Lecture 6: Lipids, Metabolism, Disorders and Analysis Flashcards
(37 cards)
What are lipid fractions?
- Cholesterol
- Fatty acids
- Triglycerides
- Phospholipids
- Other lipid soluble substances (fat-soluble vitamins and steroid hormones, etc. (much smaller amount)
What is cholesterol?
A vital lipid in the body used for making cell membranes, tissues, steroid hormones, bile acid, vitamin D. Can be made exogenously or endogenously.
Where and how is cholesterol made?
Made in the liver from acetyl-CoA.
The reaction HMG-CoA synthase (3-hydroxy-3-methylglutaryl-CoA synthase) produces HMG-CoA from acetyl-CoA, before HMG-CoA is converted into mevalonic acid by HMG-CoA reductase, which goes on to become cholesterol.
How is cholesterol transported?
Transported as lipoproteins:
-LDL
-HDL
-IDL
What function does cholesterol play in membranes?
It is present in cell membranes to maintain the fluidity, compressibility, water penetration, and intrinsic curvature.
What are triglycerides?
Fats in the body that are stored forms of fatty acids, present in many cells in the body but especially in adipose. Held together by a glycerol molecule with 3 ester bonds holding 3 fatty acid chains.
Triglycerides that contain both saturated and unsaturated fatty acids are vital for cell membranes.
Triglycerides are transported as lipoproteins (VLDL and chylomicrons).
Free fatty acids are transported in plasma bound to albumin.
What are fatty acids?
Long carbohydrate chains with a carboxylic acid group on one end.
Can have C=C bonds in the chain (unsaturated), or only C-C bonds (saturated). Can be short, medium, or long chain.
Where are certain types of fatty acids obtained from in the diet?
Saturated - Animal sources
Unsaturated - Plant sources
An exception is omega-3 fatty acids from fish
What are phospholipids?
Similar to triglycerides, with a glycerol molecules bonded to 2 fatty acid chains with the final bond being to a phosphate group bonded to a choline molecule.
What are lipoproteins?
Lipids are not soluble, and therefore must be transported by something in plasma. Free fatty acids bind to albumin. And other lipids circulate as lipoproteins.
The structure consists of a single phospholipid layer (with some cholesterol) emulsifying a collection of triglycerides and cholesterol esters, Apolipoproteins are present in phospholipid layer. This creates a polar shell and non-polar core.
What types of lipoproteins are there?
Chylomicrons
VLDL -Very low density lipoprotein
IDL -Intermediate density lipoprotein
LDL -Low density lipoproteins
HDL -High density lipoproteins
From order of least dense to most.
What are chylomicrons?
- The largest and most buoyant lipoprotein.
- Formed in the intestine and are a transport vehicle for dietary fat.
- Triglyceride rich
- Exogenous pathway
What are VLDLs?
- Second largest lipoprotein
- Largest lipoprotein that contains endogenous lipid
- Triglycerides are endogenous
- Triglyceride rich
What are IDLs?
- Intermediate composition of lipids
- Carries endogenous lipids
- Produced as an intermediate between VLDL and LDL
- Core contains cholesterol ester and triglycerides.
What are LDLs?
- The main cholesterol containing lipoprotein
- End product of VLDL catabolism
- Mostly cholesterol esters in core
- Has apolipoprotein B100 embedded in phospholipid monolayer, as well as embedding itself in the core.
- “bad cholesterol”
- Endogenous pathway
What are HDLs?
- Smallest and densest lipoprotein
- Crucial component of endogenous and exogenous pathways
- “good cholesterol”
- Cholesterol rich
What are apolipoproteins?
An important part of structure and metabolism of lipoproteins
- Four classes: A, B, C, and E (former D was placed in class A
- Serves as a ligand for receptors and an enzyme cofactor
What apolipoproteins are present on which lipoproteins?
A1 and A2 - Chylomicrons, HDL
B48 - Chylomicrons. VLDL
B100 - IDL, VLDL, LDL
C2 - Chylomicrons, HDL, VLDL, IDL
C3 - Chylomicrons, HDL, VLDL, IDL
E - C3 - Chylomicrons, HDL, VLDL, IDL
What does each apolipoprotein do?
A1 and A2 - LCAT activator
B48 - Secretion of chylomicrons/VLDL
B100 - LDL receptor binding
C2 - Lipoprotein lipase activator
C3 - Lipoprotein lipase inhibitor
E - IDL and remnant particle receptor binding
What is lipoprotein (a)?
- Strong risk factor for CVD
- Pro-inflammatory, pro-atherotic, pro-thrombotic
- LDL-like particle containing apoB bound to apo(a)
- Not lowered by statins / ezetimibe / fibrates
- Plasma conc. is genetically determined, and short apo(a) means high conc. in blood
- Some new drugs can target it
What is lipoprotein X?
Found only in plasma of subject in cholestasis or have familial LCAT deficiency (cholesterol esterification enzyme).
Major protein is albumin, with Apo C and D also.
Contains no ApoB, not recognised by LDL-Receptor
Can slow down the process of atherosclerosis by inhibition of LDL oxidation.
What is lipoprotein lipase?
Attached to luminal surface of endothelial capillaries.
Predominant on adipose and muscle cells.
Catalyses triglycerides into constituents
What is LCAT?
Enzyme for cholesterol -> cholesterol ester
What is CEPT?
Protein that transfers cholesterol esters from HDL to VLDL
