Lipid Transport Flashcards
Describe free fatty acids.
- they’re formed from triacylglycerides stored in adipose tissue
- it circulates bound to protein as a Na+ salt, particularly the albumin protein
- saturation occurs at about 2 mM of fatty acid molecules
- it enters the cell by simple diffusion
- the intracellular concentration of free fatty acids is kept low
Why do free fatty acids (FFAs) need to travel bound to a protein?
If unbound, they will act as a detergent.
What is a lipoprotein?
It is a biochemical assembly whose purpose is to transport hydrophobic lipid molecules in water, as in blood or extracellular fluid.
Describe the structure of a lipoprotein.
The membrane consists of phospholipids and cholesterol, and large apolipoproteins.
In the centre, there are cholesterol esters and triacylglycerol.
What are the five lipoproteins?
- Chylomicrons
- Very Low-Density Lipoproteins (VLDLs)
- Low-Density Lipoproteins (LDLs)
- Intermediate Density Lipoproteins (IDLs)
- High-Density Lipoproteins (HDLs)
Describe the different lipoprotein compositions.
- CHYLOMICRONS: has the 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?
They are proteins that bind lipids together to form lipoproteins.
What are the functions of apoproteins?
- structural functions (the backbone of the lipoproteins)
- to solubilise lipids (lipoproteins allow lipids to travel in aqueous solution)
- act as enzymes or enzyme cofactors
- tissue targeting
Give examples of apoproteins acting as enzymes/enzyme cofactors.
- APO C2 activates LipoProtein Lipase (LPL, breaks down fat in the form of triglycerides, so a lipoprotein expressing this apoprotein will lose its triglycerides)
- APO A1 activates Lecithin-Cholesterol AcylTransferase (LCAT, converts free cholesterol into cholesteryl esters)
Give examples of apoproteins involved in tissue targeting.
- APO B100 and APO E bind to the LDL receptor
- APO E binds to the HDL receptor
List the apoproteins involved in the composition of the different lipoproteins.
- CHYLOMICRONS: B48, APO C2, C3 and E
- VLDL: B100, APO C1, C2, C3 and E
- LDL: B100
- IDL: B100, APO E
- HDL: APO A1, A2, C1, C3, D and E
Describe the synthesis of chylomicrons.
They’re formed in the cells that line the gut.
In the lumen of the gut, triglycerides are broken down to fatty acids. Those, along with monoacylglycerols are brought into the mucosal cell and reformed into triacylglycerides.
Those then combine with other lipids and proteins in the cell to form chylomicrons.
Why are chylomicrons delivered directly to the lymph system?
Chylomicrons are secreted into the lymphatics which carries them via the thoracic duct to the superior vena cava. By this pathway, dietary fats avoid the direct delivery to the liver and instead are made available to the extrahepatic tissue.
In contrast, digested proteins and carbohydrates are released into the portal vein and delivered directly to the liver.
Describe the conversion of a nascent chylomicron to a mature chylomicron, in terms of apoproteins.
When first formed, the only apoprotein chylomicrons consist of are the ApoB48.
As it circulates, it interacts with HDL and the HDL donates certain apoproteins to the nascent chylomicron, primarily Apo C2 and Apo E. This forms a mature chylomicron.
This donation occurs in the SER.
Describe chylomicrons.
- they’re solely important for transporting exogenous (dietary) lipids from gut around the circulation
- they reflect meal composition (if a fatty meal is ingested, there will be many chylomicrons of that composition)
- they have a low density due to a high number of triglycerides
- they contain fat soluble vitamins such as Vitamins A and E
- their lifetime in the circulation is about one hour (the triglyceride’s is about 5 minutes)
- their remnants are removed by the liver, with the help of Apo E
Describe Lipoprotein Lipase (LPL) and how it works.
LPLs bind to and are activated by Apo C2.
A lipoprotein binds to the LDL, and the triglycerides in it are broken down into monoacylglycerols and fatty acids.
Lipoprotein Lipases levels vary with the tissue, so you will see them in cells that utilise a lot of fats. There are different isoforms of the enzyme expressed in the different tissue. Examples of such tissue would be mammary, muscle or adipose tissue.
The Km of the LPL isoform in adipocytes is greater than in muscle.
What is Hyperlipidaemia?
Hyperlipidaemia is abnormally elevated levels of any or all lipids/lipoproteins in the blood.
What are the different types of hyperlipidaemia?
- TYPE 1: This can be caused by either a deficiency in lipoprotein lipase or Apo C2 – characterised by high plasma triglyceride
- TYPE 2: Characterised by high LDL – most caused by a genetic defect in the synthesis processing or function of the LDL receptor
- TYPE 4: Most common results in increased VLDL concentrations often due to obesity or alcohol abuse
Describe VLDLs.
- they’re responsible for transporting endogenously-synthesised (synthesised in the liver) lipids
- they’re metabolised by LPL as they circulate - TG half-life is 15-60 minutes
- their formation is enhanced by: dietary carbohydrates, circulating FFAs, alcohol, raised insulin and decreased glucagon
Describe the conversion of a nascent VLDL to a mature VLDL , in terms of apoproteins.
VLDLs are synthesised in the liver, ER and Golgi.
When released as nascent VLDLs, they only have the Apo B100 apoprotein. When they interact with HDL, the HDL donates Apo C2 and Apo E to the VLDL, making it mature.
What is the difference between Apo B100 and Apo B48?
They are both synthesised from the same gene. The only difference is that B100 is 100% of the gene, while B48 is 48% of that gene.
Their expression is differentially regulated within the cell types.
What are the two fates of VLDLs?
1) When it’s lost the majority of its triglycerides, its remnants will return to the liver (removed by Apo E).
2) It may form IDLs (via Lipase), and those IDLs may be removed by the liver or may be converted to LDLs, which will be removed by the liver and by non-hepatic tissue for steroid biosynthesis.
Describe LDLs.
- they’re the major carrier of cholesterol
- they’re metabolised slowly - 3 days
- they carry cholesterol to the periphery and regulate de novo synthesis
- they contain one Apo B100, which can bind to a specific receptor on hepatocytes
What are the three ways in which HDLs are made?
- primarily, in the liver and intestines
- by budding from VLDL and chylomicrons
- from the free Apo A1
