MIDTERM 04 - Cholesterol, Lipoprotein, and Compound Lipids Metabolism Flashcards by Juan Carlos Cornelio

Contains 27 carbons and a CPPP nucleus; found in cell membranes and lipoproteins

Cholesterol

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Are cholesterols esterified w/ a fatty acid at C3

Cholesteryl esters

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Cholesteryl esters are synthesized by 2 enzymes, __________ and __________ (AL)

Acyl-CoA:cholesterol acyltransferase (ACAT); Lecithin:cholesterol acyltransferase (LCAT)

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Intracellular (ACAT or LCAT)

ACAT

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Extracellular (ACAT or LCAT)

LCAT

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Forms cholesteryl esters in cells (ACAT or LCAT)

ACAT

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Forms cholesteryl esters in lipoproteins, specifically HDL (ACAT or LCAT)

LCAT

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Transfers fatty acid from acyl-CoA (ACAT or LCAT)

ACAT

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Transfers fatty acid from lecithin (ACAT or LCAT)

LCAT

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2 sources of cholesterol (DD)

Diet, De Novo synthesis

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Synthesis that occurs in all tissues; is anabolic and endergonic

De Novo cholesterol synthesis

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2 sites for De Novo cholesterol synthesis (CS)

Cytosol, SER

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Synthesis of mevalonate (Steps in De Novo synthesis)

Step 1

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Conversion of mevalonate to 2 activated isoprenes (Steps in De Novo synthesis)

Step 2

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Condensation of 6 isoprenes to squalene (Steps in De Novo synthesis)

Step 3

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Formation of lanosterol (Steps in De Novo synthesis)

Step 4

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Formation of cholesterol (Steps in De Novo synthesis)

Step 5

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Enzyme involved in formation of acetoacetyl-CoA (Step 1- De Novo synthesis)

Cytosolic thiolase

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Enzyme involved in formation of HMG-CoA (Step 1- De Novo synthesis)

HMG CoA synthase

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Isozyme of HMG CoA synthase involved in cholesterol synthesis (Step 1- De Novo synthesis)

Cytosolic isozyme

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Isozyme of HMG CoA synthase involved in ketogenesis (Step 1- De Novo synthesis)

Mitochondrial isozyme

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Enzyme involved in reduction of HMG CoA to mevalonate (Step 1- De Novo synthesis)

HMG CoA reductase

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Cofactor involved in reduction of HMG CoA to mevalonate (Step 1 - De Novo synthesis)

NADPH

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Rate-limiting step in synthesis of mevalonate (Step 1- De Novo synthesis)

Reduction of HMG CoA to mevalonate

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Isoprene involved in step 2 of De NoVo synthesis

2-methyl-1,3-butadiene

Isopentyl diphosphate - # of carbons (Step 2 - De Novo synthesis)

Dimethylallyl diphosphate - # of carbons (Step 2 - De Novo synthesis)

Geranyl diphosphate - # of carbons (Step 3 - De Novo synthesis)

Farnesyl diphosphate - # of carbons (Step 3 - De Novo synthesis)

Squalene - # of carbons (Step 3 - De Novo synthesis)

Enzyme involved in condensation of dimethylallyl diphosphate and geranyl diphosphate (Step 3 - De Novo synthesis)

Cis-prenyl transferase

Enzyme involved in condensation of 2 farnesyl diphosphates to squalene (Step 3 - De Novo synthesis)

Squalene synthetase

Cofactor involved in condensation of 2 farnesyl diphosphates to squalene (Step 3 - De Novo synthesis)

NADPH

Squalene 2,3-epoxide - # of carbons (Step 4 - De Novo synthesis)

Lanosterol - # of carbons (Step 4 - De Novo synthesis)

Enzyme involved in conversion of squalene to squalene 2,3-epoxide (Step 4 - De Novo synthesis)

Squalene epoxidase

Enzyme involved in cyclization of squalene 2,3-epoxide to lanosterol (Step 4 - De Novo synthesis)

Oxidosqualene-lanosterol cyclase

Desmethyl lanosterol - # of carbons (Step 5 - De Novo synthesis)

Zymosterol - # of carbons (Step 5 - De Novo synthesis)

Desmosterol/24-dehydrocholesterol - # of carbons (Step 5 - De Novo synthesis)

Cholesterol - # of carbons (Step 5 - De Novo synthesis)

Enzyme involved in the removal of double bond in the side chain of desmosterol (Step 5 - De Novo synthesis)

Δ24-reductase

Formed from farnesyl diphosphate (Branch points in cholesterol synthesis) (DU)

Dolichol, Ubiquinone

Process that facilitates the anchoring of proteins into lipoid membranes

Protein prenylation

Proteins prenylated with farnesyl or geranylgeranyl residues

GTP-binding proteins

Formed by ACAT; secreted by the liver (Fate of cholesterol)

Cholesteryl esters

Salts that are secreted into the bile and stored in the gallbladder; aids in digestion of dietary lipids (Fate of cholesterol)

Bile salts

2 types of bile salts (CC)

Chenocholate, Cholate

Cholesterol that enters gut lumen via the biliary tract (Fate of cholesterol)

Biliary cholesterol

Regulation of cholesterol synthesis occurs mainly at the ___________ step

HMG-CoA reductase

Increases HMG-CoA reductase activity (Activators of cholesterol synthesis) (IT)

Insulin, Thyroid hormone

Is cAMP-dependent (Activators of cholesterol synthesis)

Dephosphorylation

Involved in product inhibition (Inhibitors of cholesterol synthesis)

Mevalonate

Involved in feedback inhibition (Inhibitors of cholesterol synthesis)

Cholesterol

Inhibits SREBP (Inhibitors of cholesterol synthesis)

Insulin-induced gene (Insig)

Decreases HMG-CoA reductase activity (Inhibitors of cholesterol synthesis) (GG)

Glucagon, Glucocorticoids

Formerly known as HMG-CoA reductase kinase (Inhibitors of cholesterol synthesis)

AMP-activated protein kinase (AMPK)

Phosphorylates and activates AMPK (Inhibitors of cholesterol synthesis)

AMPKK

Cholesterol excretion is via the __________

Bile

The principal sterol in the feces; formed from cholesterol by the bacteria in the lower intestine

Coprostanol

Proteins that are spherical macromolecular complexes made up of a hydrophobic core, amphipathic/hydrophilic shell, and cholesterol

Lipoproteins

Largest and least dense lipoprotein; carry dietary fatty acids to tissues (Major lipoproteins)

Chylomicrons

Carry endogenous fatty acids from the liver into extrahepatic tissues (Major lipoproteins)

Very low density lipoprotein (VLDL)

Condition known as "fatty liver"; occurs when there is an imbalance between hepatic TAG synthesis and secretion of VLDL

Hepatic steatosis

Delivers cholesterol to extrahepatic tissues; also known as "bad cholesterol" (Major lipoproteins)

Low density lipoprotein (LDL)

Delivers cholesterol from extrahepatic tissues to liver; also known as "good cholesterol" (Major lipoproteins)

High density lipoprotein (HDL)

Reaction responsible for virtually all plasma cholesteryl ester

LCAT reaction

Facilitates transfer of cholesteryl ester from HDL to VLDL, IDL, and LDL in exchange for triacylglycerol (Major lipoproteins)

Cholesteryl ester transfer protein (CETP)

Esters of fatty acids with alcohols (Types of lipids)

Simple lipids

Esters of fatty acids with alcohols and other groups (Types of lipids)

Compound lipids

Products of hydrolysis of simple and compound lipids (Types of lipids)

Derived lipids

Composed of phosphatidic acid + alcohol (Compound lipids based on backbone)

Phosphoacylglycerols/Glycerophospholipids

Composed of sphingosine + long chain fatty acid + polar group (Compound lipids based on backbone)

Sphingolipids

Contains phosphate (Compound lipids based on their groups present)

Phospholipids

Contains sugar with ceramide backbone (Compound lipids based on their groups present)

Glycosphingolipids

Phosphoacylglycerols are degraded by ___________

Phospholipases

Sphingomyelin is degraded by __________

Sphingomyelinase