Lipid Chemistry

Feature	Linoleic Acid	α-Linolenic Acid	Arachidonic Acid
Notation	18:2	18:3	20:4
Omega Family	ω-6	ω-3	ω-6
Essentiality	Essential	Essential	Conditionally Essential
Major Function	Cell membranes, eicosanoids	Brain and heart health	Eicosanoid synthesis

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Triglycerides

• Triacylglycerols (TAGs), also known as triglycerides, triacylglycerides, or neutral fats, are the most abundant lipids in the human body and the major storage form of energy.
• They constitute about 95% of the lipids present in dietary fats and oils.
• Triacylglycerols are stored mainly in adipose tissue and serve as an energy reserve that can be utilized during fasting, starvation, or increased physical activity.

Definition

• Triacylglycerols are esters formed by the reaction of one molecule of glycerol with three molecules of fatty acids.
• Since all three hydroxyl groups of glycerol are esterified, triglycerides are called triacylglycerols.

Structure of Triacylglycerols

A triglyceride molecule consists of:

• One glycerol molecule (3-carbon alcohol)
• Three fatty acid molecules
• Three ester bonds

General Structure:

Glycerol + 3 Fatty Acids → Triacylglycerol + 3 H₂O

The ester linkage is formed between the hydroxyl group of glycerol and the carboxyl group of fatty acids.

Types of Triacylglycerols

1. Simple Triacylglycerols

• When all three fatty acids attached to glycerol are identical.

Examples:

• Tripalmitin (3 molecules of palmitic acid)
• Tristearin (3 molecules of stearic acid)
• Triolein (3 molecules of oleic acid)

2. Mixed Triacylglycerols

• When two or three different fatty acids are attached to glycerol.

Example:

• Palmito-oleo-stearin

Most naturally occurring fats and oils are mixed triglycerides.

Physical Properties of Triacylglycerols

1. Insolubility in Water

• Triglycerides are nonpolar molecules.
• Insoluble in water.
• Soluble in organic solvents such as ether, chloroform, benzene, and acetone.

2. State at Room Temperature

• Rich in saturated fatty acids → Solid (Fats)
• Rich in unsaturated fatty acids → Liquid (Oils)

Examples

Fats

• Butter
• Ghee
• Animal fat

Oils

• Olive oil
• Sunflower oil
• Groundnut oil

3. Density

• Less dense than water.
• Therefore, fats float on water.

Functions of Triacylglycerols

1. Major Energy Reserve

• Principal storage form of energy in the body.
• Stored in adipose tissue.
• Provide approximately 9 kcal/g.

2. Thermal Insulation

• Subcutaneous fat reduces heat loss.
• Helps maintain body temperature.

3. Mechanical Protection

• Cushions and protects vital organs.
• Acts as a shock absorber around kidneys, heart, and eyeballs.

4. Source of Essential Fatty Acids

• Supply essential fatty acids required for normal growth and development.

5. Vehicle for Fat-Soluble Vitamins

• Aid in absorption and transport of vitamins A, D, E, and K.

6. Source of Metabolic Water

• Oxidation of triglycerides produces water and energy.

Digestion and Absorption

• Digestion begins minimally in the stomach.
• Major digestion occurs in the small intestine.
• Pancreatic lipase hydrolyzes triglycerides into:
  • Monoglycerides
  • Free fatty acids
  • Glycerol

These products are absorbed by intestinal mucosal cells and reassembled into triglycerides.

Storage of Triacylglycerols

Triglycerides are stored mainly in:

• Adipose tissue
• Liver (small amount)
• Skeletal muscle

Adipose tissue acts as the body’s energy reservoir.

Mobilization of Stored Fat

During fasting, starvation, or exercise:

• Hormone-sensitive lipase becomes activated.
• Triglycerides are broken down into:
  • Free fatty acids
  • Glycerol

This process is called lipolysis.

The released fatty acids are transported to tissues for energy production.

Clinical Significance

Hypertriglyceridemia

Elevated triglyceride levels in blood may occur in:

• Obesity
• Diabetes mellitus
• Hypothyroidism
• Nephrotic syndrome
• Excessive alcohol consumption

Complications:

• Acute pancreatitis
• Atherosclerosis
• Cardiovascular disease

Obesity

• Excess calories are stored as triglycerides in adipose tissue, leading to increased body fat and obesity.

Fatty Liver

• Excess accumulation of triglycerides in liver cells results in fatty liver (hepatic steatosis).

Common causes include:

• Alcoholism
• Obesity
• Diabetes mellitus
• Malnutrition

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Phospholipids

• Phospholipids are one of the most important classes of lipids found in living organisms.
• They are complex lipids containing fatty acids, an alcohol, phosphoric acid, and a nitrogenous base or another substituent.
• Phospholipids are present in every cell of the body and are the principal structural components of biological membranes.
• Because phospholipids contain both hydrophilic (water-loving) and hydrophobic (water-repelling) portions, they possess unique physical and biological properties that enable them to form cell membranes.
• Approximately 40–50% of the lipids present in most cell membranes are phospholipids.

Definition

Phospholipids are complex lipids that contain:

• Fatty acids
• Alcohol (Glycerol or Sphingosine)
• Phosphoric acid
• Nitrogenous base or other substituent

On hydrolysis, they yield:

• Fatty acids
• Alcohol
• Phosphoric acid
• Nitrogenous compound

General Structure of Phospholipids

A typical phospholipid molecule consists of:

Hydrophilic Head

Contains:

• Phosphate group
• Nitrogenous base

Hydrophobic Tail

Contains:

• Two fatty acid chains

This dual nature makes phospholipids amphipathic molecules.

Amphipathic Nature of Phospholipids

The amphipathic nature is the most important property of phospholipids.

Hydrophilic Portion

• Phosphate group
• Polar
• Water soluble

Hydrophobic Portion

• Fatty acid chains
• Nonpolar
• Water insoluble

Because of this property, phospholipids spontaneously arrange themselves into bilayers when placed in water.

This forms the basis of:

• Cell membranes
• Organelle membranes
• Liposomes
• Micelles

Classification of Phospholipids

Phospholipids are classified into:

1. Glycerophospholipids

• Contain glycerol as the alcohol.

2. Sphingophospholipids

• Contain sphingosine as the alcohol.

1. Glycerophospholipids

These are the most abundant phospholipids in humans.

Structure

Contain:

• Glycerol
• Two fatty acids
• Phosphoric acid
• Nitrogenous base

The parent compound is Phosphatidic Acid.

Phosphatidic Acid

Importance

• Simplest phospholipid
• Precursor of all glycerophospholipids
• Intermediate in triglyceride synthesis

Important Glycerophospholipids

A. Lecithin (Phosphatidylcholine)

• Lecithin is the most abundant phospholipid in animal tissues.

Distribution

Found in:

• Cell membranes
• Liver
• Brain
• Egg yolk
• Soybeans
• Lipoproteins

Functions

• Structural Function – Major constituent of biological membranes.
• Lipid Transport – Important component of plasma lipoproteins.
• Bile Formation – Keeps cholesterol dissolved in bile.
• Lung Surfactant – Dipalmitoyl phosphatidylcholine (DPPC) is the major pulmonary surfactant.

Clinical Importance

Respiratory Distress Syndrome (RDS)

• Premature infants may lack sufficient surfactant.

Results in:

• Alveolar collapse
• Difficulty in breathing
• Respiratory failure

Lecithin/Sphingomyelin (L/S) ratio in amniotic fluid is used to assess fetal lung maturity.

Normal L/S ratio > 2

B. Cephalin (Phosphatidylethanolamine)

• Contains ethanolamine as the nitrogenous base.

Functions

• Component of cell membranes
• Important in blood coagulation
• Present in nervous tissue
• Maintains membrane stability

C. Phosphatidylserine

• Contains serine as the nitrogenous base.

Functions

• Cell signaling
• Apoptosis regulation
• Membrane stability
• Neuronal function

D. Phosphatidylinositol

• Contains inositol instead of a nitrogenous base.

Functions

• Signal transduction
• Formation of second messengers

Important second messengers:

• IP3 (Inositol triphosphate)
• DAG (Diacylglycerol)

These regulate:

• Hormonal responses
• Calcium release
• Cell growth

E. Cardiolipin

• A unique phospholipid present mainly in mitochondria.

Distribution

• Inner mitochondrial membrane

Functions

• Essential for oxidative phosphorylation
• Supports electron transport chain
• Maintains mitochondrial membrane integrity

Clinical Importance

Cardiolipin antigen is used in:

• VDRL test
• RPR test

for the diagnosis of syphilis.

2. Sphingophospholipids

• These phospholipids contain sphingosine instead of glycerol.

The most important member is:

Sphingomyelin

Structure

Contains:

• Sphingosine
• Fatty acid
• Phosphoric acid
• Choline

Distribution

Abundant in:

• Brain
• Nervous tissue
• Myelin sheath
• Cell membranes

Functions

• Formation of Myelin Sheath – Protects nerve fibers.
• Electrical Insulation – Allows rapid conduction of nerve impulses.
• Membrane Structure – Contributes to membrane stability.

Clinical Importance

Niemann-Pick Disease

• Caused by deficiency of sphingomyelinase enzyme.

Results in:

• Accumulation of sphingomyelin
• Hepatosplenomegaly
• Neurological abnormalities
• Developmental delay

Functions of Phospholipids

1. Structural Components of Cell Membranes

Phospholipids are the principal constituents of:

• Plasma membrane
• Nuclear membrane
• Mitochondrial membrane
• Endoplasmic reticulum

2. Formation of Lipid Bilayer

• In aqueous environments phospholipids arrange into a bilayer.
• This bilayer forms the framework of biological membranes.

3. Lung Surfactant Function

• Dipalmitoyl phosphatidylcholine reduces surface tension inside alveoli.

Prevents:

• Alveolar collapse
• Atelectasis

4. Lipid Transport

Phospholipids are essential components of:

• HDL
• LDL
• VLDL
• Chylomicrons

They help transport lipids through blood.

5. Cell Signaling

Phosphatidylinositol participates in:

• Hormone action
• Signal transduction
• Intracellular communication

6. Blood Coagulation

Cephalin functions as platelet factor.

Important in:

• Clot formation
• Hemostasis

7. Emulsification of Lipids

Lecithin acts as a natural emulsifying agent.

Facilitates:

• Digestion of fats
• Absorption of lipids

8. Nerve Impulse Conduction

Sphingomyelin forms the myelin sheath.

Helps:

• Rapid nerve conduction
• Protection of neurons

Clinical Significance of Phospholipids

Respiratory Distress Syndrome (RDS)

Cause:

• Surfactant deficiency

Key molecule:

• Dipalmitoyl lecithin

Niemann-Pick Disease

Cause:

• Sphingomyelinase deficiency

Accumulated lipid:

• Sphingomyelin

Atherosclerosis

Abnormal phospholipid metabolism contributes to:

• Endothelial injury
• Plaque formation

Gallstone Formation

Reduced lecithin concentration in bile leads to:

• Cholesterol precipitation
• Gallstone formation

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Glycolipids

• Glycolipids are a group of complex lipids that contain one or more carbohydrate residues attached to a lipid molecule.
• They are important constituents of cell membranes, particularly in nervous tissue. Unlike phospholipids, glycolipids do not contain phosphoric acid.
• Glycolipids are especially abundant in the brain, spinal cord, peripheral nerves, and the outer surface of plasma membranes, where they play vital roles in cell recognition, communication, and membrane stability.

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Definition

Glycolipids are complex lipids that contain:

• Fatty acid
• Sphingosine
• Carbohydrate residue(s)

but lack phosphoric acid.

On hydrolysis, glycolipids yield:

• Fatty acid
• Sphingosine
• One or more sugar molecules

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General Structure of Glycolipids

A typical glycolipid consists of:

Lipid Portion

• Sphingosine
• Fatty acid

Together they form Ceramide.

Carbohydrate Portion

• Glucose
• Galactose
• Oligosaccharides
• Sialic acid

Thus:

Ceramide + Carbohydrate = Glycolipid

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Distribution of Glycolipids

Glycolipids are found mainly in:

• Brain
• Nervous tissue
• Myelin sheath
• Erythrocyte membrane
• Cell membranes

They are concentrated on the outer surface of plasma membranes.

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Classification of Glycolipids

Glycolipids are classified according to the carbohydrate attached to ceramide.

1. Cerebrosides

• These are the simplest glycolipids.

Structure

• Ceramide + Single Sugar

The sugar may be:

• Glucose
• Galactose

Types

Glucocerebroside

• Contains glucose.

Galactocerebroside

• Contains galactose.

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Distribution

• Brain
• Myelin sheath
• Nervous tissue

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Functions

• Structural component of cell membranes
• Formation of myelin sheath
• Insulation of nerve fibers

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2. Sulfatides

• Sulfatides are sulfated cerebrosides.

Structure

• Ceramide + Galactose + Sulfate

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Distribution

• White matter of brain
• Myelin sheath
• Nervous tissue

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Functions

• Stabilization of myelin membrane
• Nerve conduction

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3. Globosides

• Globosides contain two or more sugar residues.

Structure

• Ceramide + Oligosaccharides

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Distribution

• Cell membranes
• Red blood cells
• Various tissues

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Functions

• Cell recognition
• Cell adhesion
• Blood group antigen expression

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4. Gangliosides

• Gangliosides are the most complex glycolipids.

Structure

• Ceramide + Oligosaccharides + Sialic Acid (NANA)

NANA = N-Acetylneuraminic Acid

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Distribution

Highly concentrated in:

• Brain
• Gray matter
• Nerve endings
• Synaptic membranes

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Functions

• Cell Recognition – Act as receptors on cell surfaces.
• Signal Transmission – Participate in nerve impulse transmission.

Receptor Function

Serve as receptors for:

• Hormones
• Toxins
• Viruses

Cellular Communication

Essential for communication between cells.

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Functions of Glycolipids

1. Structural Components of Cell Membranes

• Glycolipids contribute to membrane stability and integrity.

2. Cell Recognition

• They act as surface markers that allow cells to recognize one another.

3. Receptor Functions

• Many glycolipids function as receptors for:
• Hormones
• Bacterial toxins
• Viruses

4. Blood Group Antigens

• ABO blood group antigens are present on membrane glycolipids.

5. Nervous System Function

Important components of:

• Brain tissue
• Myelin sheath
• Synaptic membranes

6. Cell Adhesion and Communication

• Help cells interact with neighboring cells.

7. Protection of Cell Surface

• Form part of the glycocalyx that protects cells from mechanical and chemical injury.

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Clinical Significance of Glycolipids

Abnormal metabolism of glycolipids causes a group of inherited disorders called Sphingolipidoses.

1. Gaucher Disease

Enzyme Deficiency

• β-Glucocerebrosidase

Accumulated Lipid

• Glucocerebroside

Clinical Features

• Hepatosplenomegaly
• Bone pain
• Anemia
• Thrombocytopenia

Most common lysosomal storage disease.

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2. Tay-Sachs Disease

Enzyme Deficiency

• Hexosaminidase A

Accumulated Lipid

• GM₂ Ganglioside

Clinical Features

• Progressive neurodegeneration
• Blindness
• Developmental delay
• Cherry-red spot in retina

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3. Krabbe Disease

Enzyme Deficiency

• Galactocerebrosidase

Accumulated Lipid

• Galactocerebroside

Clinical Features

• Severe neurological deterioration
• Mental retardation
• Peripheral neuropathy

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4. Metachromatic Leukodystrophy

Enzyme Deficiency

• Arylsulfatase A

Accumulated Lipid

• Sulfatides

Clinical Features

• Demyelination
• Muscle weakness
• Neurological dysfunction

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Comparison of Major Glycolipids

Glycolipid	Carbohydrate Component	Major Location
Cerebrosides	Single sugar	Brain and myelin
Sulfatides	Sulfated sugar	White matter
Globosides	Multiple sugars	Cell membranes
Gangliosides	Oligosaccharides + Sialic acid	Brain and nerve endings

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Summary Table of Glycolipid Storage Diseases

Disease	Enzyme Deficiency	Accumulated Lipid
Gaucher Disease	β-Glucocerebrosidase	Glucocerebroside
Tay-Sachs Disease	Hexosaminidase A	GM₂ Ganglioside
Krabbe Disease	Galactocerebrosidase	Galactocerebroside
Metachromatic Leukodystrophy	Arylsulfatase A	Sulfatides

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Cholesterol

• Cholesterol is the most important sterol found in animal tissues and is one of the most extensively studied lipids in biochemistry.
• Although cholesterol is often associated with heart disease, it is actually an essential component of the human body and is required for normal cellular and physiological functions.
• Cholesterol is present in every cell membrane and serves as a precursor for several biologically important compounds, including steroid hormones, bile acids, and vitamin D.
• Approximately 1–2 g of cholesterol is present in the adult human body, with high concentrations found in the brain, liver, spinal cord, adrenal glands, and cell membranes.

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Definition

Cholesterol is a 27-carbon monohydric alcohol belonging to the steroid family of lipids.

It contains:

• Four fused hydrocarbon rings (steroid nucleus)
• One hydroxyl (-OH) group
• A hydrocarbon side chain

Because it contains both lipid and alcohol characteristics, cholesterol is classified as a sterol.

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Structure of Cholesterol

• Structural Features

Cholesterol contains:

• Cyclopentanoperhydrophenanthrene nucleus
• Three six-membered rings
• One five-membered ring
• Hydroxyl group at carbon-3
• Double bond between carbon-5 and carbon-6
• Eight-carbon side chain attached to carbon-17

Molecular Formula

• C₂₇H₄₆O

Important Property

Cholesterol is an amphipathic molecule because:

• Hydroxyl group is hydrophilic
• Steroid nucleus and side chain are hydrophobic

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Sources of Cholesterol

1. Exogenous (Dietary) Sources

• Obtained from animal foods.

Rich Sources

• Egg yolk
• Liver
• Kidney
• Meat
• Butter
• Cheese
• Whole milk
• Fish

Note

Plant foods do not contain cholesterol.

Instead, plants contain phytosterols such as:

• β-Sitosterol
• Stigmasterol

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2. Endogenous Sources

The body synthesizes cholesterol mainly in:

• Liver
• Intestinal mucosa
• Adrenal cortex
• Skin
• Gonads

The liver is the major site of cholesterol synthesis.

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Regulation of Cholesterol Synthesis

The key regulatory enzyme is:

• HMG-CoA Reductase

Activity is inhibited by:

• High intracellular cholesterol
• Statin drugs
• Glucagon

Activity is stimulated by:

• Insulin
• Low cholesterol levels

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Functions of Cholesterol

1. Structural Component of Cell Membranes

• Essential constituent of plasma membranes.
• Maintains membrane stability and fluidity.
• Regulates membrane permeability.

2. Precursor of Steroid Hormones

Cholesterol is the precursor of:

Glucocorticoids

• Cortisol

Mineralocorticoids

• Aldosterone

Sex Hormones

• Testosterone
• Estrogen
• Progesterone

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3. Formation of Bile Acids

Cholesterol is converted into:

• Cholic acid
• Chenodeoxycholic acid

Functions:

• Emulsification of fats
• Fat digestion and absorption

4. Formation of Vitamin D

In the skin:

7-Dehydrocholesterol → Vitamin D₃

under the influence of ultraviolet sunlight.

5. Formation of Lipoproteins

Cholesterol is transported in blood as a component of:

• LDL
• HDL
• VLDL
• Chylomicrons

6. Component of Nervous Tissue

Abundant in:

• Brain
• Myelin sheath
• Nerve tissue

Supports normal nerve function.

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Transport of Cholesterol

Since cholesterol is insoluble in water, it is transported through blood by lipoproteins.

LDL (Low Density Lipoprotein)

Function

• Delivers cholesterol from liver to tissues.

Known As

Bad Cholesterol

Clinical Significance

Increased LDL promotes:

• Atherosclerosis
• Coronary artery disease

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HDL (High Density Lipoprotein)

Function

• Removes cholesterol from tissues.
• Carries cholesterol back to liver.

Known As

Good Cholesterol

Clinical Significance

Protects against:

• Atherosclerosis
• Heart disease

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Hypercholesterolemia

Hypercholesterolemia refers to elevated cholesterol levels in blood.

Causes

Primary Causes

• Familial hypercholesterolemia
• Genetic defects in LDL receptors

Secondary Causes

• Diabetes mellitus
• Hypothyroidism
• Nephrotic syndrome
• Obesity
• High-fat diet

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Effects

• Atherosclerosis
• Coronary artery disease
• Stroke
• Peripheral vascular disease

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Atherosclerosis

Atherosclerosis is characterized by deposition of cholesterol-rich plaques within arterial walls.

Process

1. Endothelial injury
2. LDL accumulation
3. Oxidation of LDL
4. Foam cell formation
5. Plaque formation

Complications

• Myocardial infarction
• Stroke
• Hypertension

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Gallstones and Cholesterol

Cholesterol is normally dissolved in bile.

When cholesterol concentration exceeds its solubility:

→ Cholesterol precipitates

→ Gallstones are formed

Risk Factors

• Obesity
• Female sex
• Pregnancy
• Diabetes mellitus

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Familial Hypercholesterolemia

An inherited disorder caused by defective LDL receptors.

Features

• Markedly elevated LDL cholesterol
• Tendon xanthomas
• Premature coronary artery disease

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Hypocholesterolemia

Decreased cholesterol levels may occur in:

• Hyperthyroidism
• Malnutrition
• Severe liver disease
• Chronic infections

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Summary Table: Functions of Cholesterol

Function	Importance
Cell membrane component	Maintains membrane fluidity
Steroid hormone synthesis	Cortisol, estrogen, testosterone
Bile acid formation	Fat digestion
Vitamin D synthesis	Calcium metabolism
Lipoprotein component	Lipid transport
Nervous tissue component	Myelin formation

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Comparison of LDL and HDL

Feature	LDL	HDL
Full Form	Low Density Lipoprotein	High Density Lipoprotein
Function	Delivers cholesterol to tissues	Removes cholesterol from tissues
Nickname	Bad Cholesterol	Good Cholesterol
Effect on Heart	Increases risk	Protective
Atherosclerosis	Promotes	Prevents