Cholesterol Metabolism

Front 1

What are the synthesis steps, with associated enzymes, leading to cholesterol synthesis?

Back 1

HMG-CoA (by HMG-CoA Synthase)
Mevalonic Acid (by HMG-CoA Reductase *rate limiting)
Cholesterol (from Mevalonic acid)

Front 2

What is the rate limiting enzyme in cholesterol synthesis?

Back 2

HMG-CoA Reductase

Front 3

How is cholesterol eliminated?

Back 3

As bile salts

Front 4

What are the functions of cholesterol?

Back 4

structural component of cell membranes, precursor to bile acids, steroid hormones, and vitamin D

Front 5

Which organ is most responsible for regulating cholesterol homeostasis?

Back 5

The liver

Front 6

What are the body's major sources of cholesterol?

Back 6

dietary cholesterol, de novo cholesterol by extrahepatic tissues (HDL) and the liver

Front 7

How is cholesterol eliminated from the liver?

Back 7

as unmodified cholesterol in bile, converted to bile salts and secreted into the intestinal lumen, becomes a component of plasma lipoproteins (e.g., VLDLs)

Front 8

What is a cholesterol ester (CE)?

Back 8

an esterified cholesterol, which makes it more hydrophobic than free cholesterol

Front 9

How are cholesterol and CEs transported?

Back 9

in lipoprotein particles or bile micelles

Front 10

Where is cholesterol synthesized?

Back 10

by virtually all tissues, but liver, intestine, adrenal cortex, and reproductive tissues make most (this occurs in the cytoplasm)

Front 11

Under what conditions is cholesterol synthesized?

Back 11

during the fed state, where ATP and NADPH are available

Front 12

How is HMG CoA synthesized?

Back 12

Acetyl CoA → acetoacetyl CoA (HMG CoA synthase) → HMG CoA

Front 13

How is mevalonic acid synthesized from HMG CoA?

Back 13

HMG CoA (HMG CoA reductase + 2 NADPH) → mevalonic acid
-irreversible-

Front 14

How is cholesterol synthesized?

Back 14

19 enzyme pathway that is very ATP, NADPH dependent

Front 15

How is cholesterol synthesis regulated (rate limiting enzyme)?

Back 15

HMG-CoA reductase (active in fed state, when dephosphorylated)

Front 16

What is the effect of SREBP on HMG-CoA reductase?

Back 16

a transcription factor that binds the HMG-CoA reductase gene, increases expression → more cholesterol

Front 17

What effect does cholesterol have on the mRNA of HMG-CoA reductase?

Back 17

shortens its protein half life → less cholesterol

Front 18

What effect does insulin and glucagon have on HMG-CoA reductase?

Back 18

insulin activates HMG-CoA reductase by dephosphorylation → more cholesterol, glucagon has an opposite effect

Front 19

What effect does obesity have on cholesterol synthesis?

Back 19

obesity leads to insulin resistance in muscle and adipose, but NOT liver → accelerated hepatic de novo cholesterol synthesis

Front 20

What do statin drugs do to plasma cholesterol levels? How do they do this?

Back 20

statins (HMG-CoA analogs) lower plasma cholesterol by competetively inhibiting HMG-CoA reductase

Front 21

What is the rate limiting enzyme of bile acid synthesis and what does it do?

Back 21

cholesterol 7-(alpha)-hydroxylase, adds hydroxyl group at 7 position of steroid ring

Front 22

7-(alpha)-hydroxyl cholesterol is converted to what two primary bile acids?

Back 22

chenodeoxycholic acid, cholic acid

Front 23

Bile acids are conjugated with two amino acids to form two bile salts. What are they?

Back 23

chenodeoxycholic acid + taurine → taurochenodeoxycholic acid
cholic acid + glycine → glycholic acid

Front 24

What are bile salts taurochenodeoxycholic and glycholic acid used for?

Back 24

digestion (emulsification) and absorption (micelles) of dietary lipids, and the excretion of hydrophobic waste in bile

Front 25

What do intestinal flora do to bile salts?

Back 25

deconjugate them back to bile acids, convert primary bile acids to secondary bile acids, deoxycholic and lithocholic acids

Front 26

Which are better emulsifiers: bile acids or bile salts?

Back 26

bile salts (more polar)

Front 27

Where do primary and secondary bile acids and bile salts get reabsorbed?

Back 27

the ileum

Front 28

What are the treatments for hypercholesterolemia?

Back 28

statin drungs, weight loss, cholestyramine

Front 29

What is cholestyramine's effect on cholesterol?

Back 29

prevents reabsoption of bile salts, thereby forcing the liver to use more cholesterol for bile salt synthesis (lowers cholesterol)