Chempath 2: Lipoprotein metabolism, CVD and obesity

Question 1

Which enzyme causes production of cholesterol ?

Answer 1

HMG CoA reductase

Question 2

Which lipoprotein is the largest ?

Answer 2

Chylomicrons

Question 3

Which lipoproteins are the smallest ?

Answer 3

HDL

Question 4

What does PCSK9 do ?

Answer 4

Down regulates LDL receptors on the liver, causing increased LDL concentration in the plasma

Question 5

role of different lipid carriers in the blood

Answer 5

chylomicrons - carry dietary cholesterol and TG
VLDL - rich in exogenously synthesised TG
LDL - carries cholesterol to peripheries
HDL - returns cholesterol to liver

Question 6

what is the main carrier of cholesterol

Answer 6

LDLs

Question 7

describe the fate of cholesterol from the diet and bile

Answer 7

NPC1L1 transports cholesterol across the intestinal epithelium - lymphatics - liver
ABC G5 and ABC G8 transport cholesterol back into the intestinal lumen
bile acids absorbed in the terminal ileum
cholesterol entering liver down regulates activity of HMG CoA reductase
amount of cholesterol synthesised in the liver is reduced

Question 8

what’s the role of HMG CoA reductase

Answer 8

produces cholesterol from mavalonic acid and acetate

Question 9

what are the 2 fates of cholesterol made/ transported to the liver

Answer 9

hydroxylation by 7 a hydroxyls into bile acids

esterification by ACAT - cholesterol ester - incorporated into VLDL particles with TG and apoB

Question 10

what is the role of the ABC A1 transporter

Answer 10

allows HDL to pick up excess cholesterol from the periphery

Question 11

what is the role of CETP

Answer 11

mediates movement of HDL - VLDL

TG from VLDL to HDL

Question 12

describe transport of triglycerides

Answer 12

VLDL = transporter in fasting state
exogenous TG transported via chylomicrons into plasma - chylomicrons hydrolysed to FFA - take up by lover and adipose tissue - liver resynthesises FFA into TG and exports into VLDL

Question 13

features of FH (type II)

Answer 13

dominant mutations of:

LDLr, ApoB, PCSK9

Question 14

features of polygenic hypercholesterolaemia

Answer 14

multiple gene mutations including NPC1L1, HMGCR and CYP7A1

Question 15

features of familial hyperalphalipoproteinaemia

Answer 15

increased HDL due to deficiency in CETP

longevity

Question 16

features of phytosterolaemia

Answer 16

increased levels of plant sterols
ABC G1 AND G8 mutations
premature atherosclerosis

Question 17

features of PCSK9 mutations

Answer 17

least common mutation resulting in FH
protein binds to LDLR and promotes its degradation
increased bd of LDLR

Question 18

features of primary triglyceridaemia

Answer 18

familial type 1 - lipoprotein lipase/ ApoC II deficiency

familial type IV - increased synthesis of TG

familia type V - ApoA V deficiency

Question 19

what is primary mixed hyperlipidamia

Answer 19

familial combined hyperlipidaemia
familial hepatic lipase deficiency 
familial dysbetalipoproteinaemia (type III)

Question 20

list some conditions that can cause secondary hyperlipidaemia

Answer 20

hormonal factors - pregnancy, hypothyroidism
metabolic disorders - diabetes, gout, storage disorders
renal dysfunction - nephrotic syndrome, CRF
obstructive liver disease
toxins - alcohol
iatrogenic - antihypertensives

Question 21

list forms of hypolipidaemia

Answer 21

A beta-lipoproteinaemia - deficiency of MTP
Hypo beta-lipoproteinaemia - low LDL - ApoB gene mutation
Tangier disease - deficiency of HDL caused by ABC A1 deficiency
Hypo alpha-lipoproteinaemia - mutation of ApoA1

Question 22

list types of statin lowering drugs

Answer 22

statins
nicotinic acid - rise in HDL
vibrates - lower TG
ezetimibe - cholesterol absorption blocker
colestyramine - resin that binds bile acids and reduces their absorption

Question 23

list novel forms of lipid-lowering drugs

Answer 23

anti - PCSK 9

MTP inhibitor

Question 24

list treatments for obesity

Answer 24

orlistat (pencreatic lipase inhibitor)
bariatric surgery…
gastric banding (reduce stomach size)
roux- en-Y bypass (anastomose distal jejunum to stomach)
biliopancreatic diversion (connect smaller stomach to terminal ileum)