Lipids Spingomyelin

Organic substances that are insoluble in water but Only phospholipid membrane
soluble in organic solvents not derive from glycerol but
amino alcohol sphingosine
Composed of Carbon, Hydrogen and Oxygen with
no definite ratio Niemann-Pick disease:
accumulation of spingomyelin in
Number of Oxygen atoms is very much less the liver and spleen
compared to hydrogen atoms
Cephalin
Storage of energy and important component of the
cell membrane 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

Main Lipids Method for L/S ratio: TLC followed by

(human plasma) densitometric quantitation

Phospholipids CHOLESTEROL

Cholesterol Unsaturated steroid alcohol

Triglycerides Amphipathic

Fatty acids Synthesize in the liver

Fat soluble vitamins (ADEK) Found on the surface of lipid layers

Phospholipids Almost exclusively synthesize by animals; not

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

Most abundant lipid from phosphatidic acid Transport and excretion is promoted by
ESTROGEN
Originates in the liver
Important constituent in the assembly of cell
They are AMPHIPATHIC membrane and bile acids
Hydrophilic (water loving) Precursor of 5 major classes of steroids:

Hydrophobic (water fearing) Progestins, glucocorticoids,

mineralocoticoids, androgens, estrogens
Saturated fatty acid content is reported to be an
independent risk factor for atherosclerosis Forms:

Contains 2 fatty acid Cholesterol Ester = 70%

Alter the surface tension (surfactant) Free Cholesterol = 30%

Spingomyelin: reference material during Cholesterol Ester

3rd trimester of pregnancy
Present in plasma and serum
Important substrates for lipoprotein metabolizing
enzyme Bound to fatty acid

Forms: Neutral lipid, not charge, not found in the

surface of lipid layer, located in the center
Lecithin/Phosphatidyl choline 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
Small amount is present in plasma (free
unesterified form)
Most bound to albumin
Very important source of energy
LIPOLYTIC ENZYMES
LPL
Hydrolyzes TAG in lipoproteins, &
release of FA and glycerol
Hepatic Lipase
Hydrolyzes TAG and phospholipids from
HDL, Hydrolyzes lipids on VLDL and
IDL
LCAT
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)
Chemical composition (expressed in percentage by
weight)
Physicochemical and flotation characteristics
Electrophoretic mobility
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 CHEMICAL COMPOSITION : TAG and

Transports exogenousTAG
Major composition: 90% TAG (non-fasting plasma),
1-2% protein VLDL

Very low-density lipoproteins (VLDL) TURBID

Secreted by the liver PRODUCTION: LIVER

Density: 0.95-1.006 kg/L CHEMICAL COMPOSITION : TAG and

Transports endogenous TAG
Transports endogenous TAG
LDL
Major composition: 65% TAG (fasting plasma), 16%
Chol, 6-10% protein No Change in Appearance

Low-density lipoproteins (LDL) Bad Cholesterol

Synthesize by the liver PRODUCTION: LIVER

Density: 1.019-1.063 CHEMICAL COMPOSITION:

Cholesterol Transports cholesterol to
produced through the metabolism of VLDL in tissue
circulation
HDL
constitutes about 50% of the total lipoprotein mass in
human plasma Good Cholesterol

Transports cholesterol to the peripheral tissues PRODUCTION: LIVER, INTESTINES

Primary target of cholesterol lowering therapy Chemical composition : Protein and

Transports cholesterol away from tissue
Better marker for CHD risk
Minor lipoproteins
Important in assessing patient with or without CHD
Intermediate-density lipoprotein or IDL
Major composition: 50% chol, 18-20% protein
Product of VLDL catabolism
High-density lipoproteins (HDL)
Migrates pre-beta or beta region
Smallest but the most dense lipoprotein
Lipoprotein (a) or Lp(a)
Density: 1.063 1.21 kg/L
Sinking pre-beta Lipoprotein
Produced by the liver and intestine
Variable migration:n pre-beta, sometimes between
Transports excess cholesterol from the tissues and LDL and albumin
returns to the liver
Increased level may indicate premature CHD and
HDL2 transport effectively the lipids and is more stroke
cardioprotective
Independent risk factor for atherosclerosis
Major composition: 30% phospholipids, 20% chol,
45-50% protein Density: 1.045 1.080 kg/L

LIPOPROTEIONS ABNORMAL LIPOPROTEINS

Chylomicrons: LpX

MILKY Abnormal lipoprotein found in patients with obstructive

biliary disease and LCT deficiency
Floating Creamy Layer
Specific and sensitive indicator or cholestasis apoB-48

Composed of 90% phospholipids, unesterified cholesterol and Synthesized by the intestine and
very little esterified cholesterol it is found in chylomicrons
Remaining 10% is composed of apoC and some albumin ApoC
BETA VLDL Major constituent of VLDL and minor constituent
of HDL and LDL
Floating beta lipoprotein
Different groups:
Abnormal lipoprotein accumulates in people with
type III hyperproteinemia or ApoC-I
dysbetalipoproteinemia
ApoC-II
Richer in cholesterol than VLDL
Activator of the enzyme
Appears to result from the faulty catabolism of lipoprotein lipase (LPL)
VLDL
Result to reduced clearance of
Found in the VLDL density range but migrates triglyceride-rich lipoproteins
with or near LDL
ApoC-III
APOLIPOPROTEIN
ApoE
ApoA
Arginine-rich lipoprotein found in VLDL, IDL,
Major protein components of HDL remnant lipoproteins, chylomicrons and HDL
Major component: Minor apolipoprotein
ApoA-I ApoD
constitutes 75% of apoA in HDL Minor component that makes up around
5% of HDL proteins
Synthesize in the liver and
intestine ApoA-IV
Activator of enzyme Density >1.21 fraction of plasma in HDL
Lecithin:Cholesterol and also in very small amount as a
Acyltransferase (LCAT) constituent of chylomicrons
esterifies cholesterol in plasma

ApoA-II
Cherubs Everywhere in
Constitute 20% of apoA in HDL Chylomicrons = All
Heavens Above
ApoB
While HDL = ApoA
Major protein constituent of LDL
Lucifer Below LDL = ApoB
Constitute 40% of CHON moiety of VLDL and
Chylomicrons for he is
VLDL = ApoB
Several forms: Very Bad

apoB-100

Most common form Electrophoresis

Pattern: HDL, VLDL, LDL, Chylomicrons

Synthesized by the liver and
found in endogenous origin in Supporting Medium: agarose-gel
VLDL and LDL
 Lipid-staining dyes: Oil Red O, Fat Red 7B, Sudan
Black B
Calculations
LDL = Total Cholesterol HDL VLDL
Friedwald Formula:
VLDL = TAG/2.175 (mmol/L)
VLDL = TAG/5 (mg/dL)
Disorders
Fredrickson Classification
TYPE 1: Hyperchylomicronemia
(Familial LPL deficiency)
TYPE 2
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
Increased Tchol and LDL
Familial Dysbetalipoproteinemia (Type 3)
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
Pathognomonic Feature: a broad abnormal
band between VLDL and LDL (B-VLDL)
Abetalipoproteinemia (Bassen-Kornzweig
Syndrome)
Autosomal recessive caused by defective
apoB synthesis
VLDL,LDL & chylomicrons = absent in the
plasma
Cholesterol and TAG = low
Hypobetalipoproteinemia
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
Accumulation of spingomyelin in the bone
marrow, spleen, lymph nodes
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
Inability to clear chylomicron particles
Deficiency of ApoC-II
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 Characterized by hypocholesterolemia,
Disease) chronic diarrhea, deficiency of fat soluble
vitamins
Only ApoB-48 is affected