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17 Cards in this Set
- Front
- Back
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What are the sources of cholesterol? |
Half - de nevo Half - diet |
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Site of cholesterol synthesis |
Liver Small intestine |
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What are three broad stages in cholesterol biosynthesis? |
1 - synthesis of an activated isoprene unit 2- condensation of six isoprene units to squalene 3 - squalene cyclises - tetracyclic product - cholesterol |
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What is the first step in cholesterol synthesis? |
Formation of HMG-CoA from acetyl CoA and acetoacetyl CoA
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What is the committed step in cholesterol synthesis? |
HMG-CoA to mevalonate HMG-Co A reductase |
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What is the name of the activated isoprene unit? |
3-isopentenyl pyrophosphate (IPP)
Building block for many biomolecules |
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How much cholesterol is synthesised by an adult on a low-cholesterol diet? |
800 |
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How is HMG-CoA reductase regulated?
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Levels of cholesterol - Low levels, SREBP Tf (Sterol regulatory element binding protein) is activated, transported to nucleus for expression of reductase gene - High levels, SREBP activation blocked, nuclear SREB degraded, reductase gene silenced Metabolites derived from mevalonate inhibits reductase transcription |
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What is the DNA position when high levels of cholesterol?
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SREB anchored in ER by SCAP and Insig proteins |
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What is the DNA position when low levels of cholesterol? |
Dissociates Insig from sterol sensing domain of SCAP SCAP-SREB transported to Golgi Nuclear proteases cleave nuclear SREB |
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How is HMG-CoA reductase regulated? |
Inhibited by phosphorylation AMP-regulated protein kinase switches off enzyme when ATP is low |
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Enzyme for intracellular cholesterol to cholesteryl esters
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ACAT acyl-CoA cholesterol transferase |
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How is cholesterol transported? |
From liver to peripheral tissues - cholesteryl esters in lipoproteins - more hydrophobic than cholesterol - but, cannot be incorporated into membranes ACAT - transfers fatty acid from acyl-CoA to cholesterol |
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What are the functions of the proteins in LP?
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Solubilisation of lipids Cell-targeting signals |
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How are lipoproteins classified?
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Based on density
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Types of lipoproteins
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Chylomicrons - largest, lowest density due to TAG, dietary fat transport VLDL - IDL - LDL - highest % cholesteryl esters HDL - highest protein/lipid ratio |
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What do chylomicrons do?
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Carry dietary fatty acids to peripheral tissues
Chylomicrons remnants carry remaining FAs and cholesterol to liver. Receptors in liver bind ApoE - endocytosis
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