LIPIDS & LIPOPROTEINS

CLASSIFICATION OF LIPIDS (6 GROUPS)

1. Fatty Acids
2. Acylglycerols (Triglycerides & Phospholipids)
3. Cholesterol
4. Prostaglandins
5. Sphingolipids
6. Terpens

FATTY ACIDS

Most FA can be synthesized (nonessential)

Essential FA need to be in the diet
• Linoleic and linolenic

Mainly exist as esters combined with glycerol or as free unesterfied (often bound to albumin)

Further classified by their degree of saturation

FATTY ACID CATABOLISM Occurs in

Mitochondria via β-oxidation

Acetyl-CoA is the

Major end product (to use in Krebs cycle)

Ketosis (excess Acetyl-CoA and ketones) develops as

Body tries to obtain energy from fat stores

TRIGLYCERIDES

Constitute 90 % of dietary fat intake and 95% of
fat stored in tissues

Increased levels –increased risk for arteriosclerosis Indicated in blood by “creamy”
plasma layer & at high levels impart turbidity to blood (lipemia)

PHOSPHOLIPIDS BIOLOGICAL ROLE

Essential components of cell membranes

Align themselves between water phase and lipid phase (amphipathic)

Fatty acid faces inward; glycerol /alcohol outward (towards water) in lipoprotein particle

Not normally measured for cardiac risk assessment

CHOLESTEROL

Found almost exclusively in animals

Synthesis occurs in the liver and intestines (90%) and involves Acetyl CoA

A Steroid (most abundant)

Amphipathic

CHOLESTEROL ESTERFICATION

Esterfied to a fatty acid within cells

Roughly 2/3 of circulating cholesterol is present as cholosterol-esters

CHOLESTEROL CATABOLISM

Not readily catabolized for energy

Converted in liver to bile acids

Not all cholesterol delivered to liver is converted to bile salts.......gall stones

CHOLESTEROL CATABOLISM Converted via

Specialized endocrine cells into steroid hormones

PROSTAGLANDINS

Derivatives of fatty acids

Have “hormone-like” diverse actions

Synthesized at the site of action (in almost all tissues...NOT stored)

Have short lived effects (catabolized within seconds)

TERPENES

Fat soluble vitamins

Vitamin A
Vitamin E
Vitamin K

INTESTINAL ABSORPTION OF LIPIDS

Major steps:
(1) Emulsification and micelles formation
(2) transport into cell, (active & passive)
(3) chylomicrons

Micelle and chylomicrons

Packing unit for lipids

LIPOPROTEINS

Lipids + Protein

Triglycerides and cholesterol esters in core

Free Cholesterol and phospholipids on

Surface as a single monolayer

Protein portion (apolipoproteins) located on

The surface

The more lipid

The lower the density

The more protein

The higher the density

Based on Increasing Density (ultracentrifugation):

Chylomicrons (lowest density; float)
VLDL
IDL
LDL
Lipoprotein(a)
HDL

Based on electrophoretic mobility (slow to fast):

Chylomicrons: slowest moving
Beta lipoproteins (largely LDL)
Pre-beta lipoproteins (VLDL)
Alpha lipoproteins (HDL): fastest moving

CHYLOMICRONS

Transport dietary fat from intestines to liver and then adipose/muscle cells

Extremely little protein

Not normally present in fasting specimens
(8-12 overnight fast); presence is pathologic

Triglyceride, Phospholipid, Cholesterol and Apoplipoprotein

If excess

Creamy layer in plasma upon overnight refrigeration

VLDL (PRE-BETA) LIPOPROTEINS

Made by liver

A bit more protein (8%): Apo B-100

Transport endogenous triglycerides (derived from liver) to adipose tissue/fat

If present in high concentration

Will make the serum appear “milky” after overnight refrigeration

INTERMEDIATE-DENSITY LIPOPROTEINS (IDL)

Results from loss of fatty acids from VLDL

Major lipid: cholesterol esters

Proteins similar to VLDL but greater percentage (15%)

ApoB-100

Taken up by liver

LDL LIPOPROTEINS

Transport cholesterol from the liver to peripheral cells

21% Protein

Responsible for carrying most of your plasma cholesterol

LDL receptor proteins on cell membrane vital to uptake of cholesterol

“Bad” cholesterol

Direct relationship with CVD risk

LIPOPROTEIN(A)

Measure to assess the likelihood of CVD in an individual with normal lipid values but a strong family history of cardiovascular disease

(presence=risk factor for heart disease)

HDL LIPOPROTEINS

Transport cholesterol from peripheral tissue to liver

Major lipid is phospholipid

High protein level (50%)

“Good” cholesterol

Inverse relationship with CVD

APOPROTEINS

Major protein component of lipoproteins

Perform a variety of functions:

(1) modulate activity of enzymes that act on lipoproteins
(2) maintain the structural integrity of the complex
(3) facilitate the uptake of lipoproteins by cells

Exogenous pathway

Chylomicrons transfer dietary- derived lipids to liver

Endogenous pathways

VLDL transfers hepatic-derived lipids to cells via LDL

Reverse cholesterol transport

HDL removes excess cholesterol

CARDIOVASCULAR DISEASE (CVD)

General term for all diseases of the heart and blood vessels

Atherosclerosis is the main cause of CVD

Atherosclerosis leads to

Blockage of blood supply to the heart, damage occurs --coronary artery disease (CAD)

LDL

Directly associated with CVD

HDL

Inversely associated with CVD

VLDL

Is also Directly associated with CVD

SECONDARY CAUSES OF HYPERLIPIDEMIA

Hyperlipidemia MOST frequently secondary to other disorders

Important to rule out other diseases before treating with lipid lowering drugs

LIPOPROTEIN LIPASE DEFICIENCY

Rare (one/million)autosomal recessive characterized by hyperchylomicronemia

Extremely high Triglycerides levels: 5,000-10,000 mg/dL (normal < 150 mg/dL)
very milky looking serum

FAMILIAL COMBINED HYPERLIPIDEMIA (FCHL)

Increased plasma concentration of total cholesterol and LDL (Type IIa), Triglycerides
(type IV) or all the above (type IIb).

Triglycerides usually between 200- 400mg/dL (ref. <150mg/dL) but can see much higher.

FAMILIAL HYPERTRIGLYCERIDEMIA (COMMON)

Only moderate increase in serum triglycerides

Increased VLDL

Commonly associated with low HDL

Autosomal dominant disorder with one/500 estimated frequency in general population

TYPE V HYPERLIPOPROTEINEMIA

Increase in both chylomicrons and VLDL

What would tube of serum look like?

Pancreatitis and altered glucose tolerance common too

DYSBETALIPOPROTEINEMIA

Have accumulation of chylomicrons remnants and IDL in the serum

Premature atherosclerosis possible

Extremely rare genetic disorder – have mutant form of Apo E

FAMILIAL HYPERCHOLESTEROLEMIA

Defect in the LDL receptor pathway

Increase deposition of LDL in skin, tendons and arteries

Average plasma LDL levels 2-3x normal

HYPOALPHALIPOPROTEINEMIA

ALPHA = HDL

Decreased or absent HDL

Increased risk of CVD

Tangier’s disease

Mutation in ABCA1 gene

Total absence of alpha lipoproteins

Massive cholesterol deposits in macrophages

Orange (tang) colored tonsils

Patients are susceptible to atherosclerosis

LIPID STORAGE DISEASES (LYSOSOMAL)

Lysosomes

Function like an “intracellular digestive tract”
If enzymes are absent or deficient, metabolites will
accumulate

LIPID STORAGE DISEASES (LYSOSOMAL) Disorders

Niemann Pick

Gaucher’s --Eastern European Jewish decent

Tay-Sach’s --Eastern European Jewish (Ashkenazi)