LIPIDS o Forms:

▪ Cholesterol Ester (70%)— hydrophobic

• Triacylglycerol = Triglyceride = TAG — Compose of cholesterol ring and a FA
• Lipolysis = breakdown of TAG —> Glycerol + FA — Protective form for storage and transport,
• Gluconeogenesis = synthesis of new glucose from along with TAG
noncarbohydrate sources — Undergoes esterification by LCAT (Lecithin-
o Glycerol (3C) oxidized/converted to DHAP Cholesterol Acyl Transferase)
(dihydroxyacetone phosphate: 3C) and proceeds to — LCAT catalyzes the esterification of
glycolysis —> GA3P—> pyruvate—> Acetyl CoA —> Krebs cholesterol by promoting the transfer of FA
cycle from lecithin to cholesterol which results in
o FA (16C) is converted into CoA (2 carbon sequences) and the formation of lysolecithin and cholesterol
proceeds to Krebs cycle [β-oxidation] ester
• Lipogenesis = FA + Glycerol —> TAG ▪ Free (unesterified) (30%)— amphiphile
• Ketogenesis = Acetyl CoA —> Ketones — Found on the surface of lipoproteins/surface
• Cholesterol synthesis = Acetyl CoA —> Cholesterol of lipid layers along with phospholipids
o Cholesterol is important for bile salt production which is
essential for emulsification process and digestion of fat GENERAL LIPOPROTEIN STRUCTURE
o Cholesterol is also precursor to steroid hormones (e.g.,
• Large macromolecular complexes of lipids with specialized
corticosteroid hormones, estrogen, sex hormones, sex
protein (apolipoprotein)
androgens)
• Main purpose: transport of TAG and cholesterol to sites of
o Cholesterol important to cell membrane structure
energy storage and utilization
CHARACTERISTICS • HDL— highest protein content
• LDL— highest cholesterol content
• Fats • Chylomicron— highest exogenous TAG content
• Soluble in nonpolar organic solvents (e.g., chloroform and • VLDL— highest endogenous TAG content
ether) • General lipoprotein structure:
• Insoluble in polar solvents (e.g., water) o Hydrophobic core:
• Water insoluble, non-polar, transported by lipoproteins ▪ TAG
▪ Free FA
FORMS OF LIPIDS
▪ Cholesterol ester
A. Fatty Acids o Amphiphilic surface:
o Carboxyl group at the polar end (hydrophilic) ▪ Phospholipid monolayer
o Hydrocarbon chain at the nonpolar tail (hydrophobic) ▪ Proteins
o amphipathic ▪ Free cholesterol
B. Phospholipids/Phosphoacylglycerol • Lipoprotein classification:
o 2 esterified fatty acid o Buoyant density:
o Most abundant lipid in the body ▪ Separation of lipoproteins depends on the ratio
o Serves as surfactant between lipids and proteins content
o Forms: ▪ HDL (1.063-1.21 g/mL)
▪ Lecithin/Phosphatidyl choline (70%) ▪ LDL (1.019-1.063)
▪ Sphingomyelin (20%)— not derived from glycerol ▪ VLDL (0.93-1.006)
but from sphingosine ▪ Chylomicrons (< 0.93)
▪ Cephalin (10%) o Electrophoretic mobility:
C. Triglycerides ▪ Separation of lipoproteins are based on the
o AKA neutral fat (no charge) number of charges present on lipoproteins and
o 3 fatty acids attached to 1 glycerol are independent of their size and density
o Main storage of lipid in man (in adipose tissue) ▪ α-lipoproteins = HDL
o Low calorie intake = low TAG level ▪ pre-β-lipoproteins = VLDL
o Lipases: enzymes that hydrolyze the ester linkages of ▪ β-lipoproteins = LDL
TAG • Major Lipoproteins
D. Cholesterol A. Chylomicrons
o Unsaturated steroid alcohol containing 4 C rings o Largest and the least dense
o Precursor of 5 major classes of steroids: o Apolipoproteins
▪ Progestins— sex hormones ▪ apoB-48: unique to chylos
▪ Glucocorticoids— cortisol ▪ apoC-II: activator of lipoprotein lipase
▪ Mineralocorticoids— aldosterone ▪ apoE
▪ Androgens— sex hormones o Produced in the intestines (completely cleared
▪ Estrogen— sex hormones within 6-9 hours post prandial)
o found on the surface of lipid layers; synthesized in o Results in creamy/milky plasma— hallmark for
the liver the presence of chylomicrons
 o Principal role: o LpX formation associates with a high level of
▪ Transports exogenous TAG— from your diet hepatic cholesterol synthesis
▪ Delivery of dietary lipids to hepatic and D. β-VLDL
peripheral cells o floating β-lipoprotein
B. Very Low-Density Lipoproteins o Accumulates in type 3 hyperlipoproteinemia.
o Produced by the liver Uptake of cholesterol ester-rich β-VLDL by
o Also rich in TAG macrophages induces foam cell formation
o Apolipoproteins
▪ apoB-100: most common LIPOPROTEIN PHYSIOLOGY AND METABOLISM
▪ apoC-I, apoC-II, apoC-III, apoE A. Lipid Metabolism
o Principal role: o In digestion, dietary lipids are converted to
▪ Transports endogenous TAG (hepatic- amphipathic lipids
derived) to peripheral tissues o Amphipathic lipids form micelles in intestinal lumen
C. Low-Density Lipoproteins o Micelles come into contact with microvillus
o Consequence of the lipolysis of VLDL membranes of intestinal mucosal cells and are
o Bad cholesterol absorbed
o Apolipoproteins B. Exogenous Pathway
▪ ApoB-100: main constituent o Chylomicrons interact with proteoglycans on surface
▪ Traces of apoC of capillaries in various tissues in circulation
o Principal role o Free FA and glycerol from hydrolysis of TAG by
▪ Transports cholesterol from the liver to the lipoprotein lipase can then be taken up
peripheral tissue C. Endogenous Pathway
D. High-Density Lipoproteins o VLDL loses core lipids, causing dissociation and
o Smallest and heaviest LPP transfer of apolipoproteins and phospholipids to
o Produced by the liver and intestine other lipoprotein particles
o Can exist as either: o During this, VLDL is converted to VLDL remnants,
▪ Disc-shaped which can be further transformed by lipolysis into
— Nascent HDL (bilayer of PL + Proteins) LDL
— HDL takes free cholesterol from the cell o About half of VLDL is converted to LDL; remainder is
membranes taken up as VLDL remnants by liver remnant
— Once C is taken up, it is esterified by LCAT receptors
— After esterification, HDL becomes D. Reverse Cholesterol Transport Pathway
spherical o HDL removes excess cholesterol from cells
▪ Spherical particles
— Taken up by the liver and CE are LIPOPROTEIN METHODOLOGY
degraded
o Good cholesterol • Fasting— 12-14 hours
o Apolipoprotein • Required when TAG and LDL are being measured
▪ apoA-I: major apolipoprotein • Not required when TC and HDL are measured
o Principal role
▪ Removes cholesterol from the cells (reverse A. Cholesterol Measurement
cholesterol transport) 1. Chemical Methods
1.1 Abell-Kendall Method
• Minor Lipoproteins 1.2 Bloors Method
A. IDL 2. Enzymatic Method
o VLDL remnants 2.1 Cholesterol Oxidase Method
o Type III hyperlipoproteinemia
(dysbetalipoproteinemia or broad beta disease)
o Concentrations of IDL also contribute to the
development of CHD
B. Lp(a)
o Sinking pre-β lipoprotein
o LDL-like particles that contain one molecule of
apo(a) linked to apoB-100 by a disulfide bond
3. GC-MS Method (Reference method)
o The concentration of Lp(a) is inversely related to
B. Triglyceride Measurement
the size of the isoform
1. Chemical Method
o Increased levels confer increased risk for
1.1 Van Handel and Zilversmith Method
premature coronary heart disease and stroke
2. Enzymatic Method
C. LpX Lipoprotein
2.1 Glycerol Kinase Method
o Obstructive biliary disease and LCAT deficiency
 3. GC-MS (Reference method)
C. High-Density Lipoprotein Methods
1. Precipitation Method (Routine method)
▪ ApoB containing LP are removed by precipitation
with polyanions and cholesterol is measured in
the HDL-containing supernate
▪ Polyanions
Heparin + MgCl2
Sodium tungstate + MgCl2
Dextran + MgCl2
2. Magnetic Method
▪ Similar to HDL-C precipitation method but uses a
precipitant that is complexed to magnetic
particle
3. Homogenous Method (Direct method)
3.1 Enzymatic Method
Use antibodies to apoB LP to make them
non-reactive

3.2 Three-Step Method (Reference method)

(1) Ultracentrifugation
(2) Precipitation of apoB-containing LP
(3) Measurement of cholesterol in the
supernatant using the Abell-Kendall assay

D. Low-Density Lipoprotein Methods

1. Indirect Method
1.1 Friedewald Equation (Routine method)
Inappropriate for TG > 400 mg/dL ( ̴ 4.5
mmol/L)
LDL = TC – (vLDL + HDL)
vLDL (mg/dL) = TAG/5
vLDL (mg/dL) = TAG/2.2
1.2 Beta Quantitation (Reference method)
Sample: plasma
Two-step procedure
(1) Ultracentrifugation to remove vLDL
(2) Chemical precipitation of HDL-C
(3) Computation: LDL = TC- HDL-C
2. Direct Method
2.1 Selective Precipitation
2.2 Homogenous Method (third generation)
Cholesterol is not readily catabolized by most cells, and therefore,
does not serve as a source of fuel. It can only be stored if in excess
sila

HDL— indirect marker of atherosclerosis

LDL— direct marker of atherosclerosis