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LIPIDS AND LIPOPROTEINS

o 10 BILE ACIDS
Cholic acid
Chenodeoxycholic acid:
detergents
o STEROID HORMONES
Adrenal
Testis
Ovary
o VITAMIN D3
Irradiation of skin

Four Major Lipids

Phospholipids
Fatty Acids
Triglycerides
Cholesterol

PHOSPHOLIPIDS

Contain TWO FA and a


PHOSPHOLIPID HEAD group
Amphipatic (hydrophobic and

hydrophilic ends)
Main component of lipid bilayer

FATTY ACIDS

LINEAR chains of C-H bonds that


terminate with a carboxyl group (COOH)

Types of FA:
o Saturated
o Monounsaturated
o Polyunsaturated
TRIGLYCERIDES

Contain THREE FA attached to one


molecule of GLYCEROL
SOLID: Saturated FA from animals

LIQUID: Unsaturated FA from plants

CHOLESTEROL

Unsaturated steroid alcohol

containing FOUR RINGS and a SINGLE


C-H side chain
HYDROPHOBIC in nature, except on

the HYDROXYL part of the A-RING


AMPHIPATIC: found on the

SURFACE of lipid layers


ESTERIFIED FORM: CHOLESTERYL
ESTER (hydrophobic)

Converted to:

LIPOPROTEINS

Composed of lipids and proteins

(APOLIPOPROTEINS)
SURFACE: amphipathic (P and C)

CORE: hydrophobic (T and CE)

*Lipid content = larger core region =


lighter density

Chylomicrons
VLDL
LDL
HDL

APOLIPOPROTEINS

CHON components of lipoproteins


Maintains structural integrity of

lipoproteins
LIGANDS for cell receptors
Activators and inhibitors of enzymes

With AMPHIPATHIC HELIX


o Protein segments in coils
accounting to the ability to
bind to lipids

Apo A1
Apo B (Apo B-100 and Apo B-48)
Apo C (I, II, III)
Apo E (Apo E2, E3 and E4): affects
lipoprotein metabolism

MAJOR ENZYMES OF CLINICAL


SIGNIFICANCE
ENZYME
Acid phosphatase
(ACP)
Alanine
aminotransferase
(ALT)
Aldolase (ALD)
Alkaline
phosphatase (ALP)
Amylase (AMS)
Angiotensinconverting enzyme
(ACE)
Aspartate aminotransferase (AST)

Chymotrypsin (CHY)
Creatinine kinase
(CK)
Elastase-1 (E1)
Glucose-6phosphate
dehydrogenase (G6-PD)
Glutamate
dehydrogenase
(GLD)
glutamyltransferase
(GGT)
Glutathione-Stransferase (GST)

CLINICAL
SIGNIFICANCE
Prostatic Carcinoma
Hepatic Disorder

Skeletal Muscle
Disorder
Hepatic Disorder
Bone Disorder
Acute pancreatitis
Blood Pressure
regulation
Myocardial
infarction
Hepatic Disorder
Skeletal Muscle
Disorder
Chronic pancreatitis
insufficiency
Myocardial
Infarction
Skeletal Muscle
Disorder
Chronic Pancreatitis
Insufficiency
Drug induced
hemolytic anemia

Glycogen
phosphorylase (GP)
Lactate
Dehydrogenase
(LDH)

Myocardial
infarction
Hepatic Disorder
Hemolysis
Carcinoma
Lipase (LPS)
Acute Pancreatitis
5-Nucleotidase
Hepatic Disorder
Pseudocholinesterase Organophosphate
poisoning
(PChE)
Genetic variants
Hepatic Disorder
Suxamethonium
sensitivity
Pyruvate Kinase
Hemolytic anemia
(PK)
Trypsin (TRY)
Acute Pancreatitis
CHYLOMICRONS

Largest and the least dense

(1200nm)
Account to the turbidity of post

Hepatic Disorder

prandial plasma
Readily FLOAT on top of plasma
(creamy layer)
Deliver dietary lipids to hepatic and
peripheral cells

VERY LOW DENSITY LIPOPROTEINS


(VLDL)

CARRIERS OF ENDOGENOUS

TRIGLYCERIDES
Transfer TG from the liver to the
periphery

Hepatic disorder

Hepatic disorder

Acute myocardial
infarction

Causes turbidity in fasting


hyperlipidemic plasma

Increases
o Diet CHO, Sat. FA
o Hepatic synthesis of TG
o VLDL

LOW DENSITY LIPOPROTEINS (LDL)

More cholesterol rich


Formed due to lipolysis of VLDL

PROARTHEROGENIC LIPOPROTEIN

Important Enzymes:

LPL (lipoprotein lipase)

LCAT (Lecithin-cholesterol

acetyltransferase)
ACAT (acyl-CoA: Cholesterol Acyl

Transferase)
HMG CoA reductase (3-hydroxy-3-

HIGH DENSITY LIPOPROTEIN (HDL)

SMALLEST and MOST DENSE


lipoprotein
Synthesized by both liver and
intestines

Delivers lipids to the liver


With ANTIATHEROGENIC property
Discoidal (most active form) or
spherical (HDL2 and HDL3)

methyl-glutaryl-CoA reductase)
CHOLESTEROL MEASUREMENT
1. Enzymatic Method: Cholesterol
Oxidase and Esterase
2. Non-enzymatic: LiebermannBurchard

MINOR LIPOPROTEINS
Lipoprotein A

ABELL KENDALL

LDL-like particles
Confer increased risk of CHD and stroke
HOMOLOGOUS to plasminogen
o Compete for binding sites
o Promotes clotting = Myocardial

cholesterol with
petroleum ether

Intermediate Density Lipoprotein


Formed from catabolism of VLDL

Precursor for LDL synthesis

LIPOPROTEIN METABOLISM
1. EXOGENOUS LIPOPROTEINS
(Chylomicrons)
2. ENDOGENOUS LIPOPROTEINS (VLDL,
HDL)
3. Chylomicrons TG = chylomicron
remnants
4. VLDL TG = LDL

HYDROLYSIS with KOH


Extraction of
unesterified

Infarction

Cholesterol +H2SO4 + acetic


anhydride = green solution

Measurement using L-B


reaction

TRIGLYCERIDE MEASUREMENT
1. Enzymatic Method:
GLYCEROL KINASE (Lipase,

GK, PK, LD)


Disappearance of NADH at
340 nm

2. Non-enzymatic:
Extraction of lipids using
chloroform

A. VAN HANDELL AND

Determination of LDL-C

ZILVERSMITH

LDL-C = TC (HDL + VLDL)


o Friedwald Equation

Hydrolysis with KOH


(Glycerol + FA)
Formaldehyde +
chromotropic (blue
solution)

VLDL = TG / 5 (mg/dL)
VLDL = TG / 2.175
(mmol/L)

o De Long Equation:
B. HANTZCH CONDENSATION
(Fluorometric Method)
Hydrolysis with KOH
(glycerol + FA)
Glycerol + PA
(formaldehyde)
Formaldehyde +
acetylacetone + NH3
(YELLOW)

VLDL = TG / 6.5 (mg/dL)


VLDL = TG / 2.825
(mmol/L)

Determination of Chylomicrons

STANDING PLASMA TEST


o Sample refrigerated
OVERNIGHT at 40C
o Chylomicrons appear as
floating cream

ESTIMATION OF LIPOPROTEINS
1. Ultracentrifugation:
o Based on MOLECULAR
DENSITY
o LIGHTEST to HEAVIEST
(Chylomicrons, VLDL, LDL,
HDL)

CLINICAL CORRELATIONS
Dyslipidemia: abnormal lipid concentration

2. Electrophoresis

o MIGRATION in electrical field


o Stains
o 4 Bands
, Pre-, , chylomicrons
3. Polyanion Precipitation
o Based on PARTICLE SIZE,
CHARGE and
APOLIPOPROTEIN CONTENT
o Heparin SO4, dextran SO4,
phosphotungsten with Ca2+,
Mg2+, Mn2+

Atherosclerosis
Myocardial infarction
Hypertension
Hyperlipoproteinemia (hyperchole,
hyperTG)
Lp (a) elevations
Hypolipoproteinemia
o Abetalipoproteinemia
(BASSEN-KORNZWEIG
SYNDROME)
o Hypoalphalipoproteinemia
(TANGIERS DISEASE)

Hyperlipoproteinemia
TYPE LIPOPROTEIN

APPEARANCE
OF PLASMA

Chylomicrons

Creamy Layer
over clear
plasma

IIA

LDL

IB

LDL,

III

-VLDL

Turbid

IV

VLDL

Turbid to milky

VLDL
chylomicrons

Creamy layer
over turbid

clear
VLDL

Slightly turbid

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