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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
Q

what are y-migrating lipoproteins

A

apoE-only HDL

26
Q

what lipoproteins are found between the origin and b-migrating

A

LpX and
Lp(a)

27
Q

what is another class of lipoproteins

A

lipoprotein (a) Lp(a)

28
Q

lipoproteins obtained by affinity
chromatography for apoB would be named

A

LpB

lipoproteins separated by protein content

affinity chromatography for apolipoproteins

29
Q

what are some physical properties of lipoproteins

A
  • Density is directly proportional with
    percent protein content and percent
    phospholipid content
  • Density is inversely proportional with
    triglyceride content
30
Q

what are some protperties of HDL subclasses of lipoproteins

A
  • Density is directly proportional with
    percent protein content
  • Density is inversely proportional with size,
    PL content, CE content, TG content, and
    FC content
31
Q

apolipoprotein

A

apo): a protein that is
void of lipid that can associate with
lipoproteins

32
Q

how many and roughly what are the types of lipoproteins

A
  • 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
Q

non exchagneable versus exchangeable apolipoproteins

A
  • ApoB48 & apoB100 NEVER fall off a
    lipoprotein; they are non-exchangeable
  • All other apo’s can fall off a lipoprotein;
    they are exchangeable
34
Q

synthesis of VLDL

A

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
Q

ApoB-100 vs. apoB-48

A
  • 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
Q

apoBs

A

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
Q

what differs apob48 from apob100 and vice versa

A

Only one apoB-48 is present on a
chylomicron, and only one apoB-100 is
present on VLDL, IDL, or LD

38
Q

explain the apoB cotranslational/cotransolational synth

A
  • 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
Q

what is MTP

A

Microsomal triglyceride transfer
protein (MTP)

40
Q

what is the function of MTP

A
  • 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
Q

what happens in the absense of MTP

A

The absence of MTP prevents VLDL
synthesis and leads to apoB degradation

42
Q

what is TGH

A

triacylglycerol hydrolase

43
Q

what ist he function of TGH

A
  • TGH hydrolyses triglycerides stored in
    large cytosolic lipid droplets into glycerol
    and three fatty acids
44
Q

what happens to the TGH hydrolyisis products

A
  • The hydrolysis products are liberated from the lipid droplets into the cytosol, where they are used toward re-synthesizing triglycerides
45
Q

what is the fate of the newly synth TG

A
  • 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
Q

Targets currently being
investigated to lower VLDL/LDL

A
  • ApoB100 synthesis
  • Microsomal triglyceride transfer protein
    (MTP)
  • Phosphatidic acid phosphatase (PAP),
    also known as lipin-1
47
Q
A

lipids (13 decks)

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