Lipid Transport Flashcards
describe the properties of FFA
- formed from triglycerides stored in adipose tissue
- circulates bound to Na+ salt particularly the albumin protein
- saturation at 2mM of FA molecules
- enters cells by simple diffusion
- intracellular [FA] kept low
why do FFA need to travel bound to proteins?
if unbound they will act as detergents
what is a lipoprotein?
biochemical assembly whose purpose is to transport hydrophobic lipid molecules in water, blood, extracellular fluid
what is the structure of a lipoprotein?
- membrane consists of phospholipids and cholesterol and large apolipoproteins
- in centre, there are cholesterol esters and triacylglycerol
what are the 5 lipoproteins?
- chylomicrons
- very low density lipoproteins (VLDL)
- intermediate density lipoproteins (IDL)
- low density lipoproteins (LDL)
- high density lipoproteins (HDL)
what are the compositions of the 5 lipoproteins?
-comp varies between diff lipoproteins
- CHYLOMICRONS: most (90-95%) triglycerides, so the least dense
- VLDLs: mostly triglycerides (53%)
- LDLs: mostly (50%) cholesterol
- IDLs: intermediate in all (highest is triglycerides, 31%)
- HDLs: mostly (49%) protein
what are apoproteins/apolipoproteins?
proteins that bind lipids together to form lipoproteins
what are the functions of apoproteins?
- structure
- solubilise lipids
- act as enzymes or enzyme cofactors
- tissue targeting
what is an example of apoproteins acting as enzymes or enzyme cofactors?
- APO C2 activated lipoprotein lipase (breaks down fat in form of triglycerides)
- APO A1 activates lecithin-cholesterol acyl transferase (converts free cholesterol into cholesteryl esters)
what is an example of apoproteins involved in tissue targeting?
- APO B100 and APO E bind to the LDL receptor
- APO E binds to the HDL receptor
how does the synthesis of chylomicrons happen?
- forms in the cells that line the gut
- in lumen of gut, triglycerides broken down into FA
- FA and monoglycerides brought into mucosal cell where they are reformed into triglycerides
- they are combined with other lipids proteins to form chylomicrons
how and why are chylomicrons delivered directly into the lymph system?
- secreted into lymphatics which carries them via thoracic duct into superior vena cava
- dietary fats avoid direct delivery to liver and made available to the extra hepatic tissue
where are digested proteins and carbohydrates delivered?
released into portal vein and delivered directly into liver
how does a nascent chylomicron become a mature chylomicrons?
nascent chylomicron interacts w HDL and pick up certain apoproteins
-occurs in SER
what are chylomicrons for and how are they removed?
- important for transporting exogenous dietary lipids from gut around circulation
- they reflect meal composition
- remnants are removed by liver
what do chylomicrons contain and what is their lifeline?
- contains fat soluble vitamins like vit A and e
- lifetime in circulation is 1 hour
why doe chylomicrons have a low density?
due to high [triglyceride]
how does lipoprotein lipase work?
- LPLs bind to and activated by APO C2
- lipoprotein binds to LDL and triglycerides pithing are degraded
where are LPLs found?
vary with tissue, found in cells that use a lot of fats
what is hyperlipidaemia?
abnormally elevated levels of any/all lipids or lipoproteins in the blood
what are the different types of hyperlipiaemia?
- T1: caused by deficiency in LPL or APO C2
- T2: high LDL
- T4L: most common: increased VLDL due to obesity and alcohol abuse
what are VLDLs and what are they metabolised by?
- responsible for transporting endogenously-synthesis lipids
- metabolised by LPL as they circulate
what is VLDL halflife nad what is their formation enhanced by?
- HL: 15-60mins
- enhanced by dietary intake of carbs, circulating FFAa, alcohol, raised insulin, decreased glucagon
how does VLDL convert in mature VLDL and where is it synthesised?
- synthesised in liver, ER, GA
- when released as nascent VLDLs, they only have APO B100 apoprotein
-when they interact w HDL, HDL donates APO C2 and APO E making it mature
what are the 2 fates of VLDLs?
- when lost majority of triglyceridesm remnants return to liver or converted to IDLs
- converted to LDLs which will be removed by liver and non-hepatic tissue for steroid biosynthesis
what are the functions of LDLs?
- major carriers of cholesterol
- metabolised slowly (3 days)
- catty cholesterol to periphery and regulate denovo synthesis of cholesterol
- has APO B100 so can bind to receptor on hepatocytes
what are the 3 ways HDLs are made?
- as nascent HDLs in liver nad intestine
- budding from VLDLs and chylomicrons
- from free APO A1
how do HDLs remove cholesterol from circulation?
- contain enzyme lecithin-cholesterol acyltranferase (LCAT)
- LCAT modifies free cholesterol and retains it within HDL
- prevents cholesterol from diffusing out of HDL
how does HDL pick up cholesterol?
- reverse cholesterol transport
- occurs in plasma and endothelial cells
- they express ABCA1 transporter which moves cholesterol from extracellular surface of membrane and interacts w APO A1 on HDLs to transport cholesterol away
what is the significance of the HDL/LDL ratio and what is the normal ratio?
- HDL referred to good cholesterol dn LDL as bad
- ratio used to asses susceptibility to heart disease
-normal is 3.5
how are lipoproteins removed from circulation?
removed by receipt mediated endocytosis
describe the receptor mediated endocytosis in relation to LDLs
- LDLs bind to specific LDL receptor on endothelial cells
- cause for the invagination of LDL and receptor which forms an endoscope
- in endoscope, receptor nad LDL dissociate so receptor can be recycled
- LDL broken down by fusion of lysosome with endosome
- cholesterol esters converted to cholesterol where they are immediately esterified
- triglycerides broken down to give FA which can be further metabolised into aa
how is receptor mediate endocytosis regulated?
-regulated by intracellular [cholesterol]
-which regulates expression of new and existing receptors on membrane
-witj increased cholesterol, HMG-CoA reductase energy inhibited
-
what is an example of when there is a loss of LDL receptor function?
-familial hypercholesterolemia
- loss of LDL receptor function
- 4x the normal cholesterol serum levels
- develop blocked arteries
- tend to die young from heart attacks
- de novo synthesis not regulated by LDL
- single aa substitution prevents localisation of LDL receptor to coated pits
what are the 2 types of receptors and where are they present?
- high affinity LDL receptor
- low affinity scavenger receptor
- present on endothelial cells, macrophages, vascular smooth muscle cells
- low affinity scavenger receptors activated when plasma LDL levels high or when chemically modified
what are 3 situations where there are abnormalities in lipid transport?
- diabetes mellitus: increased [FA] mobilisation, decreased [LDL]
- obesity: can cause hypertension, hyperglycaemia, hypoglycaemia
- gene defects of proteins: leads to hypercholesterilemia, atherosclerosis
where do chylomicrons transport fat?
small intestine to capillaries
where do IDL and LDL transport fat?
capillaries to extra hepatic tissue
where does HDL transport fat?
extra hepatic tissue to liver
