Lipid Transport Flashcards
(52 cards)
Where are lipids transported from?
- gut to liver
- liver to non-hepatic tissue including adipocytes
- non-hepatic tissue back to liver
Fats + lipids in circulation?
Triacylglycerols (45%) Cholesterol esters Cholesterol (15%) Phospholipids (35%) Free FA (5%) % in plasma varies with nutritional state All are insoluble in water
How polyunsaturated FA are ligands for transcription factors involved in energy metabolism?
Role in regulation of insulin metabolism :
increase lipid oxidation in liver + muscle
decrease genes involved in lipogenesis in liver + adipose tissue
-Increase expression of UCP-2 + 3 in mitochondria to increase thermogenesis
Features of FFA?
- Formed from triacylglycerides stored in adipose tissue
- Circulates bound to protein as Na+ particularly albumin as unbound FA acts as a detergent
- Saturation occurs at about 2mM FA molecules
- FA enter cells by simple diffusion
- Intracellular concentration FFA kept low
Features of lipoprotein?
-Carried in blood as plasma lipoproteins
-5 types of lipoprotein :
chylomicrons
very low density lipoproteins (VLDL)
intermediate density lipoprotein (IDL)
low density lipoproteins (LDL)
high density lipoproteins (HDL)
-Each particle has diff function
Functions of apolipoproteins / apoproteins?
-Structural = form substrate in which lipid can be constructed
-Solubilise lipids = so body transports a difficult class of
molecules
-Act as enzymes or enzyme cofactors (co-enzymes) :
Apo C2 activates lipoprotein lipase
ApoA1 for lecithin:cholesterol acyltransferase
-Tissue targeting :
Apo B100 + Apo E binds LDL receptor
Apo E binds HDL receptor
Lipoprotein composition?
Chylomicrons : B48, Apo C2, C3, E VLDL : B100 Apo C1, C2, C3, E (VLDL made in liver released with only B100 when circulates it gets Apo C + E from HDL) IDL : B100, Apo E LDL : B100 HDL : Apo A1, A2, C1, C3, D, E
Describe how dietary lipids travel?
- in gut triglycerides -> FA + monoacylglycerols via lipases
- pass from gut lumen into gut epithelial cells
- converted back into triglycerides
- triglycerides assembled into chylomicron with other lipids (phospholipids, cholesterol) + proteins.
- chylomicrons released into lymphatics
- carried via thoracic duct to SVC
- so dietary fats avoid direct delivery to liver + made available to extrahepatic tissue (diff to digested proteins, carbs which released into portal vein, delivered directly to liver
Features of dietary lipids?
- Low density due to high TG
- Apo C2, C3, E, B48 added in SER
- Secreted by reverse pinocytosis in to lymphatics
Features of chylomicron?
- Content reflects meal composition
- Low density due to TAG
- Contain fat-soluble vitamins A + E
Describe circulation of chylomicron
-circulate for 1hr but half-life of TAG only 5min
-so modified by lipoprotein lipases in circulation
-breaksdown TAG –> uptake of FA by tissues
-in circulation density increases as TAG removed - chylomicron remnants
-removed by liver by interaction of Apo E with
receptors on hepatocytes
Role of vit E?
antioxidant preventing oxidation of lipids which are associated with heart disease
Describe how lipoprotein lipase (LPL) works
- expressed on top of endothelial cells
- binds to + activated by Apo C2 on lipoprotein
- TG broken down + diffusion across membrane of FFA across membrane
- continues as chylomicron circulates
- gains density
What’s LPL on adipocytes stimulated by?
insulin
Diff types of hyperlipidaemia?
- Type 1: Def in lipoprotein lipase or Apo C2 + characterised by high plasma triglyceride
- Type 2: Genetic defect in synthesis, processing or function of LDL receptor + characterised by high LDL
- Type 4: Most common form –> raised VLDL conc due to obesity or alcohol abuse
Role of VLDL
transport lipids derived from liver around body
Role of chylomicrons?
transporting exogenous lipids from gut around circulation
What are VLDLs?
-synthesised in liver ER + golgi
-released with B100 + acquire Apo E, C2 from HDL
-interact with endothelial layer + metabolised by LPL
-remnant removed by liver by apoE (TG half life 15-60 min) :
60% VLDL remnants removed by liver
40% removed by adrenal + gonadal tissue (cholesterol used for hormone production) using B100 to bind to LDL
If excess LDL, receptors saturated + excess removed via low affinity scavenger receptor
What are VLDLs formation enhanced by?
- Excess dietary carb
- Circulating FFA
- Alcohol enhances VLDL synthesis so increases lipid transport
- Insulin + decreased glucagon
Describe process of VLDL
-VLDL released as nascent particle
-acquires ApoE + ApoC-2 from HDLs
-form mature VLDLs
-circulate + acted upon by LPL
-FA enters tissues + get smaller
-2 pathways :
~return to liver as VLDL remnants – removed by ApoE (50%)
~converted into IDLs via removal of more TGs
in liver sinusoids IDLs -> LDLs
LDLs taken up by liver + removed or taken up by non-hepatic tissue via interacting with LDL receptor
Role of LDL?
carrier of cholesterol
What are LDLs?
- Metabolised slowly 3 days
- Carry cholesterol to periphery + regulate de novo synthesis of cholesterol via B100 binding to specific receptor on hepatocyte
Role of HDL?
reverse cholesterol transport
- take up circulating cholesterol from VLDLs, dead, dying cells
- take cholesterol back to liver + steroid producing cells
How are HDLs made?
in liver + intestine by budding from VLDL + chylomicrons
from free ApoA1
