Chempath 2: Lipoprotein metabolism, CVD and obesity Flashcards
Which enzyme causes production of cholesterol ?
HMG CoA reductase
Which lipoprotein is the largest ?
Chylomicrons
Which lipoproteins are the smallest ?
HDL
What does PCSK9 do ?
Down regulates LDL receptors on the liver, causing increased LDL concentration in the plasma
role of different lipid carriers in the blood
chylomicrons - carry dietary cholesterol and TG
VLDL - rich in exogenously synthesised TG
LDL - carries cholesterol to peripheries
HDL - returns cholesterol to liver
what is the main carrier of cholesterol
LDLs
describe the fate of cholesterol from the diet and bile
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
what’s the role of HMG CoA reductase
produces cholesterol from mavalonic acid and acetate
what are the 2 fates of cholesterol made/ transported to the liver
hydroxylation by 7 a hydroxyls into bile acids
esterification by ACAT - cholesterol ester - incorporated into VLDL particles with TG and apoB
what is the role of the ABC A1 transporter
allows HDL to pick up excess cholesterol from the periphery
what is the role of CETP
mediates movement of HDL - VLDL
TG from VLDL to HDL
describe transport of triglycerides
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
features of FH (type II)
dominant mutations of:
LDLr, ApoB, PCSK9
features of polygenic hypercholesterolaemia
multiple gene mutations including NPC1L1, HMGCR and CYP7A1
features of familial hyperalphalipoproteinaemia
increased HDL due to deficiency in CETP
longevity
features of phytosterolaemia
increased levels of plant sterols
ABC G1 AND G8 mutations
premature atherosclerosis
features of PCSK9 mutations
least common mutation resulting in FH
protein binds to LDLR and promotes its degradation
increased bd of LDLR
features of primary triglyceridaemia
familial type 1 - lipoprotein lipase/ ApoC II deficiency
familial type IV - increased synthesis of TG
familia type V - ApoA V deficiency
what is primary mixed hyperlipidamia
familial combined hyperlipidaemia familial hepatic lipase deficiency familial dysbetalipoproteinaemia (type III)
list some conditions that can cause secondary hyperlipidaemia
hormonal factors - pregnancy, hypothyroidism
metabolic disorders - diabetes, gout, storage disorders
renal dysfunction - nephrotic syndrome, CRF
obstructive liver disease
toxins - alcohol
iatrogenic - antihypertensives
list forms of hypolipidaemia
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
list types of statin lowering drugs
statins
nicotinic acid - rise in HDL
vibrates - lower TG
ezetimibe - cholesterol absorption blocker
colestyramine - resin that binds bile acids and reduces their absorption
list novel forms of lipid-lowering drugs
anti - PCSK 9
MTP inhibitor
list treatments for obesity
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)
