Lipids and Lipoproteins Overview

Lipids and Lipoproteins

• Lipids are chemically diverse compounds characterized by hydrophobicity (low water solubility)

• Soluble in organic solvents like acetone and chloroform

• Serve significant biological roles, including energy storage, structural components of cell membranes, hormone cofactors, and more

• Fats, oils, and waxes are lipids

Biological Roles of Lipids

• Energy storage
• Structural components of cell membranes
• Enzyme cofactors
• Hormones
• Membrane anchors for proteins
• Signaling messengers
• Electron carriers
• Emulsifier agents (digestion and blood transport)
• Solvents for vitamins A, D, E, and K

Classification of Lipids (Bloor's)

• Simple Lipids: Natural fats (triglycerides), waxes (true waxes, cholesterol esters, vitamins A & D esters)
• Compound Lipids: Phospholipids, Glycolipids, Sulpholipids, Aminolipids (Proteolipids), Lipoprotein

Derived Lipids

• Products of hydrolysis of simple and compound lipids
• Fatty acids
• Mono- and diglycerides
• Alcohols (straight chain alcohols, water-insoluble, from wax hydrolysis)
• Cholesterol and steroids (including Vitamin D)
• Glycerol
• Some carotenoids
• Vitamins E and K
• Carotenoids
• Squalene

Classification of Plasma Lipids

• Fatty acids
• Triglycerides
• Phospholipids
• Cholesterol

Fatty Acids

• Highly reduced linear hydrocarbon chains with a carboxylic group at the end (CH3(CH2)nCOO- where n=4 to 36C)
• Can be saturated or unsaturated

Saturated Fatty Acids

• Contain only single bonds in the hydrocarbon chain
• Saturated with hydrogens, linear
• Examples: Lauric acid (C12), Palmitic acid (16 carbons), and Stearic acid (18 carbons)

Unsaturated Fatty Acids

• Contain one or more double bonds in the hydrocarbon chain
• Examples: Palmitoleic acid (16:1), polyunsaturated fatty acids which have more than 1 double bond

Triglycerides

• Esters between glycerol and three fatty acids
• Major components of human diet
• Function: energy storage for cells (accumulate as oily droplets)
• Storage and transport (does not require carrying large amounts of water)
• Insulation (hydrophobic and low conductivity)

Phospholipids

• Complex lipids resembling triglycerides but with a phosphate and nitrogenous base
• Functions: energy storage for cells, surfactants (like sphingomyelin), water insulation (hydrophobic), storage and transport (does not require large amounts of water), insulation, and thermal insulation

Cholesterol

• Cholesterol composition is a perhydrocyclopentanthroline ring structure
• Synthesis involves 25 separate enzyme steps, starting with Acetyl CoA
• Occurs in the blood as esters, in tissues as free form
• Functions: structural component of cell membranes, precursor for steroid hormones and bile salts, acting as a protective agent for skin (up to 300 mg per day secreted) and a source for natural biosynthesis and dietary intake

Lipoproteins

• Provide a water-soluble means to transport hydrophobic lipids
• Consist of a core of insoluble non-polar cholesterol esters and triglycerides surrounded by proteins, phospholipids, and free cholesterol (polar groups outwards)
• Synthesized in the liver or intestine
• Modified by enzymes after secretion, remnants taken up by cell surface receptors
• Regulated by the protein component (apolipoproteins)

Types of Lipoproteins

• Chylomicrons
• Very Low Density Lipoproteins (VLDL)
• Low-density lipoprotein (LDL)
• High Density Lipoproteins (HDL)

Chylomicrons

• 75-120 nm
• 81.3% Triglycerides
• 9.1% Cholesterol and Cholesterol esters, 7.1% Phospholipids, 2.5% Protein
• Contain Apolipoproteins A & B
• Apolipoproteins C & E acquired post-secretion
• Source: Intestine
• Function: Transport exogenous lipid from intestine to all cells
• Lifespan: from formation after a meal until the remnant has been removed by liver (~6 hrs)

VLDL

• 25-75 nm
• 51.8% Triglycerides, 22.2% Cholesterol & Cholesterol esters, 26.0% Phospholipids, 7.1% Protein
• Contain Apolipoproteins B, C, & E
• Source: Synthesized in the liver
• Function: Transport endogenous triglycerides. Lifespan varies as core shrinks due to triglyceride loss
• Shrinks to become LDL
• Supplies nutrients between meals

LDL

• ~22 nm
• 9.3% Triglycerides, 50.0% Cholesterol & Cholesterol esters, 20.0% Phospholipids, 20.7% Protein
• Contain Apolipoprotein B
• Source: Metabolism of VLDL via IDL
• Function: Energy (Triglycerides into fatty acids and glycerol), cell replication (apoproteins into amino acids), cell integrity (cholesterol and cholesterol esters to repair/maintain membranes), steroid hormone production (cholesterol to produce cortisol, testosterone, oestrogen, androgens), and cellular uptake (number of Apo B receptors influence uptake)

HDL

• 7-10 nm
• 8.1% Triglycerides, 20.0% Cholesterol & Cholesterol esters, 21.9% Phospholipids, 50% Protein
• Contain Apolipoproteins A, C, & E
• Sources: Intestine and Liver
• Cellular sites via action of LCAT and ApoA1 on liver precursors
• Function: Transports cholesterol to the liver, liver produces disc containing phospholipids, apolipoproteins and minimal cholesterol and triglycerides, LCAT and Apo A1 esterifies cholesterol and internalizes it
• Once full -> Liver

Apolipoproteins

• Essential protein components of lipoproteins that determine the function and fate of lipoproteins
• Many different types (A-E). Each plays a role (e.g., A-1 in HDL, B in LDL)

Lipid Disorders (Hyperlipidaemias)

• Dyslipidemia: increased LDL + reduced HDL
• Hypertriglyceridaemia: increased TG (>150mg/dL)
• Hypercholesterolaemia: total cholesterol > 200mg/dL, increased LDL & VLDL, reduced HDL
• Hyperlipidaemia: increased LDL + TG
• Mixed hyperlipidaemia

Causes of Lipid Disorders (Inherited and Acquired)

• Inherited/Familiar: Genetic disorders
• Acquired disorders: Diabetes, hypothyroidism, nephrotic syndrome, medications (beta-blockers, estrogen, thiazides), weight, and diet

Fredrickson Classification

• System used to classify inherited hyperlipidaemias based on plasma lipoprotein phenotypes.

Clinical Manifestations of Hyperlipidemia

• Accumulation of lipids in tissues (arterial walls, subcutaneous tissues, tendons, cornea) leading to further issues (atherosclerosis, xanthomatosis, cornea arcus)

Accumulation of Lipids in Tissues

• Arterial Walls: most common, cholesterol accumulation, cellular proliferation, and fibrous tissue form plaques
• Subcutaneous Tissues (Xanthomatosis): nature of lipid fraction is key, eruptive, tuberous, xanthoma
• Tendons: cholesterol deposit in macrophages cause tendon thickening
• Cornea (Cornea Arcus): associated high LDL cholesterol, common grey, white, or yellowish deposits in the peripheral cornea. Typically seen in older patients.

Hypertriglyceridaemia

• Caused by elevated chylomicrons, VLDL, or both
• Primary: familial and autosomal dominant, hepatic triglyceride overproduction
• Secondary: secondary to other disorders (diabetes, hypothyroidism, nephrotic syndrome, alcohol intake)

Hypercholesterolaemia

• Primary (familial): deficiency of LDL receptors
• Secondary: hypothyroidism, diabetes, nephrotic syndrome, cholestasis

Mixed Hyperlipidaemia

• Elevated triglycerides and cholesterol
• Often caused by poorly controlled diabetes, severe hypothyroidism, or nephrotic syndrome, familial combined hyperlipidemia

Hypolipidaemias

• Rare disorders
• Associated with reduced plasma lipid levels, but still tissue accumulation
• Inherited disorders
  • Tangier disease (abnormal Apo A-1, accumulation in reticuloendothelial system)
  • Abetalipoproteinemia (Apo B deficiency)
  • Lecithin-cholesterol acyltransferase (LCAT) deficiency

Lipid Profiling

• Total Cholesterol, HDL Cholesterol, Triglycerides, LDL Triglycerides (measured), Total Cholesterol: HDL Cholesterol Ratio (calculated)

Friedewald Formula

• Estimate LDL cholesterol without ultracentrifugation
• LDL cholesterol = total cholesterol – HDL cholesterol – VLDL cholesterol
• Reasonably accurate below 4.5mmol/L triglycerides, but unreliable with high triglycerides
• VLDL cholesterol measured directly (after ultracentrifugation)

NICE Guidelines

• Optimize management of modifiable risk factors before lipid modification therapy for primary prevention:
• Smoking status, alcohol consumption, level of exercise, blood pressure, body mass index

Explore the diverse world of lipids and lipoproteins, highlighting their unique chemical properties and essential biological roles. This quiz covers classification, functions, and the significance of lipids in energy storage and cellular structures.