404: Cholesterol, Steroids, Vitamins, and Eicosanoids

Cholesterol

Weakly amphipathic precursor to steroids and bile salts

Cholesterol transport into cells:

1. Cell synthesizes LDL receptors in ER

2. LDL receptor expression

3. ApoE on LDL binds to receptors

4. LDL internalized and dissociated

5. LDL degraded in lysosome, releasing cholesterol

Isoprenoids

• Cholesterol

• Steroid hormones

• Bile

• Lipid-soluble vitamins

Steroid backbone

4-ringed hydrocarbon

Where is cholesterol synthesized?

Endoplasmic reticulum (start/end) and cytosol (middle) of LIVER

Where do all the carbons of cholesterol come from?

Acetyl-CoA

Intermediates in cholesterol synthesis

Mevalonate, squalene, lanosterol, cholesterol

What activates cholesterol synthesis?

HIGH blood glucose (INSULIN)

Cholesteryl esters

• Fatty acid covalently linked to cholesterol via ester bond

• Hydrophobic

• Found inside lipoproteins

Bile Salts

• Fat emulsifiers

• Amphipathic - has up to 4 hydrophilic groups

  • IONIZABLE R4 GROUP

1st Steroid Hormone from Cholesterol

ALWAYS Pregnenolone (precursor to all steroid hormones)

Side chain of Steroid Hormones

Ketone and/or alcohol (NOT COOH, that would be a bile salt)

NOT IONIZABLE

Where are steroid hormones made?

Endoplasmic reticulum

Vitamin D Structure

Analog of steroid BUT not actually a steroid

MISSING A RING

Only vitamin we can synthesize

Vitamin D (D3)

What is Vitamin D synthesized from?

7-dehydrocholesterol (cholesterol intermediate)

Role of Vitamin D3

Calcium absorption in small intestine and uptake in osteoblasts

Activation of Vitamin D3 occurs from…

Hydroxylation

Lipid-soluble Vitamins

A, D, E, K (isoprenoids)

A, E, and K CANNOT be synthesized

Vitamin A

Synthesized from B-carotene into trans-retinal or trans-retinol

Trans-retinal

Used in vision

Trans-retinol

Highest biological activity in Vitamin A

Eicosanoids

Signaling molecules derived from arachidonic acid, starting from omega-6 FA

Most important eicosanoid

Prostraglandins