• A lipoproteinis a biochemical assembly whose purpose is to
transport hydrophobic lipid(a.k.a. fat) molecules in water,
as in blood or extracellular fluid.
• They have a single-layer phospholipid and cholesterol outer
shell, with the hydrophilic portions oriented outward toward
the surrounding water and lipophilic portions of each
molecule oriented inwards toward the lipids molecules
within the particles.
3.
• Apolipoproteins areembedded in the membrane, both stabilising the
complex and giving it functional identity determining its fate
• Thus the complex serves to emulsify the fats.
• Many enzymes, transporters, structural proteins, antigens, adhesions, and
toxins are lipoproteins. Examples include the plasma lipoprotein particles
classified as HDL, LDL, IDL, VLDL and ULDL (a.k.a. chylomicrons)
lipoproteins, according to density / size (an inverse relationship), compared
with the surrounding plasma water.
4.
• These complexprotein capsules enable fats to be carried in all
extracellular water, including the blood stream (an example of
emulsification), subgroups of which are primary drivers / modulators
of atherosclerosis,[1] the transmembrane proteins of mitochondrion,
chloroplast, and bacterial lipoproteins.
• Proteolipids are a different kind of protein-lipid combination that are
insoluble in water.
• Proteolipids are abundant in brain tissue, and are also present in many
other animal and plant tissues.[3]
5.
Function
• The handlingof lipoprotein particles in the body is referred to as lipoprotein particle
metabolism. It is divided into two pathways, exogenous and endogenous, depending
in large part on whether the lipoprotein particles in question are composed chiefly
of dietary (exogenous) lipids or whether they originated in the liver (endogenous),
through de novo synthesis of triacylglycerols.
• The hepatocytes are the main platform for the handling of triacylglycerols and
cholesterol; the liver can also store certain amounts of glycogen and
triacylglycerols.
• While adipocytes are the main storage cells for triacylglycerols, they do not
produce any lipoproteins.
6.
TYPES OF LIPOPROTEIN
1.LDL :- Low density lipoprotein ,highest in cholesterol esters as % of weight.
2. HDL:- High density lipoprotein ,highest in density due to high protein
/protein ratio .
3. CHYLOMICRON :- Largest ,lowest in density due to high lipid/protein
ratio: highest in triacylglycerols as % of weight.
4. VLDL:- Very low density lipoprotein : 2nd highest in triacylglycerols as % of
weight .
5. IDL:- Intermediate density lipoprotein.
METABOLISM OF LDL
•About 40 to 60% of all LDL are cleared by the liver in a
process mediated by apo B and hepatic LDL receptors.
• The rest are taken up by either hepatic LDL or non-hepatic
non-LDL (scavenger) receptor.
11.
FUNCTION OF LDL
•These particles are remodeled at the liver and transformed into LDL.
• The function of LDL is to deliver cholesterol to cells ,where it is used
in membranes ,or for the synthesis of steroid hormones(blue
pathway).
• Cells take up cholesterol by receptor mediated endocytosis .
12.
• Are theprinciplecholesterol and for transfer in human blood that
carries cholesterol from the liver to the body tissues and cells.
• Appopriate levels of LDL cholesterol can positively impact health in
many ways.
• Raised plasma levels of LDL are linked to an increased risk for
disease.
• Hdl typeis the smallest of the lipoprotein particles.
• It is the densest because it contain the highest proportion of protein to
lipid .
• Its most abundant apolipoproteins.
15.
FUNCTION OF HDL:
• High density lipoprotein (HDL) particles are
protective particles that have functions in the body .
• Play a key role in protecting against heart disease via
their role in reverse cholesterol transport , or the
transport of excess cholesterol out of the body.
16.
Metabolism of HDL:
• HDL are synthesized in the liver and the small intestine .
• They are the lipoprotein with the higher protein content (it can reach around 50%
of the particle total weight).
• When secreted they contain little cholesterol and no cholesteryl esters.
• HDL are formed by different apolipoproteins ,including apo A1, apoe and apo C-II.
• In fact ,they act as transporters of apoe and apo C-II from their synthesizing organ
to the plasma, making availablae these apoproteins to other lipoproteins.
17.
• Apo A-1is the main protein in HDL ,and activates LCAT , enzyme
associated to HDL.
• Phopholipids are the main lipidic content of HDL (35% of the total weight )
and the enzyme lecithin cholesterol acyl transsferase (LCAT) catalyze the
transfer to acyl groups (fatty acids esterifies to lecithin ) from lecithin to
cholesterol scavenged from cell member of extrahepatic tissues, and from
IDL and chylomicron remnants , producing cholesterol esters ,that are
dissolve in the HDL core ,so these lipoprotein become the cholesterol rich
HDL2 and HDL3.
METABOLISM OF CHYLOMICRON
•The enzyme lipoprotein lipase with apolipoprotein
(apo) C-II as a co-factor ,hydrolyzes chylomicron
triglyceride allowing the deliver of free fatty acids to
muscle and adipose tissue.
22.
• As aresult ,a new particle called a chylomicron remnant is formed.
• This particle is enriched in cholesteryl ester fat-soluble vitamins and contains
apoB-48 and apoE.
• It is rapidly removed from the circulation by the liver .
• ApoE is the moiety required for rapid hepatic removal.
• Its activity is inhibited by C apolipoproteins , especially apoC-I
FUNCTION OF VLDL
•Vldl transports endogenous triglycerides ,phospholipids ,cholesterol
and cholestrylesters.
• It functions as the body’s internal transport mechanism for lipids .
• In addition it serves for long range transport of hydrophobic
intercellular messengers ,like the morphogen .
LIPOPROTEIN INTERPRETATION
• Levelshigher than 10 mg/dl are associated with an increase in
cardiovascular risk .
• The apolipoproteins have a primary responsibility for the transports of
lipids and cholesterol .
• Apolipoprotein B is a nonexchangeable lipoprotein that exists in two
forms in humens ,apoB-100 and apo-48 .
33.
Estimation of lipoprotein
Polyanionprecipitation :
• Lipoprotein are precipited with polyanions ( heparin sulphate , dextran
sulphate and phosphotungstate )
• Reaction should be in the presence of divalent cations Mg,Ca, and Mn.
• Most commonly for HDL and is reasonably specific.
34.
LIPOPROTEIN ELECTROPHORESIS
• Usedto identify rare familial disorder
• Indication :-
• Serum TG>300 mg/dl
• Fasting serum is lipemic.
• Significant hyperglycemia , impaired glucose intolerance .
• Serum uric acid >8.5 mg/dl.
• Clinical evidence of CHD or atherosclerosis in patient <40 years of age.