Exam 1 Flashcards
What enzyme initiates bile acid synthesis from cholesterol?
cholesterol 7α-hydroxylase
What 3 things decrease activity HMG-CoA reductase?
- Glucagon
- Epinephrine
- AMPK
What upregulates HMG-CoA reductase?
Low cellular sterol level - SREBP dissociates from SCAP moves to nucleus (TF)
What are 4 mechanisms for regulating cholesterol synthesis and transport?
- Covalent modification of HMG-CoA reductase
- Transcriptional regulation of HMG-CoA reductase
- Activation of ACAT - storage
- Transcriptional regulation of LDL-R
SR-B1 expression is _________ with regards to atherosclerosis.
Protective
PLTP
- Catalyzes transfer of phospholipids between lipoprotein classes
- Needed for maximal activity of LCAT (HDL)
What tissues express ABCG1 and what is its function?
- Spleen, thymus, lung, brain, liver, and macrophages
2. Promotes cholesterol efflux to HDL
Absence of ABCA1 (Tangier Disease) results in what?
- Near-absence of normal HDL particles - no discoidal or spherical HDL
ABCA1 helps release ____________ to apoA1 to make ________.
- Free cholesterol
2. Discoidal HDL
Lp(a)
LDL-like where apoB-100 is covalently bound to apolipoprotein(a) - variable due to Kringle IV repeats in LPA gene
Lp(a) is a _____________ for cardiovascular disease.
Risk factor
What is the most effective way to modulate plasma LDL-C levels?
Manipulation of hepatic LDL-R gene expression
Thyroxine and ________ enhance LDL-R gene expression.
Estrogen
VLDL remnants become IDL and LDL. C apolipoproteins and ______ redistribute to _____.
- ApoE
2. HDL
ACAT-1 is to ________ as ACAT-2 is to liver and intestine.
Macrophages, foam cells, adrenocortical cells and skin
Mutations in ABCG5/G8 cause what disease?
Sitosterolemia - absorb unusually large amounts of plant sterols - tendon and subcutaneous xanthomas
Where does ezetimibe act?
Blocks NPC1L1 to prevent cholesterol absorption in the intestine.
ASCVD
Heart attacks, strokes, and peripheral artery disease
CAD
Coronary atherosclerosis disease
Lipid disorders that cause ASCVD (4)
- Elevated TC or LDL
- Excess apoB lipoproteins - metabolic syndrome/Familial Hyperchol
- Depressed HDL
- Elevated Lp(a)
Lowering LDL with ______ lowers risk.
Statins
Reduced action of SLCO1B1 can lead to what?
Dec. hepatic uptake and Inc. statin concentration in the blood
What is the only mechanism for cholesterol excretion?
Conversion to bile salts
What converts fibrinogen to fibrin(glue)?
Thrombin