Lipids and Lipoproteins Flashcards
3 sources of TAGs
Dietary TAG via intestinal cells
De novo TAG in hepatocytes
De novo TAG in adipocytes
TAG synthesis in intestinal cells (3 steps)
Dietary TAG is broken down into MAG and FFA in lumen.
Intestinal cells resynthesize TAG.
TAG is packaged into chylomicron and is released into the thoracic duct.
TAG synthesis in the liver (3)
Glc and glycerol form G3P using different pathways.
FA CoA is added to G3P to eventually form TAG.
TAG is transported in VLDL in the blood.
What is the unique enzyme, found only in the liver, that converts glycerol to G3P?
Glycerol kinase
TAG synthesis in the liver is promoted by what?
Excess carbs.
TAG synthesis in adipocytes
Glucose forms G3P.
FFA is obtained by the breakdown of chylomicrons and VLDL in the blood via capillary lipoprotien lipase.
Together Glc and FFA form TAGs and are store them in the adipocyte.
TAG synthesis in adipocytes is promoted by:
Excess carbs and fats.
Regulation of TAG breakdown
Glucagon, epi, NE, Insulin
Glucagon, NE, epi activate HSL to begin the breakdown of TAG.
Insulin inhibits.
Insulin is released in the fed state. Why would we want to increase fuel in the blood when we are fed?
HSL, LPL, MAG lipase
HSL - TAG to DAG
LPL - DAG to MAG
MAG lipase - MAG to glycerol
These enzymes, along with ATGL, may have affinity for more than one substrate.
Perilipin
Protein that coats lipids droplets in adipocytes and muscle.
Regulate lipolysis by controlling access to HSL.
Why is perilipin a target for obesity?
If perilipin is inhibited, TAGs are much mobilized much easier and can be accessed by its enzymes for breakdown.
Outer and inner shell of lipoproteins
Outer: phospholipids, free cholesterol, apolipoproteins.
Inner: packed with TAGs and cholesterol.
5 basic types of lipoproteins
Chylomicrons VLDL IDL LDL HDL
Largest to smallest, and increasing levels of TAGs, decreasing levels of protein.
Apolipoproteins on chylomicrons (3)
ApoB - 48: facilitates transport.
ApoC - II: activates lipoprotein lipase.
ApoE: facilitates uptake into the liver.
Apolipoproteins of VLDL (3)
ApoB - 100
ApoC - 11
ApoE
Apolipoproteins of IDL (2)
ApoB - 100
ApoE
Apolipoprotein of LDL (1)
ApoB - 100
ApoB - 100 function
Facilitates uptake into cells
Apolipoproteins of HDL (3)
ApoA - I
ApoC - II
ApoE
Chylomicron processing
Chylomicrons are assembled in GI and transported into the lymph.
CLPL hydrolyzes TAGs into glycerol and FFA. ApoC-II is released back to HDL.
Chylomicron is endocytosed by the hepatcoytes via the ApoE receptor.
VLDL, IDL, and LDL processing
Assembled in the bloodstream.
CLPL hydrolyzes TAGs into FFA and glycerol. ApoC-II is released back to HDL. Now it is IDL.
IDL loses more TAGs and ApoE to become LDL.
LDL’s ApoB-100 binds to its receptor on target tissue.
Atherosclerosis
Defect in the ApoB-100 receptor and LDL remains in the blood.
HDL processing
HDL begins as a disk, but as it picks up cholesterol from tissues it becomes spherical. It begins to deliver its apolipoproteins to other lipoproteins in exchange for TAGs
Eventually, it delivers its load to the liver.
Why is HDL good cholesterol?
Scavenges and removes LDL from periphery and transports it to the liver. Is also believed to have an antioxidant effect/anti-inflammatory effect.
Type I hyperlipoproteinemia
Inability to hydrolyze TAGs in chylomicrons and VLDL.
Due to a deficienct in CLPL or ApoC-II.
May present in infancy.
Plasma TAG level > 1000 md/dl.
Major clinical symptom is xanthoma (nodules of lipids around the eyes).
Type II hyperlipoprotienemia
Defect in LDL receptor (cannot participate in receptor-mediated endocytosis) - cannot recognize ApoB-100.
Can cause atherosclerosis.
Untreated homozygous individuals die of CAD very early. Heterozygous develop CAD by age 40.
Patients will need to change their diet, or possibly a liver transplant if severe.
