Lipids and Lipoproteins

Lipids and Lipoproteins

Topic Outline

Lipid Chemistry

Fatty Acids

Triglycerides

Phospholipids

Cholesterol

Topic Outline

General Lipoprotein Structure

Chylomicrons

Very Low Density Lipoproteins (VLDL)

Low-Density Lipoproteins (LDL)

Lipoprotein (a)

High-Density Lipoproteins (HDL)

Lipid Disorders

Objectives:

After the discussion, students will be able to

identify the principal lipids found in cells.

Students will be able to describe some

lipoprotein particles.

Also, they will be able to identify some of

the lipid disorders.

Oil Tanker

I. Lipid Chemistry

Lipids

Commonly referred to as fats

Rich source of energy

Composed of mostly carbon-hydrogen bonds

Principal lipids found in cells:

triglycerides, phospholipids, cholesterol, and

cholesteryl esters

Fatty Acids

Simple linear chains of C-H bonds

Attached to glycerol backbone of triglycerides

and phospholipids by an ester bond

Variable in length:

Short chain (4-6 carbon atoms)

Medium chain (8-12 carbon atoms)

Long-chain (more than 12 carbon atoms)

Fatty Acids

Classified as to number of C=C double bonds:

Saturated – no double bonds

Monounsaturated – one double bond

Polyunsaturated – two or more double bonds

The C=C double bonds of unsaturated fatty

acids are typically arranged in cis form.

Structures of Fatty Acid

Triglycerides

Contain three fatty acid molecules attached to

one molecule of glycerol by ester bonds.

Triglycerides containing saturated fatty acid,

do not have bends in their structure.

Triglyceride containing cis unsaturated fatty

acids forms oil at room temperature.

Triglycerides

Triglycerides do not have charged groups,

making it very hydrophobic and water

insoluble. It is classified as neutral lipid.

Phospholipids

Similar in structure to triglycerides except that

they only have two esterified fatty acids

and the third position on the glycerol

backbone contains a phospholipid head group.

The two fatty acids in phospholipids are

normally 14 to 24 C atoms, with one fatty acid

commonly saturated and the other unsaturated.

Phospholipids

They are amphipathic.

Types of phospholipid head groups:

Choline

Inositol serine

Ethanolamine

Phospholipids are named based on the type

of phospholipid head group present.

Structure of a Phospholipid

Cholesterol

Unsaturated steroid alcohol containing four

rings (A, B, C, and D)

Has single C-H side chain tail

Only hydrophilic part is the hydroxyl group

in the A-ring.

Also an amphipathic lipid

Structure of cholesterol

Cholesteryl Ester

Esterified form of cholesterol

With the hydroxyl group conjugated by an

ester bond to a fatty acid.

No polar groups – hydrophobic

Synthesized by animals

Cholic acid and Chenodeoxycholic

acid

Converted cholesterol in the liver to

primary bile acids

Promote fat absorption in the intestine

II. General Lipoprotein Structure

Lipoproteins

Spherical in shape

Composed of both lipids and proteins,

called apolipoproteins

Main role of lipoproteins is the delivery of

fuel to peripheral cells.

Lipoprotein

Various lipoprotein particles were originally

separated by ultracentrifugation into

different density fractions (chylomicrons

[chylos], VLDL, LDL, HDL)

Apolipoproteins

Located on the surface of lipoprotein particles

Help maintain the structural integrity of lipoproteins

Ligands: cell receptor

Activators and inhibitors: enzymes

Contain structural motif called amphipathic helix – ability to bind to lipids

Apolipoprotein (apo) A-I

Major protein on HDL

Used as index of the amount of the antiatherogenic HDL present in plasma.

Apo B

Principal protein on LDL, VLDL and chylos

Apo B-100: LDL and VLDL

Apo B-48: chylomicrons

Chylomicrons

Apo B-48

Least dense

Reflect light and turbidity of postprandial

plasma

Produced by intestine

Delivery of dietary lipids to hepatic and

peripheral cells

Very Low Density Lipoproteins (VLDL)

Apo B-100

Produced by the liver

Rich in triglycerides

Transfer triglycerides from the liver to

peripheral tissue

Smaller and less buoyant

Low-Density Lipoprotein (LDL)

Apo B-100

Cholesterol-rich

Readily taken up by cells via LDL

receptor

Lipoprotein (a)

LDL-like particles

Apo (a) linked to Apo B-100 by disulfide

bond

heterogenous

High-Density Lipoprotein (HDL)

Smallest and most dense

Synthesized by liver and intestine

Disk-shaped or spherical

Highly heterogenous

Discoidal HDL – newly secreted HDL

Reverse cholesterol transport – ability of

HDL to remove cholesterol from cells

III. Lipid Disorders

Dyslipidemia

Abnormal lipid concentrations

Associated with Coronary Heart Disease

Arteriosclerosis

Thickening and hardening of arterial walls

in the arteries

Form of esterified cholesterol in artery

walls

Peripheral Vascular Disease (PVD)

Coronary Artery Disease (CAD)

Cerebrovascular Disease (CVD)

Hyperlipoproteinemia

Diseases associated with elevated

lipoprotein levels

Subdivided into:

Hypercholesterolemia

Hypertriglyceridemia

Combined hyperlipidemia

Hypercholesterolemia

Lipid abnormality most closely linked to

heart disease

Elevated cholesterol level

Familial Hypercholesterolemia (FH) -

genetic

Hypertriglyceridemia

Elevated triglyceride level

Familial Hypertriglyceridemia – genetic

abnormality, hormonal abnormality

Combined Hyperlipoproteinemia

Elevated levels of serum total cholesterol

and triglycerides

Familial combined hyperlipoproteinemia

Lipoprotein (a) Elevation

Elevation in serum concentration of Lp(a)

Elevations of LDL

Hypolipoproteinemia

Low levels of lipoprotein

Two forms:

Hypoalphalipoproteinemia

Hypobetalipoproteinemia

Hypoalphaipoproteinemia

Isolated decrease in circulating HDL

Treatment with Niacin

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