Lipids and Lipoproteins Flashcards
What is precursor for isoprenoids (steroids), lipid soluble vitamins (isoprenoids),& ubiquinone’s?
IPP
Sources oAcetyl coa
Made in mitochondria: • oxidative decarboxylation of pyruvate Beta ox fatty acids • breakdown amino acids transported into cytoplasm via citrate shuttle
How many IPP units form sterne backbone ring?
6
What is alicyclic compound made of?
4 fused rings (sterane) W/ one hydroxyl group at c3
What’s most abundant steroid?
Cholesterol
T or F: Cells can degrade nucleus of cholesterol
False
Biosynthesis of cholesterol is ____ to dietary intake
Inversely proportional
How many nadph ATP & Acetyl coa are used for making cholesterol
16 nadph 18ATP 18 AcetylCoA
Rate limiting enzyme in cholesterol synthesis 2
HMG CoA reductase producing mevalonate & targeted statin, by
Positive regulators of HMG CoA reductase?
Insulin & thyroxine
Negative regulators of HMG CoA reductase?
Glucagon, sterols, high amp, vitamin E, Statins
What type of inhibition does a statin utilize?
Competitive
What is the km for KMG CoA and ki for statins?
Km is 4 uM Ki is 5-45 nM
How do statins lead to myotoxic side effects?
Statin mediated myopathy from deletion of muscle ubquirone (CoQ10)
What happens with cholesterol In regards to CPR?
• Made into ACAT • packed into VLDL
Active form of cholesterol ?
Dephosphorylated
How does insulin activate HMG COA reductase
Dephosphorylates it
Transcriptional control of HMG CoA Reductase?
Binding of TF to promoter
How does low cholesterol impact srebp?
- Triggers translocation of SREBP-SCAP to Golgi
- SREBP is cleaved & n-terminus released
- SREBP tf dimer binds to SRE on HMGR promoter
Inner core lipoproteins?
• Packed W TAGS, cholesterol, cholesterol esters
Outer shell lipoproteins?
•mono-layer phosphiollpid, free cholesterol, & apolipoproteins
Function of lipoproteins?
- Transport & deliver TAGS
- cholesterol homeostasis
- Apolipoproteins act as cell targeting signals & ligand
- lipid metabolism
5 types of lipoproteins?
- Chylomicrons (largest, but smallest density, Most TAGs, least protein)
- VLDL
- IDL
- LDL
- HDL (smallest, but highest density,least TAGs, most protein)
Bad cholesterol?
LDL
Where are chylomicrons formed?
Dietary fats in SI
What does ApoB-48 & ApoE &ApoC-II do where are they found?
- ApoB-48 facilitates transport
- ApoE facilitates uptake to liver
- ApoC-11 activates capillary lipoprotein lipase
- chylomicron’s
Where are VLDL made what are the proteins?
Liver
- •ApoB-100: recognized by receptors in target cells
- •Apoc-11: activates capilllary lipoprotein lipase
- ApoE: promotes heaptic uptake
HDL proteins?
- • ApoA-1 activates enzyme to esterify cholesterol
- ApoC-11: activates capilllary lipoprotein lipase
- ApoE: promotes hepatic upatake
IDL proteins?
- ApoB-100
- ApoE
What apo proteins are found on a nascent chylomicron?
- ApoB-48: promotes transport
What apo proteins are found on the matrue chylomicrons?
- ApoB-48
- Transport
- ApoC-II
- activates capillary lipoprotein lipase
- ApoE
- deliver to liver
Describe VLDL IDL and LDL processing.
- Start with VLDL and capillary lipoprotein lipase hydrolyzes triacylglycerols to glycerol and free fatty acids. ApoCII is released and IDL remains
- IDL gets internalized by liver via ApoE binding hepatocytes.
- Hepatic lipoprotein lipase takes off more triacylglycerols and ApoE to become LDL
- LDL deliver cholesterol to liver and tissues with binding of ApoB-100
Role of LDL? significant Apo protein and core makeup?
- Major carrier of cholesterol in blood to peripheral tissues and regulates de novo synthesis
- Shell has ApoB-100 which is recognized by receptors in targt cells
- Core is packed with 1500 cholesterol esters
What causes familial hypercholesterolemia?
- Receptors on LDL are unable to release LDL cargo
- Cholesterol in LDL is not used
What does LCAT do?
- Gives rise to mature HDL
Function of HDL?
- Crucial for maturation of chylomicrons supplies apo C II and ApoE
- Scavenges and removes LDL and transports it to liver for processing
- “Reverse Cholesterol Transport” brings cholesterol from tissues to liver for excretion
What happens when their is a mutation in ABCA1?
- ABCA1 is a cholesterol transport protin in endothelial cells and macrophages
- Loss of this results in Tangier disease characterized by HDL deficiency accumulation of cholesterol in macrophages and premature atherosclerosis
What cholesterol molecule has antioxidant, anti-inflammatory, antithrombotic, and NO producing properites?
HDL
How do you increase HDL-C levels?
- Weight loss, exercise and smoking cessation
- Antihypercholesterolemic drugs, fibrates, anti-diabetic thiazolidine drugs, estrogens and omega 3 FA
What is type I Hyperlipoproteinemia, cause, sx and tx?
- aka Hyperchylomicronemia
- Inability to hydrolyze TAGs in chylomicrons and VLDL
- Caused by a deficiency in Capillary lipoprotien lipase or ApoC-II
- Sx: Abdominal pain, acute pancreatitis, cutaneous eruptive xanthomas
- Tx: low fat diet
(Autosomal recessive)
With type I hyperlipoproteinemia what are the two deficiencies that cause it?
- ApoC-II deficiency, post adolescence
- Primary LPL deficiency- manifiests in infancy
- Plasma TAG levels are greater than 1000 mg/dL
What is type II hyperlipoproteinemia, cause, genetics, sx, and tratement?
- aka familial hypercholesterolemia
- Caused by defects in LDL receptor resutling in defects in uptake of LDL via receptor mediated endocytosis
- inability to recognize ApoB100 on LDL
- Autosomal Dominant
- Sx: Xanthomas, corneal eye deposits, angina
- Tx:
- heterozygous: responds to diet, statins and bile acid binding resins
- homozygous: need LDL apheresis and liver transplant
In Type II hyperlipoproteinemia (FH), what happens to excess LDL?
- accumulates under endothelial cells lining blood vessesl and undergoes oxidation forming oxLDL
- oxLDL initiates inflammatory response deading to development of atherosclerosis
With type II FH, what happens with untreated homozygous patients?
- Usually die of CAD Dbefore teenage yeaers
