Chem Path: Brief lipid update Flashcards
What is the cholesterol distribution in fasting plasma
13% VLDL
70% LDL
17% HDL
What are mixed micelles?
They are the major component of bile acids
Which enzyme facilitates transport of mixed micelles from the small intestine to the lymphatics/liver?
NPC1L1
Which enzymes facilitate movement of cholesterol from lymphatics back to the small intestine
ABC G5 and G8
What does cholesterol downregulate in the liver
HMG CoA reductase
Where do bile acids get absorbed
Terminal ileum
What are the 2 fates of cholesterol in the liver?
They can get hydroxylased into bile acids
They get turned into esters by ACAT
What happens to cholesterol esters in the liver
Get attached to VLDL by MTP and apoB TG
What is the difference between HDL and LDL
HDL brings cholesterol from peripheral cells to the liver, while LDL does the opposite
How does HDL collect cholesterol from the cells
Via ABC A1
What happens to VLDL
It is the precursor to LDL
It also get converted to HDL vis CETP and cholesterol esters and HDL gets turned into VLDL via CETP and triglycerides
What is the triglyceride distribution in fasting plasma
55% VLDL
29% LDL
11% HDL
Transient increase in chylomicrons after eating
How are triglycerides processed and transported in the capillaries
Fatty foods are broken down into FAs, which are further broken down into triglycerides, which are transported as chylomicrons
Chylomicrons are then broken down into FFAs by lipoprotein lipase
FFAs are taken up by liver and adipose tissue
Liver resynthesises FFA into triglycerides and exports them as VLDL
VLDL will also be broken down into FFAs by lipoprotein lipase
What are the 4 types of primary hypercholesterolaemia and what gene mutations are they usually associated with
Familial - LDLR, ApoB or PCSK9 - autosomal recessive
Polygenic - NPC1L1, HMG Co reductase
Familial hyper A lipoproteinaemia - Increase in HDL, CETP defic
Phytosterolaemia - ABC G5 and G8, - absorb plant sterols freely so increased risk of atherosclerosis
For FH, is hetero or homo more common?
Heterozygous
What are some signs of heterozygous FH
Corneal arcus
Xantholasma
Tendon xanthoma
What happens in PCSK 9 mutation?
PCSK 9. degrades LDLR. Mutations can either increase rate of degradation of LDLR to reduce rate of degradation
What are the 3 types of hypertriglyceridaemia
1 - Lipoprotein lipase or ApoC 2 def
4 - increased triglyceride production
5 - ApoA 5 def
What would you be able to see in type 1 hyperlipidaemia
Eruptive xanthoma
How can you differentiate between types 1 4 and 5 hyperlipidaemias?
Fridge test - chylomicrons at the top for types 1 and 5, VLDL a the top for type 4
There is a clearance problem in which type of hyperlipidaemia?
Type 1
What are the 3 types of primary mixed hyperlipidaemia
Familial combined hyperlipidaemia - some have high cholesterol some have high triglycerides
Familial hepatic lipase deficiency
Familial dys beta lipoproteinaemia
what is Familial dys beta lipoproteinaemia ApeE 4/4 associated with
Alzheimer’s
What is the classical sign of Familial dys beta lipoproteinaemia
Yellow palmar crease and eruptive xanthomas
When would you get secondary hyperlipidaemia
Nephrotic syndrome, pregnancy,
What other reasons can cause high triglycerides
Exogenous sex hormones diabetes gout obesity progressive partial lipodystrophy chronic renal failure alcohol
What other reasons can cause high cholesterol
Nephrotic syndrome
Obstructive liver disease
What are the 4 types of hypolipidaemia
AB lipoproteinaemia - Autosomal recessive - MTP deficiency - Very low LDL and VLDL
HypoB lipoprotienaemia - Autosomal dominant - ApoB
Tangier disease. - HDL deficiency - ABC A1 mutation
Hypo alpha lipoproteinaemia - ApoA1 mutation
What do statins do
Lower LDL greatly
Mild increase in HDL
Mild decrease in TG
How does nicotinic acid work
Decrease in LDL
Great increase in HDL
How do fibrates work
Decrease TG
What does exetimibe do?
Reduces LDL
What are 3 medications in the pipeline now
MTP inhibitor
Anti PCSK9 - reduces LDL
Anti sense apoB oligonucleotide - reduces LDL
What is orlistat
Prevents fat abosrption
What are the 3 surgical interventions for obesity
Gastric banding
Roux en Y gastric bypass
Biliopancreatic diversion
