Lipid Metabolism
Exogenous
Dietary lipids are
absorbed in the intestines
Lipids are broken down by lipase into triglycerides and cholesterol
Triglycerides and cholesterol bind using apoprotein "C" to form chylomicrons
Chylomicrons enter lymphatic system and travel to peripheral tissue
Once chylomicrons are in peripheral tissue, lipoprotein lipase can breakdown further...
Free fatty acids can be used as energy
Triglycerides can be stored in adipose tissue
Left over "pieces" known as remnants of chylomicrons show apoprotein "E" and are brought back to the liver
Apolipoprotein B-48 regulates secretion into lymph
Endogenous
Liver uses stored triglycerides and cholesterol to form VLDL
Glucose absorbed by the liver is broken down with the use of HMG-C0A reductase to form cholesterol
Synthesis of triglycerides and cholesterol form VLDL
VLDL enters bloodstream
VLDL turns into IDL by lipoprotein lipase
Remnants of broken down VLDL are cleared by circulation or combined with LDL
IDL is converted to LDL
LDL contain a cholesterol core and triglycerides
Cholesterol is dropped off at tissues to help with cellular function such as hormone formation and form the cell membrane
LDL then travels back to the liver to be reabsorbed and can be either...
Recycled and turned back into lipoproteins
Excreted in the form of bile
Free fatty acids liberated from VLDL are stored or used as energy
Normal lipid levels
Reverse cholesterol pathway
"Empty" HDL particles are secreated by the liver into the blood stream to "pick-up" free cholesterol
HDL then combines with cholesteryl esters
Cholesterol is picked up by HDL from macrophages via ABCA1
HDL can also deposit cholesterol into LDL via CETP
Pharmacological treatment
Chylomicrons: Transport lipids from food (exogenous)
VLDL: Transport endogenous triglycerides to tissues
HDL: Picks up cholesterol from tissue and transports it
LDL: Transport cholesterol
total choleterol <200mg/dL
triglycerides <150mg/dL
HDL <50mg/dL
LDL<100mg/dL
HDL particles circulate back to the liver and enter through SR-B1 or scavenger site where excess cholesterol is...
Deposited into tissue
Secreted in the form of bile
Statins
(HMG_CoA reductase inhibitor)
Inhibits HMG-CoA reductase to form cholesterol in the liver
Increase absorption of LDL and triglycerides while increasing HDL
Atorvastatin (Lipitor)
Fluvastatin (Lescol XL)
Lovastatin (Altoprev)
Pravastatin (Pravachol)
Rosuvastatin (Crestor)
Simvastatin (Zocor)
Can increase blood sugar in diabetic patients
Bile-acid-binding resins
Bind with cholesterol containing bile in the intestines which increases the removal of cholesterol by bodily secreation
Cholestyramine (Prevalite)
Colesevelam (Welchol)
Colestipol (Colestid)
Used in conjunction with statins
Cholesterol absorption inhibitor agent
Acts in the small intestines to reduce the absorption of cholesterol
Decreases circulating cholesterol that would be transferred back to the liver--decreasing hepatic cholesterol levels
Ezetimibe (Zetia)
Commonly used in conjunction with statins
Niacin
Inhibits synthesis of VLDL in the liver
Leads to decreased LDL and triglyceride levels
Increases HDL levels up 35%
Niacin, vitamin B12, Prescription Niacor
Fibrates
Stimulates lipoprotein lipase causing a decrease in triglycerides
Decrease in triglycerides, increases circulating HDL
Fenofibrate (Antara, Lipofen)
Gemfibrozil (Lopid)