Lipids

Organic substances that are insoluble in water but

soluble in organic solvents

Composed of Carbon, Hydrogen and Oxygen with

no definite ratio

Number of Oxygen atoms is very much less

compared to hydrogen atoms

Storage of energy and important component of the

cell membrane

Spingomyelin

Only phospholipid membrane

not derive from glycerol but
amino alcohol sphingosine

Niemann-Pick disease:
accumulation of spingomyelin in
the liver and spleen

Cephalin

DONT FORGET

Building blocks are fatty acids and glycerol

Transported in the blood by four major plasma

lipoprotein classes and several quantitatively
minor lipoproteins

Presence of LIPID-BOUND phosphate the only

unique feature common to all phospholipids

Mature Lung Function correlates strongly with

L/S ratio > 2

Method for L/S ratio: TLC followed by

densitometric quantitation

Main Lipids
(human plasma)

Phospholipids

Cholesterol

Unsaturated steroid alcohol

Triglycerides

Amphipathic

Fatty acids

Synthesize in the liver

Fat soluble vitamins (ADEK)

Found on the surface of lipid layers

Almost exclusively synthesize by animals; not

catabolized by most cells; does not serve as a
source of fuel

Transport and excretion is promoted by

ESTROGEN

Important constituent in the assembly of cell

membrane and bile acids

Precursor of 5 major classes of steroids:

Phospholipids

Conjugated

Most abundant lipid from phosphatidic acid

Originates in the liver

They are AMPHIPATHIC

Hydrophilic (water loving)

Hydrophobic (water fearing)

Saturated fatty acid content is reported to be an

independent risk factor for atherosclerosis

CHOLESTEROL

Progestins, glucocorticoids,
mineralocoticoids, androgens, estrogens

Forms:

Contains 2 fatty acid

Cholesterol Ester = 70%

Alter the surface tension (surfactant)

Free Cholesterol = 30%

Spingomyelin: reference material during

3rd trimester of pregnancy

Important substrates for lipoprotein metabolizing

enzyme
Forms:

Lecithin/Phosphatidyl choline

Cholesterol Ester

Present in plasma and serum

Bound to fatty acid

Neutral lipid, not charge, not found in the

surface of lipid layer, located in the center
of lipid drops

Undergoes esterification by LCAT

Excess is re-esterified by ACAT

LCAT (Lecithin-Cholesterol Acyl Transferase)

Catalyze the esterification of cholesterol

by promoting the transfer of fatty acids
from lecithin to cholesterol which results
in the formation of lysolecithin and
cholesterol ester

Synthesize in the liver and activated by

ApoA-1

ACAT (Acyl:Cholesterol Acyl Transferase)

Free Cholesterol

Present in plasma, serum, RBC

Produced via lysosomal hydrolysis and

becomes available for membrane,
hormone and bile acid synthesis

TRIGLYCERIDE

Triacylglycerol or Neutral Fat

Very hydrophobic and water insoluble

Main storage lipid in man

Allows the body to compactly store fatty acids

Breakdown of TAG by lipoprotein lipase

(LPL),epinephrine, cortisol fatty acids are
released converted into energy

Fasting requirement: 12-14 hours

FATTY ACIDS

Mostly found as constituents of phospholipids and

TAG

Mainly derived from hydrolysis of TAG in adipose

tissues

LCAT

Hydrolyzes TAG and phospholipids from

HDL, Hydrolyzes lipids on VLDL and
IDL

Catalyze esterification of cholesterol from

HDL; enables HDL to accumulate
cholesterol as cholesterol ester

Endothelial Lipase

Hydrolyzes phospholipids and TAG in

HDL

LIPOPROTEIN

Main purpose is to transport TAG and cholesterol

to sites of energy storage and utilization

TAG and Cholesterol travel in plasma not as free

floating molecules, but as part of water-soluble
complexes called LIPOPROTEIN

LIPOPROTEIN METABOLISM
Major function

Transport of triglycerides and cholesterol from

sites of exogenous origin (intestine) and
endogenous origin (liver) to sites of energy storage
and utilization

Apolipoprotein

Specific proteins that comprise the protein portion

of a lipoprotein

They interact with specific cell-surface receptors

and direct the lipids to the correct target organs
and tissues

Contain a structural motif called AMPHIPATIC

HELIX - ability of protein to bind to lipids

Lipoproteins are differentiated based on:

Particle size (expressed in Amstrong)

Small amount is present in plasma (free

unesterified form)

Chemical composition (expressed in percentage by

weight)

Most bound to albumin

Physicochemical and flotation characteristics

Very important source of energy

Electrophoretic mobility

LIPOLYTIC ENZYMES

LPL

Hydrolyzes TAG in lipoproteins, &

release of FA and glycerol

Hepatic Lipase

Four Major
Lipoprotein Classes:

Chylomicrons

Largest but the least dense lipoproteins

Density: < 0.95 kg/L

Produced by intestine

PRODUCTION: INTESTINES

Transports exogenous/dietary TAG

Major composition: 90% TAG (non-fasting plasma),

1-2% protein

CHEMICAL COMPOSITION : TAG and

Transports exogenousTAG

VLDL

Very low-density lipoproteins (VLDL)

TURBID

Secreted by the liver

PRODUCTION: LIVER

Density: 0.95-1.006 kg/L

Transports endogenous TAG

CHEMICAL COMPOSITION : TAG and

Transports endogenous TAG

Major composition: 65% TAG (fasting plasma), 16%

Chol, 6-10% protein

LDL

No Change in Appearance

Low-density lipoproteins (LDL)

Bad Cholesterol

Synthesize by the liver

PRODUCTION: LIVER

Density: 1.019-1.063

produced through the metabolism of VLDL in

circulation

CHEMICAL COMPOSITION:
Cholesterol Transports cholesterol to
tissue

constitutes about 50% of the total lipoprotein mass in

human plasma

HDL

Good Cholesterol

Transports cholesterol to the peripheral tissues

PRODUCTION: LIVER, INTESTINES

Primary target of cholesterol lowering therapy

Better marker for CHD risk

Chemical composition : Protein and

Transports cholesterol away from tissue

Important in assessing patient with or without CHD

Major composition: 50% chol, 18-20% protein

Minor lipoproteins

Intermediate-density lipoprotein or IDL

Product of VLDL catabolism

Migrates pre-beta or beta region

Lipoprotein (a) or Lp(a)

Sinking pre-beta Lipoprotein

Variable migration:n pre-beta, sometimes between

LDL and albumin

Increased level may indicate premature CHD and

stroke

Independent risk factor for atherosclerosis

Density: 1.045 1.080 kg/L

High-density lipoproteins (HDL)

Smallest but the most dense lipoprotein

Density: 1.063 1.21 kg/L

Produced by the liver and intestine

Transports excess cholesterol from the tissues and

returns to the liver

HDL2 transport effectively the lipids and is more

cardioprotective

Major composition: 30% phospholipids, 20% chol,

45-50% protein

LIPOPROTEIONS

ABNORMAL LIPOPROTEINS

Chylomicrons:

LpX

MILKY

Floating Creamy Layer

Abnormal lipoprotein found in patients with obstructive

biliary disease and LCT deficiency

Specific and sensitive indicator or cholestasis

apoB-48

Composed of 90% phospholipids, unesterified cholesterol and

very little esterified cholesterol
Remaining 10% is composed of apoC and some albumin
BETA VLDL

Floating beta lipoprotein

Abnormal lipoprotein accumulates in people with

type III hyperproteinemia or
dysbetalipoproteinemia

Richer in cholesterol than VLDL

Appears to result from the faulty catabolism of

VLDL

Found in the VLDL density range but migrates

with or near LDL

ApoC

Major constituent of VLDL and minor constituent

of HDL and LDL

Different groups:

ApoC-I

ApoC-II

APOLIPOPROTEIN

Activator of the enzyme

lipoprotein lipase (LPL)

Result to reduced clearance of

triglyceride-rich lipoproteins

ApoC-III

ApoE

ApoA

Major protein components of HDL

Major component:

ApoA-I

constitutes 75% of apoA in HDL

Synthesize in the liver and

intestine

Arginine-rich lipoprotein found in VLDL, IDL,

remnant lipoproteins, chylomicrons and HDL

Minor apolipoprotein

ApoD

ApoA-IV

Activator of enzyme
Lecithin:Cholesterol
Acyltransferase (LCAT)
esterifies cholesterol in plasma

Constitute 20% of apoA in HDL

Density >1.21 fraction of plasma in HDL

and also in very small amount as a
constituent of chylomicrons

Cherubs Everywhere in
Heavens Above

ApoB

Chylomicrons = All

While

HDL = ApoA

Lucifer Below

LDL = ApoB

Major protein constituent of LDL

Constitute 40% of CHON moiety of VLDL and

Chylomicrons

for he is

Several forms:

Very Bad

Minor component that makes up around

5% of HDL proteins

ApoA-II

Synthesized by the intestine and

it is found in chylomicrons

VLDL = ApoB

apoB-100

Most common form

Synthesized by the liver and

found in endogenous origin in
VLDL and LDL

Electrophoresis
Pattern: HDL, VLDL, LDL, Chylomicrons
Supporting Medium: agarose-gel

 Lipid-staining dyes: Oil Red O, Fat Red 7B, Sudan

Black B
Calculations

Autosomal recessive caused by defective

apoB synthesis

VLDL,LDL & chylomicrons = absent in the

plasma

Cholesterol and TAG = low

LDL = Total Cholesterol HDL VLDL

Friedwald Formula:

VLDL = TAG/2.175 (mmol/L)

VLDL = TAG/5 (mg/dL)

Disorders
Fredrickson Classification

TYPE 1: Hyperchylomicronemia

apoB deficiency resulting from point

mutation in apo-B

LDL and Tchol = low

VLDL and TAG = low or normal

Niemann-Pick disease (Lipid Storage Disease)

Inherited disorder of lipid metabolism

TYPE 2

Accumulation of spingomyelin in the bone

marrow, spleen, lymph nodes

Type 2A: Familial

Hypercholesterolemia

Type 2B: Mixed Defect

(Familial Combined Hyperlipidemia)

TYPE 3: Familial Dysbetalipoproteinemia

TYPE 4: Familial Hypertriglycedemia

TYPE 5

Familial Hypercholesterolemia
(Type 2a)

Autosomal dominant caused by defective or

deficient LDL receptors

Tangier's Disease

Rare autosomal recessive

Complete absence of HDL due to mutation

in ABCA1 gene on chromosome 9

Results to build up of cholesterol in the cell

Increase HDL catabolism

Yellow or orange discoloration of tonsils

and pharynx

LPL deficiency

Rare autosomal recessive

Increased Tchol and LDL

Inability to clear chylomicron particles

Familial Dysbetalipoproteinemia (Type 3)

Deficiency of ApoC-II

Accumulation of plasma VLDL rich in

cholesterol and chylomicrons remnants

VLDL fraction migrates abnormally in the

beta region (B-VLDL) creating broad
Beta band (pre B) electrophoretic pattern

Equal elevation of cholesterol and TAG and

presence of B-VLDL

(Familial LPL deficiency)

Hypobetalipoproteinemia

Pathognomonic Feature: a broad abnormal

band between VLDL and LDL (B-VLDL)

Abetalipoproteinemia (Bassen-Kornzweig
Syndrome)

LCAT deficiency

Due to mutation in LCAT gene

Fish-eye disease: milder form of LCAT

deficiency

Tay-Sachs Disease

An inherited neurodegenerative disorder of

lipid metabolism

Deficiency in enzyme hexosminidase A

Results to accumulation of spingolipids in

the brain

Chylomicron Retention Disease (Anderson's

Disease)

Only ApoB-48 is affected

Characterized by hypocholesterolemia,
chronic diarrhea, deficiency of fat soluble
vitamins