lipoproteins Flashcards

1
Q

what are lipoproteins

A

Phospholipids, triglycerides, cholesterol,
and cholesteryl esters can be packaged
with proteins into a hydrophilic (or “water
loving”) macromolecule complex called a
lipoprotein

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2
Q

what is the structure of a lipoprotein

A

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

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3
Q

what are the classes of lipoproteins

A
  • VLDL = very low-density
    lipoprotein
  • LDL = low-density
    lipoprotein
  • HDL = high-density
    lipoprotein
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4
Q

what is the function of chylomicrons

A

deliver triglycerides from
the intestines that are derived from food
intake

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5
Q

what is the function of VLDL

A

deliver triglycerides derived from
the liver to non-hepatic tissue

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6
Q

what is the function of LDL

A

deliver cholesterol and cholesteryl
esters derived from the liver to non-hepatic
tissues

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7
Q

what is the function of HDL

A

removes excess cholesterol from
non-hepatic tissues

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8
Q

what is IDL

A

intermediate between VLDL and LDL
generated via TG hydrolysis by LPL

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9
Q

what are chylomicron remanents

A

TG-depleted,
cholesterol-enriched chylomicrons
generated via TG hydrolysis by LPL

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10
Q

what are B-VLDL

A

TG-depleted,
cholesterol-enriched VLDL with ‘beta
migration’, generated via TG hydrolysis by
LPL

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11
Q

what is a trend found within lipoproteins

A

they density is inversely proportional to thier size

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12
Q

what are the subclasses of VLDL

A

VLDL 1 and VLDL 2

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13
Q

what are the subclasses of LDL

A

LDL and sdLDL

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14
Q

what are the subclasses of HDL

A

preβ-HDL, HDL1, HDL2, HDL3, HDL4
– HDL2: HDL2a and HDL2b
– HDL3: HDL3a, HDL3b, HDL3c

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15
Q

how are lipoproteins named

A

Nomenclature is complex and based on
the different methods of separation:
– Density;
– Size;
– Electrostatic charge;
– Protein composition

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16
Q

where is ApoB100 HDL synth

A

in the liver

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17
Q

what makes lipoprotein X (LpX) different from other LDLs

A

it doesnt have ApoB100

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18
Q

what is LpX

A

a “LDL” found in
cholestasis and LCAT deficiency:
– Lamellar structure
* Spherical: 30-70 nm dia

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19
Q

what is the lipid content of LpX

A
  • 66% phospholipid
  • 22% cholesterol
  • 6% protein – albumin in core & apoC’s on surface
  • 3% cholesteryl esters
  • 3% triglycerides
20
Q

separatino of lipoproteins by electrostatic charge

A

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.

21
Q

what are a-migrating lipoproteins

A

HDL 1, HDL2, HDL3, HDL4

22
Q

what are preB-migrating lipoproteins

A

VLDL, preβ-HDL

23
Q

what are B-migrating lipoproteins

A

LDL, β-VLDL, chylomicron
remnants

24
Q

what lipoproteins are found at the origin

A

chylomicrons

25
what are y-migrating lipoproteins
apoE-only HDL
26
what lipoproteins are found between the origin and b-migrating
LpX and Lp(a)
27
what is another class of lipoproteins
lipoprotein (a) Lp(a)
28
lipoproteins obtained by affinity chromatography for apoB would be named
LpB lipoproteins separated by protein content affinity chromatography for apolipoproteins
29
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
30
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
31
apolipoprotein
apo): a protein that is void of lipid that can associate with lipoproteins
32
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
33
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
34
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
35
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
36
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
37
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
38
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
39
what is MTP
Microsomal triglyceride transfer protein (MTP)
40
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
41
what happens in the absense of MTP
The absence of MTP prevents VLDL synthesis and leads to apoB degradation
42
what is TGH
triacylglycerol hydrolase
43
what ist he function of TGH
* TGH hydrolyses triglycerides stored in large cytosolic lipid droplets into glycerol and three fatty acids
44
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
45
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
46
Targets currently being investigated to lower VLDL/LDL
* ApoB100 synthesis * Microsomal triglyceride transfer protein (MTP) * Phosphatidic acid phosphatase (PAP), also known as lipin-1
47