Week 5 Flashcards
What are the functional roles of apoproteins?
Recognition of cell surface receptors or activation of enzymes
Describe how the structure of a lipoprotein enables it to perform its function.
Hydrophobic regions that interact with lipids and hydrophilic regions that interact with water.
What are the two remnant classes of lipoproteins and what are they remnants of?
Chylomicron remnants - removal of TAGs from chylomicrons
IDLs - removal of lipids from VLDLs
What is the function of chylomicrons?
Transport of dietary lipids from gut to the tissues such as adipose tissue
What is the function of LDLs?
Transport of cholesterol from the liver to the tissues
What is the function of HDLs?
Transport of cholesterol from tissues to the liver for disposal as bile salts
What is the function of VLDLs?
Transport of TAGs from liver to adipose tissue for storage
Describe how fatty acids from the diet are transported to the tissues.
TAGs hydrolysed by pancreatic lipase, fatty acids absorbed into epithelial cells of the small intestine.
Reesterified to triacylglycerols with glycerol phosphate from glucose metabolism.
Packaged into chylomicrons with other dietary lipids (cholesterol, fat soluble vitamins). Transported to tissues via lymphatic system then blood stream.
Tissues have extracellular enzyme lipoprotein lipase - hydrolyse TAGs, take up fatty acids and convert to TAGs for storage.
What is the difference between a primary and secondary dyslipoproteinaemia?
Primary are inherited errors of metabolism, secondary are acquired secondary to diet, drugs, or an underlying condition like diabetes.
Why do you measure fasting plasma glucose when diagnosing hyperlipoproteinaemias?
Check for fasting
Check for diabetes
What is type 1 hyperlipoproteinaemia?
Defective lipoprotein lipase - chylomicrons in fasting plasma. No link with coronary artery disease.
What is type 2a hyperlipoproteinaemia?
Raised LDL due to defective LDL receptor. Associated with coronary artery disease.
What is type 2b hyperlipoproteinaemia?
High LDL and VLDL, associated with coronary artery disease. Defect unknown.
What is type 3 hyperlipoproteinaemia?
Raised IDL and chylomicron remnants due to defective Apoprotein E - associated with coronary artery disease.
What is type 4 hyperlipoproteinaemia?
Raised VLDL - defect unknown. Associated with coronary artery disease.
What is type 5 hyperlipoproteinaemia?
Raised fasting chylomicrons and VLDLs in fasting plasma - defect unknown. Associated with coronary artery disease.
How would you treat hyperlipoproteinaemia?
1) diet and lifestyle - reduce intake of cholesterol, and TAGs especially those containing saturated fatty acids.
2) statins inhibit HMG CoA reductase
3) bile salt sequestrants such as cholestyramine increase the rate of disposal of cholesterol by conversion into bile salts in the liver - they bind bile salts in the gut and prevent them being reabsorbed into the hepatic-portal circulation.
What are the effects of statins?
Inhibit cholesterol synthesis by inhibiting activity of HMG CoA reductase.
Increase expression of lipoprotein lipase.
What is lipoprotein lipase? Where is it found? What increases is expression?
Enzyme that catalyses hydrolysis of TAGs from chylomicrons and VLDLs - fatty acids taken up by tissues, glycerol transported to liver.
Found in capillaries in tissues such as adipose and muscle.
Insulin.
What is LCAT?
Lecithin:cholesterol acyltransferase - restores the stability of lipoproteins by esterifying cholesterol from the surface, forming cholesterol esters that make up the core.
Uses fatty acids from lecithin (phophatidylcholine)
What is the consequence of LCAT deficiency?
Unstable lipoproteins of abnormal structure and a failure of lipid transport - lipids are deposited in many tissues, leads to atherosclerosis.
Why do cells prefer to take up cholesterol from plasma lipoproteins?
Allows whole body cholesterol content to be closely controlled.
Which cells can’t synthesise cholesterol from Acetyl CoA?
Erythrocytes
How do cells take up cholesterol?
Cells requiring cholesterol synthesise and express LDL receptors.
These recognise and bind Apo B100.
This is taken into the cell by receptor mediated endocytosis.
It is then subjected to lysosomal digestion - cholesterol esters are then converted to cholesterols, which are either stored as cholesterol esters, or used.
