Lipids and Lipoprotein Metabolism

Lipids

• Lipids are a type of sugar-containing lipids found in every tissue, especially in the brain and nervous tissue, containing sphingosine as an alcohol in their structure.

Glycolipids

• Glycolipids are sugar-containing lipids with two simplest members: galactosylceramide and glycosylceramide.
• Galactosylceramide is the main glycolipid of the brain and other nervous tissues.
• Glycosylceramide is a simple glycolipid predominantly found in non-nerve tissues.
• Gangliosides are glycolipids with an oligosaccharide attached instead of a monosaccharide, found mainly on the outer surface of nerve cell membranes.
• Gangliosides contain one or more sialic acid (9-carbon amino sugar) molecules.

GM1 Ganglioside

• GM1 is a member of the ganglio series of gangliosides, containing one sialic acid residue.
• GM1 has important physiological properties, impacting neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain.
• GM1 acts as the site of binding for both cholera toxin and E. coli heat-labile enterotoxin (Traveller's diarrhea).

Lipoproteins

• Apolipoproteins play various roles, including forming the structural part of lipoprotein, acting as enzyme cofactors, and as ligands in interaction with lipoprotein receptors in tissues.
• Apo B is an indispensable substance in the formation of chylomicron and VLDL.
• Apo E is rich in arginine and has four subgroups.

Transport of Lipids

• Chylomicrons are responsible for the transport of all dietary lipids into the circulation.
• Chylomicron production increases with absorbed triacylglycerol load.
• Most plasma VLDL originates from the liver, transporting TAG from the liver to extrahepatic tissues.

Metabolism of Chylomicrons and VLDL

• Chylomicrons and VLDL are rapidly catabolized, with a half-life of less than one hour.
• Triacylglycerols of chylomicrons and VLDL are hydrolyzed by lipoprotein lipase.
• LPL is located in the endothelium in the wall of blood capillaries and is found in peripheral tissues.
• Hepatic lipase is involved in chylomicron residues and HDL metabolism.

LDL

• LDL is the lipoprotein that carries the most cholesterol in the circulation, carrying cholesterol from the liver to peripheral tissues.
• LDL is synthesized from VLDL residues, with a half-life of about two days.
• LDL is metabolized via the LDL receptor, with 70% degraded in the liver and 30% in extrahepatic tissues.

Atherosclerosis

• LDLs penetrate vascular walls, deposit in the intima, and with time are damaged by oxidation.
• Oxidized LDLs attract the attention of macrophages, which ingest the LDL, leading to the formation of foam cells and atherosclerotic plaques.

HDL

• HDL is a lipoprotein made by the liver and small intestine, collecting excess cholesterol from cells.
• HDL is a reservoir of apo C and apo E.
• HDL accepts unesterified cholesterol from other lipoprotein particles and cell membranes, which is immediately esterified by the plasma enzyme LCAT.

Metabolism of HDL

• LCAT esterifies cholesterol taken up by HDL.
• Phosphotidylcholine cholesterol acyltransferase (PCAT) is involved in the synthesis of HDL.

Normal Values for Blood Lipoproteins

• HDL > 45 mg/dl
• LDL < 130 mg/dl
• Triglycerides 35-160 mg/dl
• Cholesterol < 200 mg/dl