Cholesterol

Structural roles of cholesterol

Membrane component; precursor for bile acids.

Vitamin derived from cholesterol

Vitamin D.

Hormone classes from cholesterol

Steroid hormones (corticosteroids, androgens, estrogens).

Lipoprotein delivering most cholesterol

LDL.

Lipoprotein accepting cholesterol from cells

HDL (via ApoA).

Form of most circulating cholesterol

Cholesterol esters.

Reason cholesterol esters are favored in transport

They package better inside lipoprotein cores.

Can the sterol ring be used for energy?

No.

How excess cholesterol is eliminated

Converted to bile acids and excreted.

Bile synthesized from

Cholesterol (with bilirubin as a major component of bile).

Main function of bile acids in digestion

Emulsify dietary fat.

Where bile acids are made

Liver.

Percentage of endogenous cholesterol

~80%.

Percentage of dietary cholesterol

~20%.

Carbon source feeding cholesterol synthesis

Acetyl-CoA.

Key rate-limiting enzyme in synthesis

HMG-CoA reductase.

Drug class inhibiting HMG-CoA reductase

Statins.

Example of a statin

Atorvastatin (Lipitor).

Effect of rising dietary cholesterol on synthesis

Endogenous synthesis decreases.

Why diet alone has modest impact on total cholesterol

Inverse regulation compensates.

Effect on HMG-CoA reductase when cell free cholesterol increases

Activity decreases.

Effect on LDL receptors when cell free cholesterol increases

Downregulated (fewer receptors).

Effect on cholesterol transfer to HDL when cell cholesterol rises

Transfer to ApoA/HDL increases.

Effect on bile acid formation when cell cholesterol rises

Conversion to bile acids increases.

Clinical consequence of chronically high cholesterol in arteries

Atherosclerosis.

Cholesterol's role in gallstones

Major component—supersaturation forms stones.

Condition favoring gallstone formation

Bile supersaturated with cholesterol.

One bile constituent besides cholesterol

Bilirubin (also bile acids, lecithin/phospholipids).

Organ making corticosteroids from cholesterol

Adrenal cortex.

Organ primarily making androgens from cholesterol

Testes.

Organ primarily making estrogens from cholesterol

Ovaries.

Can each steroidogenic organ make all steroids?

They make small amounts broadly, but each specializes.

Example of an estrogen derived from cholesterol

Estradiol.

LDL's main role

Delivers cholesterol to peripheral tissues.

HDL's referenced role

Accepts cholesterol from cells (reverse transport).

Reason cells reduce LDL receptors when cholesterol is high

To limit further cholesterol influx.

Immediate fate helping move cholesterol out of cells

Esterification/transfer into HDL for transport.

Why we can't "burn" cholesterol for ATP

Sterol nucleus isn't catabolized for energy.

End result of cholesterol homeostasis failure in bile

Gallstone formation and possible biliary obstruction.

Two levers that lower body cholesterol burden

Decrease synthesis (HMGICoA reductase) and increase bile acid formation/excretion.