lipoproteins?

A

Chylomicrons
VLDL
LDL
HDL

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13
Q

What are the functions of the 4 lipoproteins?

A

-CM: packaging of dietary lipids, delivery to circulation via lymphatics
-VLDL: Transport TG from the liver to tissues
-LDL: Cholesterol transport from liver to extrahepatic tissues
-HDL: Cholesterol “reverse transport” from tissues to liver

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14
Q

Where are the 4 lipoproteins made?

A

-CM: intestines
-VLDL: liver
-LDL: derived from VLDL so the liver
-HDL: derived from VLDL so the liver

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15
Q

What form does cholesterol exist in the blood?

A

cholesterol esters

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16
Q

Why is cholesterol esterified before transport?

A

The ester group makes cholesterol more hydrophobic, so it makes it easier to package since it will want to be buried inside the lipoproteins

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17
Q

Describe the digestion/absorption of dietary cholesterol

A

same as triglycerides, is absorbed into jejunal mucosal cells from a mixed micelle, esterified in the mucosal cell, packaged into a CM, inters the blood via lymphatics

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18
Q

What enzyme esterifies cholesterol?

A

acyl-CoA cholesterol transferase

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19
Q

What is the fate of cholesterol once it has entered systemic circulation?

A

It is taken up by the liver where it can be temporarily stored or packaged into VLDL for export

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20
Q

What are the 3 main ways cholesterol can leave the liver?

A

-Secreted into VLDL
-Free cholesterol secreted in the bile
-Conversion to bile acids/salts

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21
Q

What enzyme is integral to circulating HDL particles and is involved in the esterification of cholesterol once it enters the HDL particle from tissues?

A

lecithin cholesterol acyltransferase

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22
Q

What 3 ways can you alter blood cholesterol levels?

A

-Saturated fat intake increases LDL cholesterol levels
-Dietary sugars increases the production of LDL by the liver
-Soluble fiver and plant sterols can decrease cholesterol absorption by the GI system

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23
Q

What is the primary route of cholesterol excretion?

A

Biliary excretion

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24
Q

What form is cholesterol excreted as?

A

cholesterol or bile acids

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25
Q

What percent of the excreted+ dietary cholesterol mixture is available for absorption in the gut?

A

~1/3

26
Q

What is the carbon source of cholesterol?

A

Acetyl CoA

27
Q

What is the rate limiting step of cholesterol biosynthesis?

A

HMG-CoA reductase

28
Q

How can dietary cholesterol regulate biosynthesis?

A

it decreases it

29
Q

Where is HMG-CoA reductase present in the cell?

A

the endoplasmic reticulum membrane, with the catalytic domain in the cytosol

30
Q

What 3 things can inhibit HMG-CoA reductase?

A

mevalonate (its direct product)
cholesterol
bile acids

31
Q

What 3 things can cause hypocholesterolemia

A

-inherited conditions
-hyperthyroidism: increased number of LDL receptors, so higher clearance
-severe liver disease: decreased synthesis

32
Q

What is the main cause of hypercholesterolemia in dogs?

A

hypothyroidism: decreased levels of LDL receptors and other effects

33
Q

Where are primary bile acids synthesized?

A

in the liver from cholesterol

34
Q

How is bile acid synthesis regulated?

A

feedback inhibition of their own synthesis and on hepatic cholesterol synthesis

35
Q

How are bile acids converted to bile salts?

A

conjugated with glycine or taurine

36
Q

What are the two primary bile acids made in the liver?

A

chenodeoxycholic acid
cholic acid

37
Q

What is the rate limiting step in bile acid synthesis?

A

cholesterol 7alpha- hydroxylase

38
Q

Where are secondary bile acids made?

A

the intestine

39
Q

What are the 3 secondary bile acids?

A

deoxycholic acid, lithocholic acid, ursodeoxycholic acid

40
Q

True/False bile acid spillover into peripheral circulation is normal after a meal?

A

true

41
Q

What can result in increased levels of circulating bile acids not post prandial?

A

liver dysfunction

42
Q

Quickly describe the life of a bile acid/salt

A

Biles salts form micelles, they are largely reabsorbed in the ileum, then cleared from portal circulation after passing through the liver

43
Q

How are secondary bile acids formed in the intestine?

A

they result from bacterial action in the colon. There is partial dehydroxylation and removal of glycine and taurine to yield deoxycholic acid and lithocholic acid

44
Q

Why is ursodiol used clinically in cats/dogs with hepatobiliary deases?

A

Because ursodeoxycholic acid is relatively hydrophilic and believed to protect the liver from the damaging effects of the two hydrophobic bile acids which are retained on cholestatic disorders

45
Q

Describe bile acids in clinical diagnostics

A

Serum bile acid test used to assess hepatobiliary function. It can give a diagnosis of various liver disorders in which bile acids cannot be cleared by the liver

46
Q

Describe a portosystemic shunt

A

an abnormal blood vessel that allows blood to flow directly from the intestine to the general circulation, bypassing the liver

47
Q

What are 4 signs of a portosystemic shunt?

A

-Failure to thrive
-Stunted growth
-CNS signs
-High protein meal can precipitate an episode

48
Q

Why can a high protein meal precipitate an episode in animals with a portosystemic shunt?

A

Because NH4 is high after protein metabolism and it is not being excreted

49
Q

What are the 3 main functions of bile?

A

-dietary lipid emulsification to aid in digestion
-alkalinizing fluid in the intestine that neutralizes acidic digesta from stomach
-excretion

50
Q

What are the 3 main steroid hormones

A

-mineralcorticoids
-glucocorticoids
-sex steroids

51
Q

Where are steroid hormones mainly produced?

A

adrenal cortex

52
Q

cholesterol is needed as a substrate to synthesize steroid hormones, what are the donating pools of cholesterol for this process?

A

-de novo
-circulating LDL or HDL

53
Q

What is the mechanism of action for steroid hormones?

A

affect expression of genes via intercellular receptors

54
Q

steroid hormones act by binding to their receptors with ____ affinity and ____

A

high affinity and specificity

55
Q

How do we use glucocorticoids clinically?

A

highly effective anti-inflammatory medications for allergic rxns, skin conditions, asthma. They are also immunosuppressive

56
Q

What is the clinical use of mineralcorticoids

A

-Tx for addisons disease
-Spironolactone is a mineralcorticoid antagonist

57
Q

Why are estrogens fatal to dogs and cats?

A

estrogens cause fatal bone marrow suppression

58
Q

How do bile acids act as hormones?

A

they bind to specific receptors and affect gene transcription

59
Q

What are the two families of receptors that bile acids can bind to?

A

-nuclear receptors
-cell membrane g protein coupled receptor (mainly brown adipose and intestine)

60
Q

What do bile acids, as a hormone, regualte?

A

glucose, lipid, and energy metabolism

Biochem + Metabolism (15 decks)

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