plasma lipoprotein Flashcards
lipoproteins are — , — complexes of – and —
function is to transport — to and from — and to keep their lipid components – for transport in the plasma
- the types of lipoproteins are:
- Chylomicrons
- High Density Lipoproteins (HDL)
- Low Density Lipoproteins (LDL)
-Very Low Density Lipoproteins (VLDL)
structure:
1- — outer shel , — (—) ends are exposed on the surface making the particle —
2- — core
Core containing Neutral lipid core
Core containing — & —
obtained from the — or — synthesis
spherical and macromoluclar
lipids
specific proteins ( apolipoproteins)
lipids
tissue
soluble
amiphaltic
hydrophilic polar
soluble
neutral lipid
triglecyrole and chelstrol esters
diet or de nevo synthesis
lipoprotein density:
Lipoproteins differ in their density:
— < — < — < —
Less dense –> – lipid , — size
More dense –> – lipid , – size
NB: densities vary because lipoproteins — lipids in the circulation
chylomicrons < VLDL < LDL < HDL
more lipid larger size
less lipid smaller sixe
exchange
composition of plasma lipoprotein:
-The lipoprotein classes differ significantly in their — composition and — composition
-There is a high concentration of — and — in the low density lipoprotein (LDL)
lipid and protein
cholesterol and cholesterol esters
apoliporoteins:
Functions:
-essential — components
-non-essential structural components - —
- — for cell-surface receptors
- — for lipid metabolism enzymes
Five major classes:
Apolipoprotein A, B, C, D & E
Sub-classes exist also (eg: apo C-II, apo E2, E3,E4)
structural
transferable
ligands
coenzymes
chylomicrons and dietary lipid transport:
- Dietary fats & fat soluble vitamins are absorbed by the cells of the —
-They are transported to the rest of the body via the circulation in —
-Chylomicrons are synthesised in — cells & contain:
1- —-
2- —-
3- —
4- — : ~ 90%
intestinal mucosa Chylomicrons
intestinal mucosa
chlyomicrons
mucosal cells
cholesterol
cholesterol esters
fat soluble vitamins
triacylycerole
chylomicron metabolism:
1- — synthesis: Apolipoprotein B-48 is synthesised in the —-
2- — synthesis: of TG, cholesterol, phospholipids occurs in the —
3- — assembly: The Apo B-48 protein is loaded with lipid & moves into the – where chylomicrons are packaged into —
- ‘Nascent’ chylomicrons are secreted into the — & enter the —
4- — : Chylomicrons in the blood plasma receive additional — by exchange with – particles
-Apo C, inc. Apo C-II – activates —
- Apo E – recognised by – receptors
5- – of chylomicron TG by the tissues:
-Most tissues (not adult liver) have the enzyme
Lipoprotein Lipase (LPL) attached to the — (an — enzyme)
- LPL is activated by — & degrades – within the — releasing:
+ —– taken up by tissues for – as TG (adipose tissue) or
— production (muscle)
+ — – taken up by the –
6- — of ‘chylomicron remnants’:
-As – are removed, chylomicrons get — & more —
-They also lose — back to — : This forms the –
- Liver receptors recognise — on chylomicron remnants & clear them from circulation for breakdown - [Receptor-mediated –]
apolipoprotein
rough er
lipid
smooth er
chylomicron
golgi apparatus
secretory vesicles
lymphatic system
blood stream
maturation
apoliproteins
HDL
lipoprotein lipase
liver
utilisation
capillary walls
extracellular
Apo C-II
TG
chylomicrons
fattty acids
storage
energy
glycerol
liver
clearance
Tgs
smaller and more dense
Apo C
HD;
chylomicrons remnants
Apo E
endocytosis
transport of lipid sythesis in the body:
VLDL – transport of – synthesised —
LDL – transport of – synthesised –
HDL – transport of – from the – to the — aka ‘ — cholesterol transport’
endogenously
tg
endogenously
cholesterol
cholestrole
tissue
liver
reverse
VLDL metabolism:
- VLDL are produced in the – (~ 60% TG) by a process similar to chylomicron synthesis: [NB: Apo B-100 is the – protein]
- Secreted as — VLDL into the circulation, they pick up – &— from —
- TG contained in VLDL particles is degraded by — (similar to chylomicrons)
- As this happens, VLDL get – & — dense
liver
major
nascent
Apo C-ii and Apo E
from HDL
LPL
smaller and more dense
- VLDL become LDL through:
[a] Losing – & – back to—
[b] Exchanging lipids with—
TG + Phospholipid –> —
Cholesteryl ester –> —
- Catalysed by –
Apo C and E
HDL
HDL
HDL
VLDL
cholesterol esterase transfer protein (CETP)
LDL metabolism:
- LDL contain mostly – & —
-Their primary role is to deliver these to – or to carry them back to the —
-Delivery to the tissues (inc. liver) is by means of —
-This involves the LDL receptor:
recognises — (but not Apo B-48)
recognises –
The LDL particle is degraded —
-LDL, especially Oxidised-LDL, can be taken up also by —
-Macrophages express high levels of —
- This is very good at taking up LDL whose lipids and/or Apo B have been—
-The macrophages become engorged with — and transform into ‘–Cells’
-A key step in the formation of the —
cholstrole and cholesterol ester
peripheral tissues
liver
receptor-mediated endocytosis
Apo- b 100
Apo E
completly
macrophages
SR-A, the Scavenger Receptor class A
oxidised
ox-LDL
foam cells
atherosclerotic plaque
HDL metabolism:
HDL are formed in the – by addition of – to — , which is synthesised by – &— , and develop into – HDL
-Nascent HDL contain: — , –
- They accumulate — rapidly from – & other –
blood
lipids
apolipoprotein Apo A-1
liver and small intestine
nascent
Apo A , C , E and phospoulipid
cholesterol
cell membrane and lipoproteins
HDL roles:
[a] a — of apolipoproteins [Apo C-II, Apo E]
[b] accumulating unesterified —
[c] rapid — of cholesterol
[d] — cholesterol transport - Very Important
Cholesterol is carried back to the – for:
- conversion to —
- excretion in the —
- use in — synthesis
Inverse relationship between — [HDL] & —
HDL = ‘— cholesterol’
reservoir
cholesterol
esterification
reverse
liver
bile salts
bile
steroids
plasma and atherosclerosis
good
hyperlipidemaemia:
Interaction between — predisposition and—
Disorders of :
-VLDL & Chylomicrons → —
-Disorders of LDL –> —
-Disorders of HDL → –
-Combined Hyperlipidaemia
genetic and diet
hypertriglyceridaemia
hypercholestolaemia
tangier disease
Hypertriglyceridaemia aloneDisorders of VLDL & Chylomicrons:
Majority of cases: — genes acting together = modest excess circulating —
Some cases:
Familial hypertriglycerdaemia - underlying mutation not identified
Lipoprotein Lipase Deficiency (LPL): Lack metabolism of –
Apoprotein CII Deficiency: No — of LPL
= Persistence of—
multiple
tg
activation
chlymicrons
Hypercholesterolaemia aloneDisorders of LDL:
1- Heterozygous Familial Hypercholesterolaemia is —- 1:500
-Lack production of LDL receptor
-High plasma cholesterol, family history early cardiovascular disease, unresponsive to dietary treatment
2- Apoprotein B-100 gene mutations
Required for binding of LDL to receptor = — LDL concentrations in blood
3- Polygenic Hypercholesterolaemia
Remainder of population: Raised plasma cholesterol levels
Precise nature unknown
Maybe due to Apoprotein E variation
autosomal dominant
high
disorders of HDL :
1. Tangier disease
— - ABCA1 gene mutation
Low plasma HDL cholesterol concentrations Accumulation of cholesterol in tissues and arteries
Multiple symptoms including – disease
- Familial Autosomal Dominant HDL deficiency –
ABCA1 (or APOA1) gene mutation
Abnormalities of this gene contribute to low HDL levels in commonly seen CV disease
autosomal recessive
cv
Combined Hyperlipidaemia(Hypercholesterolaemia & Hypertriglyceridaemia):
Most common patient group
1- Polygenic: increased risk of – disease due to high – levels and suppression of HDL associated with High – levels
2- Familial Combined Hyperlipidaemia: High – and high – associated with family history
Common 1:200
Genetic basis not characterised
3- Remnant Hyperlipidaemia
Rare; 1: 5,000
Accumulation of remnant LDL particles
Inheritance of Apoprotein E2 variant combined with another primary Hyperlipidaemia
cv
ldl
tg
cholesterol and high tg
