Lipids and Lipoproteins

Lipids and Lipoproteins

• Lipids are compounds that yield fatty acids when hydrolyzed or complex alcohols that can combine with fatty acids to form esters.
• Lipids are carried in the bloodstream by complexes known as lipoproteins because they are not soluble in plasma water.

Fatty Acids

• There are two types of fatty acids: saturated and unsaturated.
• Saturated fatty acids have no double bonds in their hydrocarbon chain.
• Unsaturated fatty acids have one or more double bonds in their hydrocarbon chain, which cause a kink or bend in the chain.

Triacylglycerols

• Triacylglycerols are made up of three fatty acids ester-linked to glycerol.

Phosphoacylglycerols (Phospholipids)

• Phosphoacylglycerols are similar in structure to triacylglycerols, except one of the alcohols of glycerol is esterified by phosphoric acid instead of a fatty acid, forming phosphatidic acid (PA).

Steroids

• Steroids are based on a fused ring system, are rigid in structure, and have no ester linkages.
• Examples of steroids include hormones (testosterone, progesterone, estrogen) and cholesterol.
• Cholesterol is a common membrane lipid, almost exclusive to animal cells, and is very hydrophobic but amphiphilic.

Lipoproteins

• Lipoproteins are classified according to density and electrophoresis migration.
• Lipoproteins differ in their sizes, weights, chemical composition, and atherogenicity (association with heart disease).
• There are four main types of lipoproteins: chylomicrons, VLDL, LDL, and HDL.

Chylomicrons

• Chylomicrons are produced by the intestine and transport dietary lipid from the intestine to fat/muscle cells.
• They are the largest lipoproteins, mostly composed of lipid (almost 90% triglyceride), with 1% protein (mainly Apo-B48, C-II, and E).

VLDL

• VLDL is produced by the liver and transports liver-synthesized fat (mostly triglyceride) to fat/muscle cells.
• VLDL is mainly lipid (55% triglyceride), with 10% protein (Apo-B100, C-II, E), and remnants are cleared by liver Apo-B/E receptors.

LDL

• LDL is produced from IDL with a loss of Apo C-II and transports cholesterol to tissue.
• LDL is taken up by Apo-B receptors, and cholesterol is released; in the liver, this decreases cholesterol synthesis.
• LDL can also be taken up by scavenger receptors on macrophages, leading to the formation of foam cells.

HDL

• HDL is the smallest and most dense lipoprotein, synthesized by the liver and intestine.
• HDL is mainly protein (Apo A-I, A-II), with lipid (cholesterol, phospholipid), and is involved in "reverse transport" of cholesterol from tissue to liver.

Apolipoproteins

• Apolipoproteins are proteins that differ in composition from one lipoprotein class to another.
• Functions of apolipoproteins include activating enzymes involved in lipid metabolism, maintaining structural integrity of lipid/protein complex, delivering lipids to cells via recognition of cell surface receptors.

Laboratory Diagnosis and Reference Ranges

• Total Cholesterol: desirable < 200 mg/dL (< 5.2 mmol/L), borderline high 200-240 mg/dL (5.2-6.2 mmol/L), and high > 240 mg/dL (> 6.2 mmol/L).
• LDL cholesterol can be calculated or measured directly using methods such as Friedewald Calculation or Derived Beta-Quantification, or direct methods that selectively react with HDL cholesterol.