1.0 protein binding lipoproteins

Lipoproteins

are biochemical assemblies that transport hydrophobic molecules (e.g. lipids) in water dominant compartments such as blood plasma + extracellular fluids.

Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids,

primarily cholesteryl esters and triglycerides.

This hydrophobic core is surrounded by a hydrophilic membrane consisting of

phospholipids

free cholesterol,

apolipoproteins

Plasma lipoproteins, found in blood plasma, are typically divided into five main classes based on

size,

lipid composition,

apolipoprotein content

apolipoprotein

serum proteins that mediate carriage of cholesterol and other lipids in the serum

these 5 main classes are

1. High Density Lipoproteins (HDL), 

2. Low Density Lipoproteins (LDL), 

3. Intermediate Density Lipoproteins (IDL), 

4. Very Low Density Lipoproteins (VLDL) and 

5. Ultra Low Density Lipoproteins (ULDL).

Because lipids, such as cholesterol and triglycerides, are insoluble in water these

lipids must be transported in association with proteins (lipoproteins) in the circulation.

Large quantities of fatty acids from meals must be transported as triglycerides

to avoid toxicity.

These lipoproteins play a key role in

• the absorption and transport of dietary lipids by the small intestine,

• in the transport of lipids from the liver to peripheral tissues,

• and the transport of lipids from peripheral tissues to the liver and intestine (reverse cholesterol transport).

A secondary function is to transport toxic foreign hydrophobic and amphipathic compounds, such as

bacterial toxins,

from areas of invasion

and infection. 

amphipathic

a molecule especially protein having both hydrophobic and hydrophobic parts

Within the peripheral vascular system, Chylomicron remnants, VLDL, IDL, and LDL are all pro-atherogenic

while HDL is anti-atherogenic.

pro-atherogenic

structures that cause cellular dysfunction in the vessel wall

these dysfunctions can include

chromic inflammation/abnormal cell growth

and procoagulant surface

cellular dysfunction ultimately lead to

stiffening or occlusion of the peripheral vascular system

Similarly to dietary lipids and toxic compounds,

drugs may rely on lipoproteins to transport through blood plasma,

these drugs will exist in bound (pharmacologically inactive) or unbound (pharmacologically active) forms in the peripheral vascular system

depending on their affinity to these plasma lipoproteins.

In cases where this interaction is reversible, a chemical equilibrium will exist between the bound and unbound states, with shifts in this equilibrium directly affecting therapeutic effects:

Lipoprotein + drug ⇌ Lipoprotein-drug complex

A drug's half-life is directly affected by the drugs affinity to lipoprotein binding and the shift in its equilibrium.

Bound drugs may act as a reservoir or depot, which from which the drug is slowly released as the unbound form

As the unbound form is metabolized and/or excreted from the body,

the bound fraction is released in order to maintain equilibrium, maintaining a constant therapeutic dose for longer periods of time.

Concomitant drug administration may influence the lipoprotein-drug equilibrium,

with one drug displacing another from their lipoprotein carriers.

Increased unbound fractions of a drug may result in increased observed therapeutic and side-effects

with a direct effect on patient outcome.

Also consider -

Drugs that can affect lipoprotein levels such as Fibrates (e.g. Fenofibrate and Bezafibrate) and Isotretinoin.