Cholesterol, Lipoproteins & Eicosanoids (Ch. 18.3–18.6, 22.7)

What is cholesterol?

A sterol lipid found in membranes and a precursor for many important molecules

Where does cholesterol come from?

• Diet

• De novo synthesis (in all cells)

What are the major functions of cholesterol?

-Membrane structure (fluidity & stability)

-Precursor to:

• Bile acids

• Steroid hormones

• Vitamin D

Where is cholesterol most abundant?

• Brain (myelin)

• Cell membranes

How is cholesterol eliminated from the body?

Converted to bile acids → excreted via liver/gallbladder

Why is cholesterol important clinically?

High levels → atherosclerosis → heart disease & stroke

What is the key regulatory enzyme for cholesterol synthesis?

HMG-CoA reductase (rate-limiting step)

What is the pathway overview for cholesterol synthesis?

Acetyl-CoA → HMG-CoA → Mevalonate → Farnesyl PP → Squalene → Lanosterol → Cholesterol

What is mevalonate?

A key intermediate in cholesterol synthesis

How do statin drugs work?

Inhibit HMG-CoA reductase → lower cholesterol levels

Why are lipoproteins needed?

Lipids are not water-soluble → need transport in blood

What are the 5 major lipoproteins?

• Chylomicrons

• VLDL

• IDL

• LDL

• HDL

What is the structure of lipoproteins?

-Core:

• Triglycerides + cholesteryl esters

-Surface:

• Phospholipids + cholesterol + apoproteins

What is the role of apoproteins?

• Enzyme cofactors

• Receptor ligands

What is “good” vs “bad” cholesterol?

• HDL = “good” (removes cholesterol)

• LDL = “bad” (deposits cholesterol in arteries)

What is the backbone of sphingolipids?

Sphingosine (instead of glycerol)

What is ceramide?

The core structure of sphingolipids

What are major sphingolipids?

• Sphingomyelin

• Cerebrosides

• Gangliosides

What happens in ganglioside metabolism disorders?

Leads to neurodegenerative diseases (e.g., Tay-Sachs)

What are eicosanoids?

Signaling molecules derived from arachidonic acid (20 carbons)

What are the two main pathways for eicosanoids?

1. Cyclooxygenase (COX)

2. Lipoxygenase (LOX)

What enzyme produces prostaglandins?

Cyclooxygenase (COX)

What are the two types of COX?

• COX-1 → normal physiological functions

• COX-2 → inflammation

What do prostaglandins do?

• Inflammation

• Pain

• Smooth muscle contraction

• Blood pressure regulation

Are prostaglandins stored?

No, they are made and released immediately

How do NSAIDs (like ibuprofen) work?

Inhibit COX enzymes → ↓ prostaglandins → ↓ inflammation & pain

What are thromboxanes?

Eicosanoids that promote blood clotting

Where are thromboxanes produced?

Platelets

Key function for thromboxanes

• Platelet aggregation

• Vasoconstriction

Why is aspirin used for heart disease?

Inhibits thromboxane → reduces clot formation

What are leukotrienes?

Inflammatory mediators from lipoxygenase pathway

What do leukotrienes do?

• Bronchoconstriction

• Inflammation

• Immune cell recruitment

Which leukotriene is important in immune response?

LTB4 → attracts immune cells

Why are leukotrienes important in asthma?

Cause airway constriction and inflammation

What drugs target leukotrienes in the asthma pathway?

• LOX inhibitors

• Leukotriene receptor blockers

What triggers leukotriene release?

IgE-mediated allergic reactions (mast cells)

What effects do leukotriene cause?

• Edema

• Smooth muscle contraction

• Increased permeability

What stimulates aldosterone production?

Angiotensin II

What does aldosterone do?

• Increases sodium retention

• Increases blood pressure

What is ANF (Atrial Natriuretic Factor)?

Hormone released when blood volume is high

What does ANF do?

• Decreases aldosterone

• Lowers blood pressure

• Increases sodium excretion

Why is ANF important?

Prevents hypertension and fluid overload

How are all these topics connected?

• Cholesterol → hormones, bile acids

• Lipoproteins → transport lipids

• Eicosanoids → signaling molecules (inflammation)

• Hormones → regulate fluid balance & BP