Lipoproteins and Their Metabolism

Lipoproteins, Metabolism & Diseases

• The lecture covers lipoproteins, their metabolism, and associated diseases.
• The date of the presentation was October 10-11, 2024.
• Four methods exist for isolating, separating, and characterizing lipoproteins: analytical centrifugation, preparative centrifugation, electrophoresis, and precipitation techniques.

Classification of Lipoproteins

• Lipoproteins are classified based on their density.
• Chylomicrons, VLDL, LDL, and HDL are different types of lipoproteins.

Lipoprotein Structure

• Lipoproteins consist of a core containing triglycerides and cholesterol esters, surrounded by a shell of phospholipids, free cholesterol, and apoproteins.
• Apoproteins are proteins that are part of the lipoprotein structure and are essential for their function.

Chylomicrons

• Chylomicrons are primarily composed of triglycerides, with smaller amounts of cholesterol, phospholipids, and apoproteins.
• Apoproteins associated with chylomicrons include Apo B-48, Apo A-I, Apo A-II, Apo C-I, Apo C-II, Apo C-III, and small amounts of Apo B-100, Apo E-II, Apo E-III, and Apo E-IV.

Very Low Density Lipoproteins (VLDL)

• VLDL contains triglycerides, phospholipids, cholesterol, and apoproteins.
• The proportion of triglycerides in VLDL varies with the size of the particle; larger particles contain a greater proportion of triglycerides, while smaller particles contain a greater proportion of other lipids and apoproteins.
• Partially degraded VLDL, termed remnant lipoproteins, are rich in cholesterol and can contribute to atherosclerosis.

Low Density Lipoproteins (LDL)

• LDL is primarily composed of cholesterol.
• About 80% of LDL is lipid and 20% protein.
• LDL constitutes 40% to 50% of plasma lipoprotein mass.
• LDL is a major carrier of cholesterol and plays a role in atherosclerotic disease.
• ApoB-100 is the major apoprotein of LDL and plays a critical role in LDL metabolism. 

High Density Lipoproteins (HDL)

• HDL contains a higher proportion of protein (approximately 50%) compared to other lipids (approximately 50%).
• HDL is the smallest and densest lipoprotein.
• HDL's major lipid is phospholipid, although HDL cholesterol is of interest because it plays a key role in reverse cholesterol transport.
• Phosphatidylcholine (lecithin) is the most prevalent phospholipid in HDL.

Lipoprotein Metabolism

• The lipoprotein transport system carries hydrophobic core lipids like triglycerides and cholesterol esters.
• Circulating lipoproteins undergo continuous modification by enzymes and proteins in the metabolic cascade.
• Lipoprotein metabolism can be classified into exogenous (diet-derived fats), endogenous (liver-synthesized fats), and reverse cholesterol pathways.

Chylomicron Metabolism

• Chylomicrons transport dietary triglycerides to peripheral tissues.
• Lipoprotein lipase (LPL) breaks down triglycerides in chylomicrons for use by cells.
• Chylomicron remnants are cleared from the bloodstream by the liver.

Reverse Cholesterol Transport

• Reverse cholesterol transport involves the transfer of cholesterol from peripheral tissues to the liver, which is crucial for maintaining cholesterol homeostasis and preventing atherosclerosis.
• HDL plays a central role in this process to remove cholesterol from plaques within blood vessels.

Hyperlipidemia

• Hyperlipidemia is a condition involving elevated levels of plasma lipids (cholesterol and triglycerides).
• Hyperlipidemia can be an indicator of hyperlipoproteinemia and can lead to atherosclerosis and cardiovascular disease (CVD) if left untreated.
• Often, hyperlipidemia is asymptomatic.
• Specific symptoms, e.g., abdominal pain, pancreatitis, xanthomas, and corneal arcus, might occasionally be observed.

Coronary Artery Disease (CAD)

• Coronary artery disease is a common type of heart disease resulting from atherosclerosis.
• Atherosclerosis, in turn, is caused by the accumulation of fatty deposits in artery walls, leading to the formation of fibrous tissue.
• Factors contributing to CAD include age, gender, family history, ethnicity, genetics, previous history of CVD, blood pressure, total and HDL cholesterol, smoking, diet, exercise, stress, income, social deprivation, and environment.

NCEP ATP III Guidelines

• Guidelines from The National Cholesterol Education Program Adult Treatment Panel III (ATP III) aim to standardize the approach to the diagnosis, treatment, and monitoring of individuals at high risk for coronary heart disease.
• The guideline recommends a complete lipoprotein profile as an initial test.
• Optimal LDL cholesterol is below 100 mg/dL, while HDL cholesterol below 40 mg/dL is considered low.
• Triglycerides should be less than 150 mg/dL. Therapeutic goals based on risk factor vary, but overall objectives are focused on reducing risk and promoting optimal lipid profiles. 
• There are various classification criteria for optimal lipoprotein levels.

Metabolic Syndrome (MS)

• Metabolic syndrome is a cluster of interrelated metabolic risk factors that drive atherosclerotic cardiovascular disease (CVD).
• Conditions like abdominal obesity and insulin resistance are associated with increased risk of MS.

Atherogenic Dyslipidemia

• Atherogenic dyslipidemia is a combination of lipoprotein abnormalities that contribute to atherosclerosis. Elevated plasma triglycerides, increased small LDL particles, and decreased HDL cholesterol are characteristics of this condition.

Clinical Implications of Hyperlipidemia

• Hyperlipidemia is frequently asymptomatic.
• Long-term elevated lipid levels can lead to the development of atherosclerosis and cardiovascular disease.
• Occasional symptoms might be observed depending on the type and severity of the condition.

SR-B1

• SR-B1 is a receptor involved in the uptake of HDL-derived cholesteryl esters into cells and tissues.
• SR-B1 also facilitates the efflux of cholesterol from peripheral tissues and macrophages to the liver.

Pathological Conditions and Classification

• Various types of hyperlipoproteinemia have been identified. This information is categorized in multiple types (e.g., I, II-A, II-B, III, IV, V). This categorization is primarily based on abnormal lipoproteins and includes criteria for differentiating into primary (hereditary) vs. secondary (acquired) forms. Different abnormal patterns are important to understand the underlying cause of the lipid abnormalities.

This quiz explores the structure, classification, and metabolism of lipoproteins, as well as the diseases associated with their dysfunction. It covers methods for isolation and characterization, focusing on chylomicrons, VLDL, LDL, and HDL. Test your knowledge of lipoproteins and their role in human health.