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18 Cards in this Set
- Front
- Back
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What 2 functions does cholesterol serve?
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1-Important for structure. Concentrated in plasma membranes
2-cholesterol is a precursor for hormones |
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What is the primary source of cholesterol in our bodies?
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-we synthesize most of our cholesterol
-Dietary cholesterol has little influence on plasma cholesterol -cholesterol in the body does directly correlate with the number of calories consumed |
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When do we synthesize cholesterol?
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In the fed state, with high levels of insulin.
-lots of acetyl CoA in cytoplasm for fatty acid synthesis |
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What is req'd for cholesterol synthesis?
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High levels of Acetyl CoA in the cytoplasm.
-also need high levels of acetyl coA for fatty acid synthesis -Acetyl CoA is produced from citrate -Contrastingly, Acetyl CoA can be made in the mitochondria from beta oxidation, leading to ketone formation. |
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What is the first step of cholesterol synthesis?
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Condensation of 2 molecules of acetyl coa to form a 4 carbon intermediate using thiolase.
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What is the 2nd step of cholesterol synthesis?
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Condensation of another acetyl CoA and 4carbon intermediate (acetoacetyl coa) using HMG coA synthase to form HMG CoA
-very similar to ketone synthesis but this is taking place in the cytosol NOT the mitochondria like ketone synthesis |
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What is the first PROPER step of the cholesterol synthetic pathway?
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Synthesis of mevalonic acid from HMG CoA using HMG CoA reductase.
-gets hydrogens from 2 NADH -also the rate limiting/most important step |
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What enzyme do statins inhibit?
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HMG CoA reductase
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How is cholesterol distributed to the organism?
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Through incorporation into vLDL particles, but first cholesterol has to be esterified
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What is ACAT?
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Acyl Cholesterol Acyl Transferase
-uses acyl CoA to esterify acyl transferase |
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Where does cholesterol ester packaging for transport take place?
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On the ER in the liver, then follows through the normal secretory pathway
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Why is LDL bad cholesterol?
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Chronic overnutrition. Cholesterol is a surrogate for indicating chronic overnutrition
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What is reverse transport?
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-tissues saturated w/more cholesterol than they need, HDL gets cholesterol out.
-HDL is made in the liver, but is lipid poor -Acts like a lipid sponge as it circulates, picking up more and more cholesterol -takes cholesterol back to liver where it can be used in other ways such as making bile acids -Liver has a specific receptor for HDL |
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What are the 3 components involved in regulating cholesterol synthesis?
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HMG CoA Synthase
HMG CoA Reductase LDL receptors -regulation of these factors occurs at the transcriptional level which controls how much enzyme is present |
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What molecule is involved in the transcriptional regulation of cholesterol?
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SREBP is the transcription factor that regulates the expression of HMG CoA reductase.
-Low cholesterol, high SREBP -High cholesterol, low SREBP |
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How does the transcription regulation of cholesterol sense cholesterol?
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-SREBP is synthesized as a transmembrane protein.
-SREBP is held in the ER b/c of interaction w/ SCAP -If cholesterol is present, SCAP will stay in the ER -if cholesterol is low, SCAP will move to the Golgi. In the golgi, SCAP will interact with proteins and go forward |
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What besides HMG CoA reductase does SREBP control?
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LDL receptor expression!
-If cell has no cholesterol, it will upregulate its LDL receptor, to take up more LDL. |
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Statins reduce the circulating presence of what molecules?
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Cholesterol and TAGS!
-statins trick the cell into making it think it does not have enough cholesterol |
