26. Lipids & Lipoproteins Flashcards
How are isoprenoids formed
3 acetyl CoA —> isopentenyl pyrophos (IPP) = which are building blocs for isoprenoids
What are the sources of acetyl CoA
Oxidative decarbox of pyruvate
betaa ox of FA
Breakdown of AA
(All in mitochondria)
What is the structure of cholesterol
Alicyclic compound w/ 27 Cs
-sterane ring, 8 C hydrocarbon, 2 methyl groups, 1 double bond and 1 -OH group
what compounds is cholesterol a precursor for
bile acirs & bile salts
vit D
steroid hormones
what is the rate limiting step for cholesterol synthesis
HMG CoA reductase
what can IPP form
steroids
lipid soluble vitamins
others like ubiquinone & lipid anchors
what inhibits the conversion of lanosterol to cholesterol
antifungal agents (miconazole)
tamoxifen
what medications inhibit HMG CoA reductase
statins (comp inhibitor)
-which have higher affinity than the natural molecule
why do statins have myotoxic side effects
also end up inhibiting the formation of ubiquinone –> impair mitochondria fxn
what is the “fate” of cholesterol
cholesterol esterfied by ACAT
packaged inot VLDL & released into blood
& more
what happens to cholesterol formation in fed state
reduced bc glucagon inhibits HMG CoA by phosphorylating it
what happens to transcription with low sterol
promote release of SREBP-SCAP from ER to golgi –>
proteolysis and release mature SREBP to dimerize & translocate to nucleus –>
binds to SRE and promotes transcription of HMG CoA Reductase
what are lipoproteins
vehicles for transport of cholesterol, cholesterol esters, TAGs, & fat soluble Vits
=chylomicrons, VLDL, IDL, LDL, HDL
how do lipoproteins contribute to lipid metabolism
- transport and deliver TAGs
- cholesterol homeostasis by transporting it to liver
- apolipoprotein –> target signals/ligands to internalize receptors
- apolipoproteins–> activate enzymes
what cell markers do chylomicrons have and what are the fxns
ApoB-48 - facilitate transport
ApoC-II - activate cap lipoprotein lipase (CLPL)
ApoE - facilitates uptate into liver
what are the biomarkers on VLDL, IDL & LDL
VLDL - ApoB-100, ApoC-II, ApoE
IDL - ApoB-100, ApoE
LDL- ApoB-100
what biomarkers are on HDL & what are their fxns
ApoA-I - activate enzyme that esterfy cholesterol
ApoC-II -activate CLPL
ApoE - promote uptake into liver
what are the steps of processing chylomicrons
- immature chylomicrons (dietary lipids) in SI travel thru blood
- HDL donate ApoC-II & ApoE –> mature
- CPLP hydrolyze TAG into glycerol & FFA (release ApoC
- remaining endocytosed by liver - bind ApoE
explain the processing of VLDL, IDL & LDL
- VLDL made in liver –> blood
- CLPL hydrolyze TAG into glycerol & FA (release ApoC-II) –> IDL
- IDL deliverd to liver (use ApoE) & lose more TAGs & ApoE –> LD
- LDL deliver cholesterol to liver and peripheral tissue using ApoB-100
what is the uptake mechanism for LDL
ApoB-100 bind target cell –>
internalize into cell –> make vesicle –>
decrease pH in vescile –> LDL seperates out –>
send to lysosome for breakdown –> get cholesterol & AA
What are the steps for the processing of HDL
- immature disc shaped HDL made in liver & SI
- pick up cholesteol from peripheral tissues
- LCAT esterfy cholesterol –> cholesterol ester enter HDL core
- HDL donates and receives ApoC-II & ApoE, transfer esters to VLDL, IDL & LDL & deliver cholesterol to liver
what are the benefits of HDL
reduce risk fo CAD
- reverse cholesterol transport - take up cholesterol from tissues and deliver to liver for excretio
- antioxidant, anti-inflam, anti-throm & NO inducing
- inhibit oxidation of LDL
what occurs with ABCA1 mutation
inactivate cholestrol-transport protein in endothelial cells & macrophages
unable to transport LDL –> accumulate cholesterol in macrophage –> premature athresclerosis
=Tangier disease
what increases HDL
exercise
weight loss
quitting smoking
What is type I hyperlipoproteinemia
inability to hydrolyze TAG in chylomicron & VLDL
-deficient CLPL (infants) or ApoC-II (teens)
TAG > 1000 mg/dL –> cream color in blood sample
present with abd pain, acure pancreatitis, cutaneous eruptive xanthomas
What is type II hyperlipoproteinemia
familial hypercholesterolemia
deficient LDL receptor (cant recognize ApoC 100) –> increase cholesterol in blood –> oxidize LDL –> inflam response –> artherosclerosis
symptoms: xanthomas, angina pectoris
how does atherosclerosis form
LDL-C accumulate –> oxidize –> accumulate in vessel wall –>
endothelial injury –> influz of LDL into arterial wall
–> inflam response from oxLDL –> macrophages become foams cells –> form plaques
