Lipids

&
lipoproteins
CC-Lecture by DIANNE JAGONIA, RMT
 LIPIDS
“FATS”
Composed mostly of C-H bonds
Insoluble in blood & water, but SOLUBLE IN
CHLOROFORM & ETHER
Provide stability to the cell membrane and allow for
membrane transport
Major lipids:
PHOSPHOLIPIDS, CHOLESTEROL, TRIGLYCERIDES, FATTY
ACIDS, FAT SOLUBLE VITAMINS (ADEK)
Linear chains of C-H bonds that 9-15mg/dL
terminate w/ a carboxyl group
Based on length:
Short-chain (4-6 C atoms)
Medium-chain (8-12 C atoms)
Long-chain (>12 C atoms)
Based on C=C bonds:
Saturated (w/o C=C)
(Cis/Trans) Mono/Poly-
Unsaturated (w/ C=C)
Only small amount is present in
plasma, mostly bound to Albumin
From hydrolysis of Triglycerides fatty acid
 phospholipids
1 glycerol + 2 esterified F.A.
(14-24 C atoms, 1 Sat. & 1
Unsat.)
“AMPHIPATHIC”
- Contain POLAR HYDROPHILIC
HEAD GROUP and
NONPOLAR HYDROPHOBIC
FATTY ACID CHAINS
From liver & intestine

150-380 mg/dL
1 glycerol + 3 F.A.
triglycerides
“TRIACYLGLYCEROL” (Neutral Reference Values
lipid)
< 150 Normal
The main storage lipid (95%) in mg/dL
man (adipose tissue)
150 – 199 Borderline
Very hydrophobic & H₂O insoluble mg/dL high
Property @ room temp:
200 – 499 High TAG
Plant sources: LIQUID (OILS) mg/dL
Animal sources: SOLID
> 500 Very high
Broken down by LPL, epinephrine mg/dL TAG
& cortisol
 Amphipathic
Unsaturated steroid alcohol
Reference Values
containing four rings (A,B,C,D)
< 200 mg/dL Desirable Synthesized in the liver
Esterified form: CHOLESTERYL
200 – 239 Borderline ESTER (very hydrophobic)
mg/dL high Uses:
Promotes fat absorption in
≥ 240 mg/dL High Chole.
the GIT
As steroid hormones
Vitamin D₃

cholesterol
LIPOPROTEINS
Large macromolecular
complexes of lipids
with specialized
proteins known as
APOLIPOPROTEINS

Chylomicrons*
VLDL*
LDL*
HDL*
chylomicrons
Contain apo B-48
Largest, yet least dense of
all
Readily float on top of
stored plasma & form a
creamy layer
Fxn: delivery of dietary
lipids to hepatic &
peripheral cells
very low density lipoprotein
Contains apo B-100, apo E,
apo Cs
Account for most of the
turbidity in fasting
hyperlipidemic plasma spx
Fxn: Carries endogenous
TAG and transfer it to the
peripheral tissues
low density lipoprotein
Contains apo B-100 Reference Values
“BAD CHOLESTEROL”
<100 mg/dL Optimal
“β-Lipoprotein”
100-129 mg/dL Near/Above
Has the tendency to Optimal
infiltrate into the 130-159 mg/dL Borderline high
extracellular space of vessel
walls, where they can be 160-189 mg/dL High
taken up by macrophages ≥190 mg/dL Very High
and turn into “FOAM CELLS”
high density lipoprotein
Contain apo A-1 & apo E
“GOOD CHOLESTEROL” Reference Values
“α-Lipoprotein”
2 forms: 40 mg/dL Cutoff level
Discoidal
Spherical (HDL₂ & HDL₃) High risk for
<35 mg/dL CHD
Fxn: Removes excess
cholesterol from peripheral
cells (Reverse Cholesterol >60 mg/dL
High HDL
Transport) (protective)
 CHARACTERISTICS OF MAJOR HUMAN
LIPOPROTEINS
Parameters Chylomicrons VLDL LDL HDL

Density (g/mL) <0.93 0.93-1.006 1.019- 1.063-

1.063 1.21
Diameter (nm) 80-1,200 30-80 18-30 5-12
Total lipid (%) 98 89-96 77 50
Total TAG (%) 84 44-60 11 3
Total Chole (%) 7 16-22 62 19

Total CHON (%) 1-2 6-10 18-22 45-55

lipoprotein (a)
LDL-like particles that have a molecule of apo (a) linked
to apo B-100 by disulfide bond
“SINKING PRE-β LIPOPROTEIN”

intermediate density lipoprotein

A VLDL remnant converted to LDL
Contains apo B-100

MINOR LIPOPROTEINS
lipoprotein X
Found in obstructive jaundice (e.g. CHOLESTASIS) & LCAT
deficiency
90% phospholipid & cholesterol
Contains Apo-C & Albumin

β - VLDL
Found in Type 3 Hyperlipoproteinemia or
dysbetalipoproteinemia
“FLOATING β LIPOPROTEIN” – same density w/ VLDL but
migrates w/LDL in β region during electrophoresis

ABNORMAL LIPOPROTEINS
lipid physiology
&
metabolism
Lipid disorders
 arteriosclerosis
Deposition of lipids in artery walls
Plaque formation
3 types:
Peripheral Vascular Dse.
Coronary Artery Dse. (Angina & MI)
Cerebrovascular Dse. (Stroke)
Treatment: Lowering of LDL (diet or
drug therapy, e.g. Statins, Ezetimibe,
Fibric acid derivatives)
 hyperlipoproteinemia
Homo/Hetero-zygous Familial Hypercholesterolemia
Due to insufficient LDL receptors
Tx. LDL Pheresis & Statin Drugs
Hypertriglyceridemia
Imbalance in the synthesis & clearance of TAG due to
deficiency in LPL and Apo C-II
Tx. Fibric acid derivatives
Familial Combined Hyperlipoproteinemia
(Dysbetalipoproteinemia)
Accumulation of cholesterol-rich VLDL and chylomicron
remnants due to defective catabolism of those particles
 lipoprotein (a) elevation
Because apo (a) has a high degree of homology with the
coagulation factor, plasminogen, it has been proposed
that it competes with plasminogen for fibrin binding
sites, thus increasing plaque formation.

Tx: Niacin
 hypolipoproteinemia
HYPOALPHALIPOPROTEINEMIA
TANGIER DISEASE (In homozygotes, HDL is as low
as 1-2 mg/dL)
Tx: Niacin

HYPOBETALIPOPROTEINEMIA
 lipid
&
lipoprotein
analyses
 px preparation
Fasting: 12-14 hrs
Fasting state: TAG is present in VLDL
Non-fasting state: in Chylomicrons
Posture: Px is recommended to be seated for 5mins.
before sampling to prevent hemoconcentration
 chole. measurement
1) Chemical Methods
 Dehydration & oxidation of Chole. to form a colored
compound
 BLOORS 2-step Mtd: Extraction + Colorimetry
 ABELL-KENDALL 3-step Mtd: Saponification + E + C
 LIEBERMANN-BURCHARDT (Green)
 Glacial HAC + Acetic anhydride + Conc. H₂SO₄
 Product: CHOLESTADIENYL MONOSULFONIC ACID
 SALKOWSKI (Red)
 Product: CHOLESTADIENYL DISULFONIC ACID
 chole. measurement
2) Enzymatic Methods
CHOLESTEROL OXIDASE REACTION
Interference: Ascorbic acid, hemoglobin, bilirubin

Reference Method: ABELL, LEVY & BRODIE MTD.

 TAG measurement
1) Chemical Methods
 VAN HANDEL & ZILVERSMITH (Colorimetric)
 + Chromotropic Acid = BLUE color compound
 HANTZCH CONDENSATION (Fluorometric)
 + Diacetyl Acetone + NH3 = DIACETYL LUTIDINE Compound

2) Enzymatic methods
 GLYCEROL
KINASE METHOD

Reference Method: MODIFIED VAN HANDEL & ZILVERSMITH METHOD

 Lipoprotein methodologies
1) ULTRACENTRIFUGATION (Reference Mtd.)
2) AGAROSE-GEL ELECTROPHORESIS
3) CHEMICAL PRECIPITATION
4) CHROMATOGRAPHIC METHODS
5) IMMUNOCHEMICAL METHODS
LDL-C = TC – HDL - VLDL
 Assignment!
1 whole sheet of paper. Handwritten.

1. Formula for getting the LDL value using:

 FRIEDEWALD METHOD
 DE LONG METHOD

2. FREDRICKSON CLASSIFICATION
15 mins…