lipoproteins Flashcards
what are lipoproteins
Phospholipids, triglycerides, cholesterol,
and cholesteryl esters can be packaged
with proteins into a hydrophilic (or “water
loving”) macromolecule complex called a
lipoprotein
what is the structure of a lipoprotein
Triglycerides and
cholesteryl esters reside
in the lipoprotein core
* Phospholipids (PL) form a
monolayer: the phosphate
group interacts with the
aqueous phase and acyl
chains interact with the
lipoprotein core
* Cholesterol is embedded
in the PL monolayer with
the –OH exposed to the
aqueous phase
* Apolipoproteins are
embedded in the PL
monolayer
what are the classes of lipoproteins
- VLDL = very low-density
lipoprotein - LDL = low-density
lipoprotein - HDL = high-density
lipoprotein
what is the function of chylomicrons
deliver triglycerides from
the intestines that are derived from food
intake
what is the function of VLDL
deliver triglycerides derived from
the liver to non-hepatic tissue
what is the function of LDL
deliver cholesterol and cholesteryl
esters derived from the liver to non-hepatic
tissues
what is the function of HDL
removes excess cholesterol from
non-hepatic tissues
what is IDL
intermediate between VLDL and LDL
generated via TG hydrolysis by LPL
what are chylomicron remanents
TG-depleted,
cholesterol-enriched chylomicrons
generated via TG hydrolysis by LPL
what are B-VLDL
TG-depleted,
cholesterol-enriched VLDL with ‘beta
migration’, generated via TG hydrolysis by
LPL
what is a trend found within lipoproteins
they density is inversely proportional to thier size
what are the subclasses of VLDL
VLDL 1 and VLDL 2
what are the subclasses of LDL
LDL and sdLDL
what are the subclasses of HDL
preβ-HDL, HDL1, HDL2, HDL3, HDL4
– HDL2: HDL2a and HDL2b
– HDL3: HDL3a, HDL3b, HDL3c
how are lipoproteins named
Nomenclature is complex and based on
the different methods of separation:
– Density;
– Size;
– Electrostatic charge;
– Protein composition
where is ApoB100 HDL synth
in the liver
what makes lipoprotein X (LpX) different from other LDLs
it doesnt have ApoB100
what is LpX
a “LDL” found in
cholestasis and LCAT deficiency:
– Lamellar structure
* Spherical: 30-70 nm dia
what is the lipid content of LpX
- 66% phospholipid
- 22% cholesterol
- 6% protein – albumin in core & apoC’s on surface
- 3% cholesteryl esters
- 3% triglycerides
separatino of lipoproteins by electrostatic charge
Chylomicrons have no charge and
remain at the origin.
LDL migrates with β-macroglobulin
and is thus named a β-migrating
lipoprotein
VLDL migrates before
β-macroglobulin and is thus named
a preβ-migrating lipoprotein
HDL migrates with α-macroglobulin
and is thus named an α-migrating
lipoprotein.
what are a-migrating lipoproteins
HDL 1, HDL2, HDL3, HDL4
what are preB-migrating lipoproteins
VLDL, preβ-HDL
what are B-migrating lipoproteins
LDL, β-VLDL, chylomicron
remnants
what lipoproteins are found at the origin
chylomicrons
what are y-migrating lipoproteins
apoE-only HDL
what lipoproteins are found between the origin and b-migrating
LpX and
Lp(a)
what is another class of lipoproteins
lipoprotein (a) Lp(a)
lipoproteins obtained by affinity
chromatography for apoB would be named
LpB
lipoproteins separated by protein content
affinity chromatography for apolipoproteins
what are some physical properties of lipoproteins
- Density is directly proportional with
percent protein content and percent
phospholipid content - Density is inversely proportional with
triglyceride content
what are some protperties of HDL subclasses of lipoproteins
- Density is directly proportional with
percent protein content - Density is inversely proportional with size,
PL content, CE content, TG content, and
FC content
apolipoprotein
apo): a protein that is
void of lipid that can associate with
lipoproteins
how many and roughly what are the types of lipoproteins
- There are close to 200 known proteins that
can associate with lipoproteins:
– some have functions associated with
lipoprotein metabolism
– some just hitch a ride to be delivered to
tissues
non exchagneable versus exchangeable apolipoproteins
- ApoB48 & apoB100 NEVER fall off a
lipoprotein; they are non-exchangeable - All other apo’s can fall off a lipoprotein;
they are exchangeable
synthesis of VLDL
two step model
- The synthesis of VLDL occurs in the liver:
– Requires apoB100, lipids (TG, PL, FC, CE), &
microsomal triglyceride transfer protein (MTP)
– Occurs co-translationally/co-translocationally
– Slow process: 20 minutes for one VLDL
ApoB-100 vs. apoB-48
- ApoB-48 = 48% of the apoB-100 protein
(…apoB-100 = 100%) - ApoB-48 is generated in the intestine
through the enzymatic removal of an
amine group (‘deamination’) from a
specific cytidine on the mRNA sequence
for apoB-100 to generate uracil
– this introduces a stop codon ~48% into the
apoB-100 mRNA sequence
apoBs
ApoB’s act as integral proteins that
maintain the structure of chylomicrons,
VLDL, IDL, and LDL
– Both apoB’s are huge proteins
– Both apoB’s wrap around its lipoprotein
what differs apob48 from apob100 and vice versa
Only one apoB-48 is present on a
chylomicron, and only one apoB-100 is
present on VLDL, IDL, or LD
explain the apoB cotranslational/cotransolational synth
- The apoB mRNA is translated in the
cytosol into protein - During apoB protein synthesis, the
growing peptide is translocated from the
cytosol into the endoplasmic reticulum –
aka start of the cell secretory pathway - The packaging of lipids with apoB occurs
simultaneously as the protein is being
translated and translocated
what is MTP
Microsomal triglyceride transfer
protein (MTP)
what is the function of MTP
- MTP plays a critical role in the first step of VLDL synthesis
- MTP transfers stored triglycerides, as well as some phospholipids and cholesteryl
esters, to apoB:
– This occurs during apoB translocation and also during apoB100 transport through the endoplasmic reticulum
what happens in the absense of MTP
The absence of MTP prevents VLDL
synthesis and leads to apoB degradation
what is TGH
triacylglycerol hydrolase
what ist he function of TGH
- TGH hydrolyses triglycerides stored in
large cytosolic lipid droplets into glycerol
and three fatty acids
what happens to the TGH hydrolyisis products
- The hydrolysis products are liberated from the lipid droplets into the cytosol, where they are used toward re-synthesizing triglycerides
what is the fate of the newly synth TG
- The newly synthesized triglycerides are
thought to form their own small sized lipid
droplet - This small lipid droplet is incorporated as a
whole with VLDL 2 to yield a larger sized
VLDL 1
Targets currently being
investigated to lower VLDL/LDL
- ApoB100 synthesis
- Microsomal triglyceride transfer protein
(MTP) - Phosphatidic acid phosphatase (PAP),
also known as lipin-1
