Clinical Biochem - Unit 1: Lipids and Lipoproteins

Define lipids

• Hydrophobic fats

  • Cholesterol (80%)

  • Fatty acids

  • Triglycerides

  • Phospholipids

Define cholesterol

Unsaturated steroid alcohol on the surface of lipid layers. Synthesized by animals

What is cholesterol’s structure and storage?

• Amphipathic

• Stored as cholesteryl ester

• Free cholesterol is turned into CE by enzymes:

  • ACAT in cells for chylomicrons and VLDL

  • LCAT in blood for HDL

What are the functions of cholesterol?

• Component for cell membrane (keeps integrated)

• Precursors for hormones or bile acids or vitamin D

• Not a source of fuel

• Associated with coronary heart diseases

Define fatty acids

Linear chains of carbon-hydrogen bonds that terminate with a carboxyl group. Make up triglycerides or phospholipids

Describe saturated fatty acids

No double bonds (C-C) (single bonds)

Describe unsaturated fatty acids

• Double bonds (C=C)

  • Monounsaturated: one double bond

  • Polyunsaturated: two or more double bonds

• Typically arranged in cis configuration: in nature, healthy

  • Omega-3, omega-6

• Trans configuration: food processing, artificial

  • Margarine

Describe the features of fatty acids

• Esterified into ester as storage

• Immediate energy substrate, used in triglycerides (energy)

• Solid or oils at room temp

Define triglycerides

Lipids composed of fatty acid molecules attached to a glycerol backbone, hydrophobic

Describe the properties and function of triglycerides

• Solids or oils at room temp

• Neutral lipid

• Major from of fat in adipose tissues

• High-energy storage molecules

• Most prevalent lipid in blood

Describe phospholipids

• Amphipathic

• Structural and functional components

  • Cell membrane and lipoprotein

  • Lung surfactant: phosphatidylcholine (protects lung cells)

Describe lipoproteins

• Lipid and protein molecule complexes

• Spherical structure

  • Central core made of cholesterol esters and triglycerides

  • Apolipoprotein (apoprotein)

• Classification (2 methods)

  • Ultracentrifugation

  • Electrophoresis

In what order are lipoproteins classified in ultracentrifugation (from smallest density/biggest size/smallest proteins/highest lipids)?

1. Chylomicron

2. Very low-density lipoprotein (VLDL)

3. Intermedia density lipoprotein (IDL)

4. Low density lipoprotein (LDL)

5. High density lipoprotein (HDL)

In what order are lipoproteins classified in electrophoresis?

• pH = 8.6 (lipoprotein (-) charge)

• Cathode (-) → anode (+)

1. Chylomicrons

2. Beta - IDL, LDL

3. PreBeta - VLDL

4. Alpha - HDL

Describe chylomicrons

• Largest and least dense produced by intestine

  • 1-2% protein (mainly ApoB-48)

• The turbidity or milky appearance of plasma

• The refrigeration test/standing plasma test

  • Stored at 4°C for over 12 hours or overnight

  • Creamy layer

• Deliver dietary lipids (exogenous TG) to hepatic and peripheral cells (pre- vs post- prandial/before and after meal)

Describe very low-density lipoproteins (VLDL)

• The turbidity or milky appearance of plasma

  • 8-10% protein (Apo-B100, E and C)

  • Produced in liver

  • Major carriers of endogenous TG from the liver to tissue

Describe low-density lipoproteins (LDL)

• BAD CHOLESTEROL

• Produced by liver with various sizes and compositions

  • 20-25% protein (mainly Apo-B100)

• Deliverer of most cholesterol to peripheral cells

• Contribute to atherosclerotic plaques (higher chance of heart attack)

Describe high-density lipoproteins (HDL)

• GOOD CHOLESTEROL

• Smallest and most dense

• 40-50% of protein (mainly Apo-A1)

• Produced by liver and intestine

• Antiatherogenic (removes plaque)

  • Maintain the equilibrium of cholesterol in cells

Describe apolipoproteins (apoproteins)

• Apo A-1, Apo B-48, Apo B-100, Apo C-II, Apo C-III, Apo E

• Alternative to testing for different types of cholesterol

• Contribute to lipid metabolism and transportation

  • Enzyme cofactors (facilitate for enzyme, helps enzymes activate)

  • Ligands of receptors (add ligand for receptor)

Describe Apo A-1

• Alternative to HDL (if we can’t test HDL)

• Primary structural protein of HDL; activates Lecithin-Cholesterol Acyltransferase (LCAT) to promote cholesterol esterification.

Describe Apo B-48

Unique structural protein found on chylomicrons and chylomicron remnants; required for intestinal secretion of dietary lipids.

Describe Apo B-100

• Alternative to calculated LDL

• Primary structural protein of liver-derived lipoproteins (VLDL, IDL, LDL); acts as the high-affinity ligand for the hepatic LDL receptor.

Describe Apo C-II

Enzyme cofactor that activates Lipoprotein Lipase (LPL) on vascular endothelial cells to hydrolyze triglycerides.

Describe Apo C-III

Inhibits LPL activity and delays the clearance of triglyceride-rich lipoprotein remnants.

Describe Apo E

High-affinity ligand recognized by remnant receptors (LRP-1 and LDL receptor) in the liver, mediating the uptake of chylomicron remnants, IDL, and specialized HDL particles.

Describe lipoprotein(a)/Lp(a)

• Apo(a) + Apo-B100

• Plasma levels of Lp(a) vary widely among individuals, but remain relatively constant within an individual

• Associated with decreased clot lysis (↑ blood clot)

  • Increasing risk of premature CHD and stroke

• Underutilized in clinical practice

  • Recommended for patients with a strong family history of CHD, particularly in the absence of other known risk factors

• Measurement: Immunoassays

  • Problems: no universal criteria

What are the major major pathways in lipid metabolism?

1. Lipid absorption

2. Exogenous pathway

3. Endogenous pathway

4. Reverse cholesterol transport

• 1, 2, and 3 are ApoB dependent

  • Atherosclerosis

• 4 is the principal way to maintain the cholesterol equilibrium in peripheral cells