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LIPIDS & LIPOPROTEINS

They are commonly referred to as fats, composed mostly of carbon-hydrogen bonds.


They are primary sources of fuel; they provide stability to cell membrane and allow for transmembrane
transport.
They are insoluble in blood, but soluble in organic solvents (acetone and alcohol)
They require special transport mechanisms (lipoproteins) for circulation in the blood.
Major lipids: phospholipids, cholesterol, Triglycerides, Fatty acid, Fat soluble vitamins (ADEK)

Phospholipids (conjugated lipids)

Most abundant lipids derived from phosphatidic acid.


It originates in the liver and intestine.
Formed by conjugation of two fatty acids and a phosphorylated glycerol.
They are amphipathic, which means they contain polar hydrophilic (water-loving) head groups and non polar
hydrophobic (water-fearing) fatty acid side chains.
It is similar in structure to triglycerides, except that they contain two fatty acids.
They alter fluid surface tension (surfactant) spingomyelin serves as a reference material during 3rd trimester of
pregnancy because its concentration is constant as oppose to lecithin.
It participates in cellular metabolism and blood coagulation.
Quantitative analysis is rare in laboratory medicine it provides little added information in cases of
dysbetalipoproteinemia.
Phospholipids can be measured in disorders characterized by altered phospholipids compositio9n and
lipoprotein distribution.
Reference value: 150-380 mg/dL

Forms of phospholipids:

1. Lecithin/Phosphatidyl choline - 70%

2. Spingomyelin - 20%

3. Cephalin - 10%

The lipids concentration in amniotic fluid reflects the lipids present in intrapulmonary secretion.
Mature lung function correlates strongly with L/S 2.
The status of fetal lung maturation is estimated from the evaluation of pulmonary surfactant in amniotic fluid
the lecithin/sphingomyelin ratio (L/S) and phosphatidyl glycerol (PG) by chromatography or the microviscosity
by fluorescence polarization.
TLC followed by densitometric quantitation is the method for L/S ratio.
Microviscosity of amniotic fluid can be measured by fluorescence polarization.
Spyngomyelin
- Is the only phospholipid in membranes that is not derived from glycerol but from amino alcohol called
sphingosine.
- Essential component of cell membranes (RBC and nerve sheath)
- It accumulates in the liver and spleen of patients suffering from Niemann-Pick disease (lipid storage disorder).
Cholesterol/ 3-hydroxy-5,6-cholestene
Is an unsaturated steroid alcohol containing four rings, and it has a single C-H side chain tail similar to
fatty acids.
Is amphiphatic = A-ring is the hydrophilic Part of cholesterol.
It is found on the surface of lipid layers; synthesized in the liver.
It is almost exclusively synthesized by animals; not catabolised by most cells does not serve as a source
of fuel.
Its transport and excretion is promoted by estrogen.
Important constituent in the assembly of cell membranes and bile acids.
It should be measure in all adults 20 years of age and older atleast once every 5 years (healthy
individuals).
Precursor of five major classes of steroids: progestins, glucorticoids, mineral ocorticoids, androgens and
estrogens.
Reference values: <200 mg/dL = desirable
200-239 mg/dL = borderline hi9gh
240 mg/dL = high cholesterol
Diagnostic significance:
It evaluates the risk for atherosclerosis, myocardial and coronary arterial occlusions.
It is also used as thyroid, liver and renal functions test; and for DM studies.
It is also used to monitor effectiveness of lifestyle changes and stress management.

Forms of Cholesterol:

1. Cholesterol Ester (CE) 70%


Present in plasma and serum
It is the cholesterol bound to fatty acids (hydrophobic form)
It undergoes esterification by LCAT.

Lecithin-Cholesterol Acyl Transferase (LCAT)

Normally present in human plasma, it catalyzes 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.
It is synthesized in the liver.
Apo A-1 is the activator of LCAT
2. Free Cholesterol (FC) - 30%
Present in plasma, serum and RBC
It is a polar nonesterified form of alcohol.

Methodologies:

Either plasma or serum can be used for measurements.


2 weeks prior to testing, the person should be in its usual diet.
Total cholesterol (TC) concentration is measured rather than its forms.
Cholesterol may be assayed from nonfasting blood samples fasting has little effect on TC.
Cholesterol increase with age; woman have lower values than men except after the age of 50
increases at a rate of 2 mg/dL/year between 50 and 60 years old.
I. Chemical Methods

The presence of double bonds and hydroxyl group in the sterols structure makes it possible for cholesterol to
carry out a colorimetric assay.

Principle: Dehydration and oxidation of cholesterol to form a colored compound.

1. Liebermann Burchardt Reaction

End Product = Cholestadienyl Monosulfonic Acid (green end color)

2. Salkowski Reaction

End Product = Cholestadienyl disulfonic Acid (red end color)

Precautions:

1. Avoid hemolyzed blood falsely increases cholesterol levels.

2. Avoid icteric specimens 5-6mg% increase in choke/mg bilirubin above normal.

3. Avoid water contamination.

4. Precise and accurate timing for color development must be observed.

Color Developer Mixture (Liebermann Burchadt Reagent)

a. Glacial acetic acid


b. Acetic anhydride
c. Concentrated H2SO4

General methods:

1. One-Step Method = Colorimetry (pearson, Stern, and Mac Gavack)

2. Two-Step Method = C + extraction (Bloors)

3. Three-Step Method = C + E + Saponification (Abell-Kendal)

4. Four-Step Method = C + E + S + Precipitation (Schoenheimer Sperry, Parekh and Jung)

II. Enzymatic Methods

Cholesterol esterase

Cholesterol ester + H2O Cholesterol + fatty acids

Cholesterol oxidase

Cholesterol + O2 Cholest-4-en-3-one + H2O2


peroxidase

H2O2 + phenol + 4-aminoantipyrine Quinoneimine dye

CDC reference method (Abell, Levy, and Brodie Method)

Uses hexane extraction after hydrolysis with alcoholic KOH followed by frication with Liebermann-Burchardt
color reagent.

Increased Cholesterol: decreased Cholesterol

1. Hyperlipoproteinemia types II, III, V 1. Severe hepatocellular disease

2. Biliary cirrhosis 2. Malnutrition

3. Nephrotic syndrome 3. Severe burns

4. Poorly controlled diabetes mellitus 4. Hyperthyroidism

5. Alcoholism 5. Malabsorption Syndrome

6. Primary hypothyroidism

Triglyceride/Triacylglecyrol (Neutral fat)

It contains 3 molecules of fatty acids and one molecule of glycerol by ester bonds.
Do not contain charged or hydrophilic groups very hydrophobic and water insoluble.
Main storage lipid in man (adipose tissue) constitutes 95% of stored fat and the predominant form of glyceryl
ester found in plasma.
Allows the body to compactly store long carbon chains (fatty acids) for energy that can be used during fasting
states between meals.
When tryiglyceride (TAG) are metabolized, their fatty acids are released to the cells and converted into energy
provides excellent insulation.
The breakdown of TAG are facilitated by lipoprotein lipase (LPL), epinephrine and cortisol.
An average person ingests, absorbs, resynthesizes, and transports about 60g-130g of fat daily in the body,
mostly in the form of triglycerides.
People with low caloric intake have relatively low triglycerides levels.
Fasting Requirement: 12-14 hours
Reference values: 10-190mg/dL
<150mg/dL - normal
150-199mg/dL - borderline high
200-499mg/dL - high TAG
>500 - very high TAG (acute and recurrent pancreatitis)
Diagnostic significance:
It evaluates suspected Atherosclerosis and measures the bodys ability to metabolize fat.

Methodologies:

Prior to venipuncture, ideally patients should undergo fasting for 12 hours.


Either plasma or serum can be used for measurements.
Postural changes decrease TAG levels by almost 50% (upright to supine position)
Like TC, it increases at a rate of 2 mg/dL/year between 50 And 60 years old.
Fasting TAG 200mg/dL are at risk for coronary artery disease because of atherogenic VLDL remnants.
If lipemic serum will be frozen at -20C for assay at a later date, the specimen should be warmed thoroughly to
37C and mixed before the test.

I. Chemical Methods

1. Colorimetric Method (Van Handel & Zilversmith)

Alcoholic KOH
Triglycerides Glycerol + fatty acids (FA)

Glycerol Oxidized by periodic acid (+) Blue color compound

2. Fluorometric Method (Hanthzsch Condensation)

alc. KOH
Triglycerides
Glycerol + FA

Glycerol Oxidized by periodic acid HCHO

HCHO + Diacetyl Acetone + NH3 Diacetyl lutidine compound

II. Enzymatic Method

Glycerol Kinase Method

Lipase
(A) Triglycerides Glycerol + FA

Glycerol kinase
Glycerol + ATP Glycerol PO4 + ADP

Private Kinase
ADP + Phosphoenol Pyruvate ATP + Pyruvate

LDH
Pyruvate + NADH Lactate + NAD

Lipase
(B) Triglycerides Glycerol + FA

Glycerol Kinase
Glycerol + ATP Glycerol PO4 + ADP
Glycerol-PO4 + dehydrogense
Glycerol PO4 + NAD Dihydroxyacetone PO4 + NADH

Diaphorase
NADH + tetrazolium dye Formasan + NAD

CDC reference method (Modified Van Handel Zilversmith)

Involves alkaline hydrolysis, solvent extraction with chloroform and the extract is treated with silicic acid, and a
color reaction with chromotropic acid, giving rise to a pink end color.

Increased TAG: Decreased TAG:

1. Hyperlipoproteinemia types I, IIb, III, IV, V 1. Malabsorption syndrome

2. Alcoholism 2. Hyperthyroidism

3. Nephrotic syndrome 3. Malnutrition

4. Hypothyroidism 4. Brain infarction

5. Pancreatitis

Fatty acids

Are linear chains of carbon hydrogen bonds that terminate with a carboxyl group.
As to length, they can be classified as short chain (4-6 carbon atoms), medium chain (8-12 carbon atoms) or long
chains (>12 carbon atoms)
As to the number of C=C bonds, they can be saturated (without double bonds) or unsaturated (with double
bonds) fatty acids.
It is mostly found as constituents of phospholipids or triglycerides.
Mainly derived from hydrolysis of triglycerides in adipose tissues.
They are very important sources of energy.
They provide the substance for conversion to glucose (gluconeogenesis).
Only small amount is present in plasma (free unsterified form), most is found to albumin.
The polyunsaturated and cis-monosaturated fatty acids are not associated with elevated serum LDL cholesterol.
Examples: palmitic acid, stearic acid, oleic acid, linoleic acid and arachidonic acid.
Reference values: 9-15 mg/dL

Lipid and lipoprotein metabolism

Lipids in the circulation are organized into large lipoprotein particles with apolipoproteins characteristics of
different classes. These apolipoproteins aid in the solubilization of the lipids and also in their transfer from the
gastrointestinal tract to the liver, which contains specific receptors for apolipoproteins.
The dietary or exogenous pathway of lipid transport involves absorption of triglycerides (TAG) and cholesterol
(Ch) through the intestine, with formation and release of chylomicrons(CM) into the Lymph and into the blood
by way of the thoracic duct.
The CM release TAG to adipose tissue as they circulate. The lipoprotein lipase (LPL) liberates fatty acids (FA)
from TAG, thereby reducing the size of CM to become remnants which are in turn taken up by the liver. The free
FA liberated from TAG is taken up by muscle and adipose tissue.
In the endogenous pathway, production of TAG from FA by the liver take place, with synthesis of VLDL particles
containing apo B100 and E. These VLDL particles are then converted by lipoprotein lipase (LPL) to IDL that can
either be removed by the liver through ApoE or be converted to LDL. The Ch-rich LDL particles can be taken up
by the liver or into other tissues for steroid synthesis or part of cell membranes.
The HDL particles mobilize Ch from tissues and reintroduce it for continued metabolism or excretion. LCAT
catalyzes for esterification of Ch in HDL3, converting HDL3 to HDL2. This fraction of Ch can be transferred to VLDL
to participate in the metabolism of membrane and steroid synthesis, or be taken up by the liver and then
excreted into bile.
The above-mentioned process for lipid transport and clearance depend on apolipoprotein concentrations and
on the amount of lipid in diet.

Enzymes that participate in lipoprotein metabolism (lipolytic enzymes)

1. Lipoprotein Lipase (LPL) hydrolyzes TAG in lipoproteins, and released of fatty acid and glycerol.

2. Hepatic lipase hydrolyzes TAG and phospholipids from HDL; hydrolyzes lipids on VLDL and IDL.

3. Lecithin Cholesterol Acyl Transferase (LCAT) - catalyzes the esterification of cholesterol from HDL; enables HDL to
accumulate cholesterol as cholesterol ester.

4. Endothelial Lipase hydrolyzes phospholipids and TAG in HDL.

LIPOPROTEINS

Large macromolecular complexes of lipids with specialized proteins known as apolipoproteins.


Its main purpose is to transport TAG and cholesterol to sites of energy storage and utilization.

Apolipoprotein

Helps to keep the lipids solution during circulation through the blood stream.
They interact with specific cell surface receptors and direct the lipids to the correct target organs and tissues in
the body present on the surface of lipoprotein particles.
Maintains the structural integrity of the lipoprotein (LPP) complex.
They contain a structural motif called an amphipatic helix ability of proteins to bind to lipids.

Major lipoproteins

1. Chylomicrons (CM)

The largest and the least dense of the lipoproteins particles.


Density: <0.95 kg/L
Produced by the intestine; completely cleared within 6-9 hours post prandial.
Transport exogenous/dietary TAG to liver, muscles and fat depot.
Major composition: 90% TAG (non-fasting plasma) + 1-2% protein.
Apolipoproteins: Apo B-48 and Apo C, Apo E

2. Very Low Density Lipoprotein/Pre-Beta Lipoprotein (VLDL)

It is secreted by the liver.


Density: 0.95 1.006 kg/L
Transports endogenous TAG from the liver to muscle, fat depots and peripheral tissues.
Prolonged consumption of high fat diet leads to elevated TAG in the VLDL particles.
Major composition: 65% TAG (fasting plasma); 16% CE + 6-10% protein
Apolipoproteins: Apo B-100, Apo C and Apo E

3. High Density Lipoprotein/Alpha lipoprotein (HDL)

The smallest lipoproteins but most dense (15-12nm)


Density: 1.063-1.21 kg/L
Produced by the liver and intestine (nascent disked-shaped particles)
Transports excess cholesterol from the tissues and return it to the liver (reverse cholesterol transport)
HDL2 transports effectively the lipids to the liver and more cardio protective.
CDC reference methods: ultracentrifugation, precipitation, with heparin-MnCl2 and Abell-Kendal Assay (3 step
method)
Major composition: 30% phospholipid; 20% CE + 45-50% protein
Apolipoproteins: Apo A-I, Apo A-II, Apo C
Reference values: <40mg/dL low (cut off level)
60mg/dL high
4. Low Density Lipoprotein/Beta lipoprotein (LDL)
Synthesized by the liver.
Density: 1.019-1.063 kg/L
The major end product resulting from the catabolism of VLDL.
Transports cholesterol to the peripheral tissues.
It constitutes about 50% of the total LPP in plasma.
The most cholesterol rich of the lipoproteins and most atherogenic.
Primary target of cholesterol lowering therapy; better marker for CHD risk.
Important in assessing patients with or without coronary heart disease (CHD)
Major composition: 50% CE + 18% protein and phospholipid
Apolipoproteins: Apo B-100 and Apo E
Research method: beta quantification method.
Reference Values: <100 mg/dl = optimal
100-129 mg/dL = near/above optimal
130-159 mg/dL = borderline
160-189 mg/dL = high
190 mg/dL = vey high

CHEMICAL COMPOSITION OF LIPOPROTEINS


Cholesterol
TAG Phospholipid Protein
Ester (CE)
Chylomicrons 80-95% 2-4% 3-6% 1-2%
VLDL 45-65% 16-22% 15-20% 6-10%
LDL 4-8% 45-50% 18-24% 18-22%
HDL 2-7% 15-20% 26-32% 45-55%

Minor and Abnormal Lipoproteins:


1. Intermediate density lipoprotein (IDL)
Product of VLDL catabolism
It is converted to LDL subclass of LDL
It migrates either in the pre or region (electrophoresis)
Defective clearance of IDL in type 3 hyperlipoproteinemia is probably due to deficiency of Apo E-III
Density:1.006-1.019 kg/L = causing it to float on the 1.063 density potassium bromide solution

2. Lipoprotein (a)/Lp (a)

Similar to LDL (density and composition) LDL like particles (LDL variant) that have molecule of Apo (a) linked to
Apo B-100 by a disulfide bond.
Variable migration = pre , or sometimes between LDL and albumin.
It is known as sinking pre lipoprotein due to electrophoretic mobility same as VLDL but density like LDL.
It is isolated in the LDL-HDL density range by ultracentrifugation.
Its complex structure is also similar to plasminogen.
Increased levels may indicate premature coronary heart disease and stroke independent risk factor for
atherosclerosis.
It contains Apo B-100
Density: 1.045-1.080 kg/L

3. Lipoprotein X

It is an abnormal lipoprotein found in obstructive jaundice & LCAT deficiency.


Specific and sensitive indicator of cholestasis.
The lipid content is mostly phospholipid and free cholesterol (90%)
It contains Apo C and albumin.

4. -VLDL (floating lipoprotein)

It is known as abnormally migrating -VLDL by ultracentrifugation but migrates with LDL in the region during
electrophoresis.
Found in type 3 hyperlipoproteinemia or disbetalipoiproteinemia.
Rich in cholesterol content than VLDL due to defective catabolism of VLDL, there is failure to convert VLDL to
LDL causing IDL to also accumulate.
Density: <1.006 kg/L

Lipoprotein methodologies:

Sample collected using serum separator tubes is the preferred sample.


EDTA plasma is the choice for research studies of lipoprotein fractions.
If testing is done in nonfasting samples, only total cholesterol (TC) and HDL-C can be measured.
In the fasting state, most plasma TAG is present in VLDL: non fasting state in chylomicrons.
Lipemic samples occur in non fasting blood, in patients with hyperlipidemia or receiving total parenteral
nutrition (TPN) therapy.
Lipemic samples may be pretreated by ultracentrifugation or enzymatic cleavage to remove lipids because it can
interfere with spectrophotometric, turbidimetric and immunoassays.
Lipoproteins are separated based on electrophoresis and density (ultracentrifugation)
TC HDL C = non HDL-C

1. Ultracentrifugation (density gradient)

Reference method for quantitation of lipoproteins.


Is based on the protein and triglyceride contents of lipoproteins ultracentrifugation of plasma for 24 hours.
It is expressed in svedverg (s) units.
Reagent: potassium bromide solution with 1.063 density.

2. Electrophoresis

HDL,VLDL, LDL, chylomicrons (electrophoretic pattern)


VLDL migrates with the a-2 globulin (pre ).
Supporting medium: agarose gel sensitive: resolves lipoprotein classes.

3. Chemical precipitation

It uses polyanions (heparin and divalent cations), polyethelyne glycol.


The most consistent analytical error involved in the HDL-Chole assay is due to the presence of a small amount of
apo-B containing lipoiproteins (LPPs)
Enzymatic with coupled detergent precipitation is the most useful LPP tests.
HDL = dextran sulfate (synthetic heparin) with magnesium (precipitants)
= ultracentrifugation, heparin manganese precipitation and Abell-kendall assay (CDC reference 3-step
procedure)
LDL = beta quantification combines ultracentrifugation and chemical precipitation: EDTA plasma is the sample.

4. Chromatographic Methods

It utilizes either Gel Chromatography or affinity Chromatography

5. Inmmuno Chemical methods

It uses antibodies specific to epitopes on the apolipoproteins.

6. Immunoassay or immunonephelometry apolipoproteins assay

It is based on the measurement of turbidity created by apolipoprotein-antibody complexes.


Studies have shown that apo A-1 and apo B may be letter indicators of altherosclerotic disease than
lipoprotein assay.
Lipoprotein (a) is measured by immunoturbidimetric assay.

Formula for LDL-cholesterol (LDL-C) = Total Cholesterol HDL-VLDL

Friedewald Method (indirect method):

VLDL (mmol/L) = Plasma triglyceride


2.175

VLDL (mg/dL) = Plasma triglyceride


5.0

De Long Method (indirect method):

VLDL (mmol/L) = Plasma triglyceride


2.825

VLDL (mg/dL) = Plasma triglyceride


6.5
Significant Human Apolipoproteins

Plasma concentration
Apolipoprotein Major lipoproteins Mr * (kDa) Amino acids Chromosome (mol/L) (mg/dL)
A-I HDL 29 243-245 11 32-46 90-130
A-II HDL 17.4 154 1 18-29 30-50
A-IV 44.5 396 11
(a) Lp(a) 350-700 Variable 6
B-100 VLDL, IDL,LDL 512.7 4536 2 1.5-1.8 80-100
B-48 CM 240.8 2152 2 <0.2 <5
C-I CM,LDL 6.6 57 19 6.1-10.8 4-7
C-II CM,LDL 8.9 78 or 79 19 3.4-9.1 3-8
C-III CM 8.8 79 11 9.1-17.1 8-15
D HDL 19 169 3
E CM, LDL, IDL 34.1 299 19 0.8-1.6 3-6

Apolipoprotein Functions and significant characteristics

Apolipoprotein Main Function (if known) Comments


Distribution
A-I HDL Activates LCAT which esterifies Synthesized in liver in intestine
Cholesterol in plasma
A-II HDL May inhibit lipoprotein and hepatic lipases and
increase plasma triglyceride
A-IV HDL,CM and May be a cofactor for LCAT
free in plasma
B-100 VLDL and LDL Carboxy terminal recognition Very large protein, synthesized in liver; found in
signal targets LDL to the LDL (apo lipoproteins with lipids of endogenous origin
B,E) receptor (i.e, not chylomicrons)
B-48 CM Not recognized by LDL receptor Synthesized in intestine, encoded by same gene
and has same amino terminus as apoB-100.
Differential production of the two proteins
involves RNA editing
C-I CM and VLDL May inhibit hepatic uptake of VLDL and
cholesterol ester transfer protein
C-II CM and VLDL Activate lipoprotein lipase Deficiency causes reduced clearance of
triglyceride rich lipoproteins
C-III VLDL, HDL Appears to inhibit lipolysis of
trglyceride-rich lipoproteins; may
regulate clearance rate of
remnant particles.
C-IV CM, HDL May be involved in lipid absorption
D HDL Activates LCAT
E CM, VLDL, IDL, Recognition factor that targets E-2, E-3, and E-4 isoforms E-4 is associated with
remnants chylomicron and VLDL remnants high LDL-C, higher risk of CHD and alzheimers
And HDL to hepatic receptor: also binds to disease E-2 associated with type 3
cell surface LDL receptors hyperlipoproteinemia
H HDL, VLDL and Unknown, possibly related to Antibodies against apoH, or 2- glycoprotein-I
CM activation of LPL are a subset of antiphospholipid antibodies and
may be associated with hyperthrombosis and
stroke
Apo (a) Lp(a) Homologous to plasminogen, may be
prothrombotic. Bound to apoB-100 by disulfide
linkage.
Disorder associated with lipids and lipoprotein

1) Familial hypercholesterolemia (type 2a)


Autosomal dominant disorder caused by defective or deficient LDL receptors.
Defective LDL receptors cannot bind or clear LDL = TC and LDL-C (2-3x above normal)
(+) xanthelasma and planar (tendon) xanthomas
2) Familial Dysbetalipoproteinemia (type 3 hyperlipoptroteinemia)
It involves accumulation of plasma VLDL rich in cholesterol and chylomicron remnants.
It is also associated with the presence of apo E2/2 (rare of apo E)
It involves both the endogenous and exogenous pathway of lipoprotein metabolism.
The VLDL fraction migrates abnormally in the region (-VLDL) creating broad band ( pre )
electrophoretic pattern.
(+) xanthomas (palmar and eruptive xanthomas)
VLDL-Chole: total TAG ratio: 0.689-0.919 (RF: 0.230-0.575)
3) Abetalipoproteinemia (Basses-Kornsweig Syndrome)
Autosomal recessive disorder, defective apo B synthesis
VLDL, LDL, and chylomicrons = absent from plasma
Chole and TAG = low
Defects in absorption of lipids (fat-soluble Vitamins AEK) deficient fat soluble vitamins.
It is characterized by cerebellar ataxia, acanthocytosis, fat malabsorption.
4) Hypobetalipoproteinemia
It is due to apo B deficiency resulting from point mutation in apo B
LDL chole & total cholesterol = low levels
VLDL-chole & total TAG = low or normal levels
5) Niemann-Pick disesase (lipid storage disease)
An inherited disorder of lipid metabolism, in which there are accumulations of spingomyelin in the bone
marrow, spleen and lymph nodes.
It involves the deficiency of enzymes responsible for removing phosphorylcholine from spingomyelin.
6) Tangiers disease
A rare familial deficiency of HDL, characterized by low blood cholesterol and an abnormal orange or
yellow discoloration of the tonsils and pharynx.
HDL is abnormal and significantly reduced due to increased HDL catabolism.
7) Lipoprotein lipase (LPL) deficiency
Results to inability to clear chylomicron particles, creating the classic type 1 chylomicronemia
syndrome (TAG = 10,000 mg/dL or 113.0 mmol/L)
Patients with this condition do not delelop premature coronary disease implying that chylomicrons
themselves are not atherogenic.
It is characterized by abdominal pain and pancreatitis.
LPL is essential for hydrolysis of TAG and conversion of chylomicrons to chylomicron remnants.
Deficiency of Apo C-II also results to chylomicronemia.
8) Lecithin Cholesterol Acyl Transferase (LSAT) Deficiency
Fish-eye disease (milder form of LCAT deficiency)
Due to mutation in the LCAT gene.
HDL-cholesterol levels are typically low (<10mg/dL)
9) Tay-sachs disease
An inherited neurodegenerative disorder of lipid metabolism characterized by a deficiency of the
enzyme hexosaminidase A, which results in the accumulation of spingolipids in the brain.

FREDRICKSON CLASSIFICATION

Types TAG CHOL LDL VLDL CHYLO

1.Type I Inc Inc


Inc - incomplete
- familial LPP lipase deficiency
2.Type 2a Inc Inc
- Familial hypercholesterolemia
Type 2b mixed defect
- Familial Combined Hyperlipidemia Inc Inc Inc Inc
3. Type 3 Inc Inc Inc
- Familial Dysbetalipoproteinemia
4. Type 4 Inc Inc
- Familial hypertriglycedemia
5. Type 5 Inc Inc Inc Inc

Notes to Remember

Lipemia in plasma is cleared as it passes through various tissues by the enzyme, lipoprotein lipase (LPL) which is
present in the capillary walls of many tissues mainly adipocytes, skeletal and cardiac muscles, spleen and lungs
A block in the progression from chylomicron (CM) to chylomicron remnants resyluts in the accumulation of CM
in types 1 and 5.
A block in LDL metabolism and defective apo B protein that does not bind to LDL receptor or mutant LDL
receptor that does not recognize apo B type 2
Familial combined hyperlipidemia (type 2b) is the most common primary hyperlipidemia.
The presence of floating -VLDL in type 3 dysbetalipoproteinemia is due to failure to convert VLDL to LDL
causing IDL to accumulate.
A block in the conversion of VLDL to IDL and LDL results to elevated TAG and VLDL, but LDL is normal type 4.
The production of excesss insulin leads to hypertriglyceridemia also seen in TYPE IV
Types 1 ,4, 5 = LPL deficiency: inability to breakdown TAG
High levels of cholesterol in the HDL fraction are negatively associated with cardiovascular disease, while
elevated levels of cholesterol in the LDL fraction are positively associated with it.
High HDL-C and low LDL-C = risk factors for atherosclerotic disease.