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29 Cards in this Set
- Front
- Back
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Rate limiting step of cholesterol synthesis?
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HMG-CoA reduction is the rate limiting step in cholesterol synthesis.
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The rate limiting step in cholesterol synthesis, reduction of HMG-CoA, is catalyzed by which enzyme?
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HMG-CoA reductase
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HMG-CoA is the enzyme that catalyzes the rate limiting step in cholesterol synthesis. How is this regulated?
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-Negative feedback from sterols through SREBP and SCAP (transcription factors)
-Sterols allosterically bind to HMG-CoA and signal them for destruction |
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HMG-CoA is the enzyme that catalyzes the rate limiting step in cholesterol synthesis. What is the effect of glucagon on it's action?
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HMG-CoA reductase is inactive (active when phosphorylated). There is no production of bile or VLDL in fasting/starved state.
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Isoprenoids are metabolic precursors to cholesterol synthesis. Farnesyl pyrophosphate (15C) is formed by combining 3 of what kind of molecule?
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3 isoprenes. Isoprenes are activated 5C units used
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Isoprenes are building blocks for cholesterol. What else can they build?
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Vit E, CoQ 10
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Where are lipids synthesized?
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In the smooth ER
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What is the function of bile salts?
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Solubilize fat
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Cholesterol is used to create bile salts, steroid hormones, and Vit D. Where is bile made?
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Liver
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What are bile salts conjugated with and what effect does this have on their properties?
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-Congugated with taurine and glycine
-Makes them better detergents -More efficiently ionized in the intestines -Highly charged and hydrophobic |
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How bacteria in the gut contribute to the reabsorption of bile salts?
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-Bacteria deconjugate and dehydroxylate bile salts making them less soluble.
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What step in cholesterol synthesis does the statin class of drugs block?
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The reduction of HMG-CoA (Hydroxymethylglutaryl CoA)
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What is the function of lipoproteins?
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-Transport lipids
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What are the 4 lipid classes?
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-Phospholipids
-Cholesterol -Cholesterol esters -Triacylglycerols |
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What are the 3 classes of lipoproteins?
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-Chylomicrons
-VLDL -HDL |
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Chylomicrons transport lipids from the gut to the tissues. They are synthesized in the brush border of the gut and then mature in the lymph. What happens during the maturation process?
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-ApoC is added (activates LPL)
-ApoE is added (returns remnant of chylomicron to the liver) |
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LPL Km has differnent values in different tissues. Explain the Km of cardiac tissue and tell why it's important.
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-Low Km in the heart
-Ensures that FA's are picked up by the heart under conditions where other tissues can't get them. |
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Are there LPL's on the liver?
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No
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What are the size differences between VLDL's and chylomicrons? Where are each made?
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-VLDL's twice as big, made in liver
-Chylomicrons half as big, made in intestines |
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VLDL's must be matured similar to chylomicrons. Where does this maturation occur and what molecule is responsible?
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-Occurs in the blood.
-HDL donates ApoC and ApoE |
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What is the fate of LDL's? (2)
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-LDL receptors in adrenal tissue and gonads --> need cholesterol for steroid hormone synthesis
-Non specific pathway - macrophage take up LDL, get oxidized, form foam cell, etc |
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Why is HDL referred to as the "good cholesterol"?
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-Responsible for reverse transport of cholesterol stuck in macrophages. Takes them back to the liver.
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What is the importance of LCAT (lecithin cholesterol acyl transferase) and HDL?
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Allows HLD to esterify cholesterol into cholesterol ester, making them more hydrophobic and driving them into the core of the HDL or the LDL.
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What is the importance of CETP (cholesterol ester transfer protein) and HDL?
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Allows HLD to trade a TG for a cholesterol ester with a VLDL or a chylomicron.
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What is the enzyme that flips cholesterol into the outer leaf of the cell membrane for HDL to pick it up?
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ABC1 (ATP-binding cassette transporter 1)
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In Tangier disease, ABC1 is defective. What effect would this have on the tissues?
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-Cholesterol builds up in tonsils and other organs
-Reduced efflux of cholesterol from peripheral tissues leads to foam cells, plaque, and premature atherosclerosis. |
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What tissues in the body have LDL receptors?
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-Liver
-Adrenals -Gonads |
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What is the process for LDL to be endocytosed by LDL receptors?
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-LDL receptors are present in clathrin coated pits
-When LDL binds to receptor, the pits pinch off to form clathrin coated vesicles inside the cell. |
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What increases LDL receptor activity? What decreases LDL receptor activity?
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-Insulin increase
-Cholesterol decreases |
