Artherosclerosis And Familial Hypercholesterolaemia

Front 1

4 trafficking pathways

Back 1

default, regulated, targetting to lysosome and import

Front 2

default pathway?

Back 2

export to the surface - no specific signal

Front 3

regulated pathway?

Back 3

export to storage vesicle - no specific target signal

Front 4

targetting to lysosome?

Back 4

requires a specific signal

Front 5

import pathway?

Back 5

from surface (endocytosis) and may require a specific signal.

Front 6

vesicular transport

Back 6

proteins are transported between organelles in vesicles, there are different types of vesicles with different destinations, they move along microtubules and their docking and fusion is receptor mediated.

Front 7

steps in vesicle traficking are?

Back 7

budding, uncoating, docking and fusion and cargo release.

Front 8

types of endocytosis?

Back 8

phagocytosis, pinocytosis and receptor-mediated endocytosis.

Front 9

clathrin coated vesicles

Back 9

occur at specialised regions of the plasma membrane called clathrin coated pits. membrane curvature is induced during polymerisation as the clathrin forms a 3d spherical lattice. coated vesicle buds from plasma membrane taking lipids and proteins with it.

Front 10

Early endosome is the

Back 10

sorting area = post office.

Front 11

from early endosome, vesicles can move to

Back 11

the cell surface for recycling, the opposite surface in polarized cells (trancytosis) or the lysozomes via late endosomes.

Front 12

proteins that are directed into clathrin-coated transport vehicles via recptors undergo what type of endocytosis?

Back 12

receptor-mediated

Front 13

what does receptor-mediated endocytosis serve to do?

Back 13

concentrate the protein at sites of plasma membrane internalisation

Front 14

what happens to the receptor once after the release of cargo in RME occurs?

Back 14

it is recycled back to the plasma membrane.

Front 15

cargo and receptor dissociate in RME due to a change in?

Back 15

pH

Front 16

internalizing receptors carry a signal in the cytoplasmic domain. signal promoters bind to ------- which associate with clathrin.

Back 16

adaptins

Front 17

Cholesterol is a key component of membranes and precursor of steroid hormones and bile acids. in which ways can it be obtained?

Back 17

synthesized and obtained from the diet.

Front 18

cholesterol is insoluble and so how does it travel in the blood?

Back 18

via lipoproteins

Front 19

what are lipoproteins?

Back 19

particles containing phospholipid, fatty acids, cholesterol and apoproteins. they are classified according to their desity.

Front 20

what are the various classifications of lipoproteins?

Back 20

LDL, IDL, HDL and VLDL

Front 21

cholesterol, fatty acids and apoprotein are assembled into what?

Back 21

VLDL

Front 22

Lipoprotein lipase removes fatty acids, reducing/increasing particle density?

Back 22

reducing to IDL

Front 23

IDL is then further degraded to a particle rich in cholesterol containing a single protein type (?)

Back 23

apoB in LDL

Front 24

LDL is used by?

Back 24

adrenals, gonads, adipose tissue and the liver.

Front 25

LDL receptors must be present where for LDL to be taken in by clathrin mediated pathway?

Back 25

the cell surface

Front 26

the LDL receptor binds?

Back 26

apoB in LDL and apoE in VLDL

Front 27

where is the LDL receptor mainly expressed?

Back 27

the liver, fat and adrenal cells. 45% of LDL is removed/day

Front 28

gene regulation of LDLR is up/down regulated when cholesterol levels are low?

Back 28

up

Front 29

FH - familial hypercholesterolaemia is an inherited disease in which patients have ELEVATED plasma cholesterol levels. Homozygotes develop?

Back 29

Heart disease (artherosclerosis) and die in their teens.

Front 30

A high risk of heart attack before 40 and pertaining to 5% of all HA victims under the age of 60 is what underlying disorder?

Back 30

FH heterzygosity.

Front 31

In FH, where is cholesterol deposited?

Back 31

in the skin and in the tendons

Front 32

FH is an autosomal dominant disease effecting mainly..

Back 32

the LDL receptor but can have minor effects on its ligand, apoB

Front 33

Fatty deposits build up on blood vessel walls, constrict flow and may eventually cause complete blockage of the vessel. Characteristics of:

Back 33

Artherosclerosis.

Front 34

Artherosclerosis is initiated by

Back 34

injury to the blood vessel during which LDL is attracted as part of the healing process.

Front 35

Sequestered LDL triggers the inflammatory response by:

Back 35

becoming oxidised, damaging surrouding cells and attracting monocytes.

Front 36

Macrophages called to the site of inflammation take up the oxidised LDL and accumulate cholesterol esters becoming..

Back 36

foam cells

Front 37

dead and dying foam cells form the

Back 37

fatty strak and contribute to the blockage

Front 38

excess plasma LDL in FH patients ______ this process

Back 38

accelerates. it usually happens in people without FH, yet it takes a very long time.

Front 39

the major and minor causes of FH is

Back 39

mutation of the LDL receptor gene and apoB protein gene respectively

Front 40

how many LDL receptor mutants are there?

Back 40

six

Front 41

Class I is characterised by

Back 41

no synthesis of the receptor protein

Front 42

Class II is characterised by

Back 42

aggregation and degradation of the receptor due to misfolded protein in domain 1 or 2.

Front 43

Class III is characterised by

Back 43

mutation in domain one which results in failure of LDL binding.

Front 44

Class IV is characterised by:

Back 44

mutations that cause failure of the receptor to internalise.
1. truncation - missing cytoplasmic domain and trasmembrane region, secreted
2. receptor lacks cytoplasmic sequences and internalization signal
3. point mutation destroying the internalisation signal

Front 45

Class V is characterised by:

Back 45

degradation of both receptor and cargo because of unassociation of ligand and receptor in the early endosome. Receptor does not recycle and the level of receptors on the surface lowers.

Front 46

Class VI is characterised by:

Back 46

domain 5 mutation leading to misdirected expression. it is expressed on the apical surface as opposed to on the basolateral surface to interact with the blood stream.

Front 47

FH treatment includes

Back 47

dietary modification (low chol foods), drugs that lower blood cholesterol levels, apheresis - remove LDL from blood and liver transplant.
The future holds gene therapy.

Front 48

Apheresis is similar to

Back 48

dialysis, cholesterol is phisically removed from the blood chromatographically.

Front 49

Stantins prevent cholesterol synthesis by inhibiting

Back 49

HMG CoA reductase

Front 50

Bile acid sequesterants increase the amount of cholesterol diverted to

Back 50

bile acid synthesis

Front 51

FH gene therapy

Back 51

piece of liver had normal LDL gene introduced, liver was then reintroduced into the patient taking into account regenerative propertion and the LDL/HDL ratio decreased!