LIPIDS AND

LIPOPROTEINS
Annabel M Laranjo, MD,FPCP,DPSMID
September 19-23, 2016
 Definition
• Lipids/fats – fatty acids, phospholipids,
cholesterol and cholesterol esters

• LPs-transport proteins for lipids

LIPIDS
Lipid droplet
Classification
Classification of lipids according
to function
 A. Fatty acids (R-COOH)
Saturated FA
• All single bonds
Unsaturated FA
• Monounsaturated-
single double bond
between any 2
carbons
• Polyunsaturated- 2 or
more double bonds
 B. Glycerol esters
1.Triacylglycerol(TAG) – are lipids that
combine FA to 3 carbon atoms of the
glycerol backbone
 B. Glycerol esters
2.Phosphoglycerides/
phospholipids-
glycerol esters that
contain phosphoric
acid group on one of
the end carbons of
the glycerol backbone
 Role of Phospholipids
• Major component of the
cell membrane
structure (lipid bilayer)
• Important ingredient of
LP coat essential for
secretion and transport
of plasma LP
molecules
• Essential component of
myelin sheath
(membrane that
surrounds the nerve
fiber)
 C. Sterols
• Complex lipids derived from the tetracyclic
solid alcohol known as “ cholesterol”
• Cholesterol and its esters are the basis of
the bile acids, steroid hormones and
vitamin D
 Function of Cholesterol
• Structural component of cell membrane
• Precursor for the synthesis of all other
steroids in the body
• Essential ingredient in the structure of LPs
• FA are transported to liver as cholesteryl
esters for oxidation
 Medical importance of
Cholesterol
• Exclusively synthesized by animals
• Not readily catabolized by most cells,
hence does not serve as a source of fuel
• Vehicle for uptake in tissues: LDL
• Vehicle for transport: HDL
• Major constituents of GALLSTONE
 Lipoproteins (LPs)
• Constitutes the body’s “petroleum
industry”
• Chylomicrons- carry dietary triglycerides
throughout the circulatory systems to cells
• Docking in the liver to deposit the
chylomicron remnants
Structure of Lipoprotein
Classification of LPs
Electrophoretic mobility of LPs
 Functions of LPs
• Chylomicrons- transporter of dietary lipids

• VLDL – carries TG and assembled in the

liver for energy needs and storage of fat

• LDL- deliver cholesterol to the peripheral

cells after the TG have been off loaded
 Function of LPs
• HDL –”good cholesterol”, clean-up crew
gathering up extra cholesterol for transport
back to the liver
DIGESTION OF LIPIDS
 Metabolism of Lipids
• Intraluminal phase/ digestive phase
– Dietary fats are modified both physically and
chemically before absorption
• Cellular phase/Absorptive phase
– The digested materials enters the intestinal
mucosal cells
• Transport phase
– Carried to other tissues through the lymphatics
Organs involved in digestion of
Lipids
Formation and fate of LPs
 Apolipoproteins
• Lipid-binding protein components of
plasma LPs
• Amphiphatic properties
– Solubilize the hydrophobic lipid constituents of
LPs
• Function as enzyme co-factors and
receptor ligands
 Types of Apolipoprotein
• Apo AI, apoAI and apo CI are responsible
for the removal of free cholesterol from
the extrahepatic tissues
• Apo B-48 and Apo B-100
• Apo E – regulates lipids by receptor
mediated uptake and clearance and
stimulation of lipolysis
Types of Apolipoprotein
Clinical Significance of
Lipid Metabolism
Fatty Liver
 Fatty Liver
• Abnormal accumulation of triglycerides
inside the liver cells
• Hepatic TAG synthesis provides the
immediate stimulus for the formation and
secretion of VLDL
• Impaired VLDL formation or secretion
leads to non-mobilization of lipid
components from the liver
 2 categories of Fatty Liver
• Non alcoholic fatty liver (NAFL)
– Increase synthesis of triglycerides:
– High carbohydrate diet
– High fat feeding
– Starvation
– Diabetes mellitus
 Alcoholic Fatty Liver
• Leads to fat accumulation in the liver and
ultimately cirrhosis
• Combination of impaired FA oxidation and
increased lipogenesis that is due to changes
in NADPH/NAD redox potential in the liver
• Interference with the action of transcription
factors regulating the expression of the
enzymes involved in pathways
 Lipid Storage
disease/Lysosomal
Storage disease
(Spingolipidosis)
 Lysosomal Storage disease
• Rare inherited disorders characterized by
the accumulation of undigested or partially
digested macromolecules which ultimately
results in cellular dysfunction and clinical
abnormalities
• Encompassed enzyme deficiencies of the
lysosomal hydrolases
Krabbe Disease
Gaucher’s Disease
Nieman-Pick Disease
Tay-Sach’s Disease
 Tay-Sach’s Disease
• Cherry-red spot in
the retina
– Hallmark
• Accumulation of
GM2 ganglioside
in the retina and
nerve cell
Primary Disorders of
Plasma Lipoproteins
 Dyslipoproteinemia/
Hyperlipoproteinemia
• Inherited defects of LP metabolism (hypo-
or hyperlipoproteinemia)
• Secondary abnormal LP patterns (DM,
hypothyroidism, NS, atherosclerosis)
• Due to defect at a stage in LP formation,
transport or degradation
 Xanthoma
• Yellow patch nodules in the skin cause by
deposition of lipids/fats
 Name Defect Characteristics
Familial LP Lipase Hypertriacylglycerolemia Slow clearance of
deficiency(Type 1) due to deficiency of LPL , chylomicrons and VLDL
abnormal LPL, or Apo C-
II deficiency causing Increased abnormal
inactive LPL chylomicrons & TG
“xanthomatosis”
Familial Defective LDL receptors Elevated LDL levels and
hypercholesterolemia or mutations in ligand hypercholesterolemia
(type IIa) region of apoB-100 resulting in
atherosclerosis and
coronary disease
Familial type III Deficiency in remnant Increase in chylomicron
hyperlipoproteinemia clearance by the liver is and VLDL remnants
(broad beta disease, due to abnormality in apo
familial E Causes:
dysbetalipoproteinemia ) hypercholesterolemia,
xanthomas, and
atherosclerosis
 Name Defect Characteristics
Homozygous for apo-E2 Normal chylomicron and Increase cholesterol and
VLDL synthesis with TG, low LDL
accumulation of
chylomicron remnants
Familial Overproduction of VLDL High cholesterol, VLDL,
hypertriacylglycerolemia will decreased VLDL subnormal LDL and HDL
(type IV) clearance

Relatively more common

a)Primary Often associated with Associated with
b)Secondary (drug glucose intolerance and alcoholism, DM and
therapy like estrogen, hyperinsulinemia obesity
alcohol abuse, glycogen
storage dse, obesity, DM
nephropathy)

Hepatic lipase deficiency Deficiency of the enzyme Patients have xanthomas

leads to accumulation of and coronary heart
large triacylglycerol-rich disease
HDL and VLDL remnants
Tangier Disease-absent HDL

• low HDL
• Low total
cholesterol
• Normal to slightly
increase TG
• Undetectable HDL
 Arteriosclerosis
• Deposition of lipids mainly esterified
cholesterol esters in the artery walls which
starts as thin layers called FATTY
STREAKS → cholesterol plaques that
particularly block blood flow
Mechanism of Plaque formation
 Risk for Fatty streak/Plaque
formation
• Chronic endothelial injury (like smoking)

• Hyperlipidemia
 Diseases associated with
arteriosclerosis
• Peripheral vascular disease (PVD) – arms
and legs
• Coronary artery disease (CAD) – eg
Myocardial infarction
• Cerebrovascular disease (CVD) – cerebral
vessels eg Stroke
 Risk factors in developing
arteriosclerosis
Non-modifiable Modifiable
• Gender • Hypertension

• Age • Cigarette smoking

• Family history (genetics) • Obesity/hyperlipidemia

• Diet

• Physical inactivity
 Primary goal of testing:
• to predict potential risk of Coronary Artery
Disease
 Lipid profile
• Total cholesterol
• HDL
• Apo A and Apo B
• Triglyceridess
• Increased risk:
– increase LDL and total cholesterol, decrease
HDL
• Decreased risk:
– Increase HDL
Appearance of serum/plasma left undisturbed for
4-6 hrs at 4-8C in hyperlipidemic patients

• Creamy layer indicates:

1. non-fasting specimens
2. Serious defects in LP production or function
• Lipemia
– varying degrees of cloudiness associated
with elevated TG
Thank You