Lipids and cholesterol

Question 1

What are the clinical manifestations of familial Hypercholesterolemia?

Answer 1

• Family History of high cholesterol
• high cholesterol levels due to high LDL levels
• atherosclerosis - build of of LDL plaque on the arterial walls
• High troponin - due to the rupturing of plaque buildups damaging cardiac tissue
• mutations of LDLR, PCSK9, or APOB genes
• xanthomas - yellow bumps of cholesterol under skin
• corneal arcus - grey ring around cornea

Question 2

Name the three major plasma lipids (found in the blood)

Answer 2

cholesterol, triglycerides, phospholipids

Question 3

What is cholesterol a precursor to?

Answer 3

bile salts, steroid hormones and vitamin D

Question 4

How does the brain get cholesterol?

Answer 4

de novo (newly) made synthesis from acetate because LDLs are blocked by the brain barrier

Question 5

what is the purpose of cholesterol?

Answer 5

maintain fluidity in the membrane
production of steroid hormones
production of bile salts

Question 6

what are the three key genes that are screened for if you have a family history of high cholesterol?

Answer 6

LDLR (low density lipoprotein receptor) – LDL binds and triggers a degradation pathway
APOB - ligand in LDL that binds to LDLR - 2 isoforms (48 and 100)
PCSK9 - codes for protein that removes LDL - found on hepatocytes

Question 7

describe the mechanism for LDL degradation

Answer 7

LDL binds to LDL receptors
internalisation via endocytosis
A clathrin-coated vesicle forms
clathrin coat sheds
vesicle fuses w/ an endosome
this fuses w/ a lysosome containing digestive enzymes
LDL is broken down into free cholesterol and amino acids

Question 8

what is atherosclerosis and when does it occur?

Answer 8

build up of LDL on and in arterial walls, forming plaque that blocks blood flow to the heart. this can rupture, damaging tissue and forming clots. = high troponin levels
thickens arterial walls
Increased risk of myocardinal infarction

Caused by endothelial damage via hypertension, smoking residue or genetic mutations causing high LDL in blood

Question 9

what are the two isoforms of ApoB and what is the difference between them?

Answer 9

ApoB-48 = synthesised in small intestine. Forms chylomicrons from dietary fats – associates with triglycerides for transport into tissues

ApoB100 = component of VLDL and LDL which are synthesised in the liver. – facilitates binding to LDL receptors

Question 10

What is the only apoprotein on LDL?

Answer 10

ApoB100

Question 11

Two ways body breaks down cholesterol

Answer 11

1. metabolize to bile acid (95%)
2. convert to steroid hormone (5%)

Question 12

what is Xanothomas and what causes it?

Answer 12

build up of yellow lumps of cholesterol under skin
caused by hypercholesterolemia

Question 13

Steps of LDL receptor pathway

Answer 13

1. LDL binds
2. Internalize
3. lysosomal hydrolysis
4. regulatory actions

Question 14

Where to find HMG-CoA reductase

Answer 14

on the membrane of the endoplasmic reticulum

Question 15

function of HMG-CoA reductase

Question 16

First step of cholesterol synthesis

Answer 16

HMG CoA –> mevalonate

Question 17

what are SREBP-1 and SREBP-2?

Answer 17

transcription factors that enhance gene transcription of all genes
in the cholesterol synthesis pathway AND LDL receptor genes

So increases cholesterol synthesis and uptake

Question 18

Statins affect on HMG CoA reductase?

Answer 18

Statins INHIBIT HMG CoA reductase - rate limiting step
– reducing cholesterol synthesis.

Question 19

what form do fatty acids and cholesterol take when being transported by lipoproteins?

Answer 19

as fatty acid esters and triglycerides

Question 20

which lipoprotein carries the most cholesterol?

Answer 20

LDL