Term
| Functions of cholesterol and Cholesterol Esters |
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Definition
Stabilizes fluidity of cell membranes
Precursor to steroids, bile.
Ester form abundant in steroid-producing tissues
Free un-esterfied state found in membranes. |
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Term
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Definition
HMG-CoA synthase(cytoplasmic): requires 3 Acetyl CoA
1st committed step: Mevalnic acid synthesis. 2 NADPHs required, release of CoASH (HMG-CoA reductase(ER bound)
Mevalonate -> dimethylally via 3 phosphorylations, 1 decarboxylation
Six 5-c units(dimethyallyl) form 30-C squalene(non phosphorylated) -> lanosterol -> cholesterol |
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Term
| Regulation of Cholesterol synthase by HMG CoA reductase |
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Definition
Cholesterol inhibits at 3 levels:
Feedback inhibition at gene level
Phosphorylation of HMG-CoA redutase
(Activates)
Degradatoin of HMG-CoA reductase
Insulin stimulates HMG-CoA redutase production
Inhibition by AMP-activated protein kinase. Sterols inhibit cholesterol production. |
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Term
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Definition
| Statins: reversible, compeititve inhibitors of HMG-CoA Reductase |
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Term
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Definition
Branched Chain FA derived from plant isoprenoids.
Produces Malformation of myelin in Refums disease (α-hydroxylase deficiency |
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Term
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Definition
Cholesterol -> Cholic acid -> Bile Acid
7-α-hydroxylase introduces –OH group in position 7 of cholesterol(Membrane bound enzyme) committed 1st step in bile acid synthesis
Requires O2, NADPH, Cytochrome P-450, Ascorbic Acid |
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Term
| Control of bile acid production |
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Definition
Inhibition:
Bile acids/salts: inhibit transcription of 7α-hydroxylase and HMG-reductase
Activatoin:
Dietary cholesterol increases transcription of 7α-hydroxylase
Cholesterol inhibits HMG-CoA reductase
Thyroid hormoens induce synthesis of 7α-hydroxylase |
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Term
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Definition
GLycocholic and taurocholic acid(So3- group of taurine)
Taurine synthesized from Cys oxidation of -SH followed by decarboxylation |
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Term
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Definition
Most gallstones consist of cholesterol.
Cholesterol only kept in solution through incorporation into mixed bile micelles
Increase in cholesterol or decrease in bile salts/lecithin -> cholesterol crystals |
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Term
| Digestion of Lipids in Small intestine |
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Definition
Bile salts: glycocholic and taurocholic help create stable micelles.
Lipase adheres to micelle surface.
Pancreatic Lipase ctalyzes hydrolysis of triacylglycerides at 1 & 3 positions forming 1,2-diacyllgycerol and than 2-monoacylglyerol
Colipase required for binding of pancreatic lipase
Xenical(orlistat) inhibits Lipases. |
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Term
| Degradation of cholesterol and phospholipid Esters |
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Definition
Cholesteryl Ester hydrolase(cholesterol esterase): produces cholesterol and FFAs
Phospholipase A2(activated by trypsin) cleaves phospholipid at C-2 -> lysophoshpolipid and 1 FFA
Lysophospholipid cleaved by lysophospholipase -> glycerol-phophoryl base + 1 FFA |
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Term
| Conversion of Long FA into TAGs |
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Definition
Long Chain FFAs and cholesterol are resterified: Requires CoA activation
Fatty acyl CoA synthetase(thiokinase) activates FA, requires ATP -> AMP Irreversible
Fatty Acyl-CoA is now esterfied to TAGs by acyltransferases for packing along with ApoB-48 into chylomicrons |
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Term
| Addition of cholesterol to chylomicrons |
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Definition
| Cholesterol is esterfied to fatty acids, forming cholesteryl esters (Catalyzed by Cholesterol Acyl Transferase-ACAT) |
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Term
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Definition
ApoB-48 is found only in chylomicrons and produced by intestinal cells.
ApoB48: Produced by RNA editing of ApoB-100 Cytosine -> Urasil. Stop codon made.
ApoB-48 and lipids are incorporated into chylomicrons by Microsomal triglyceride transfer protein(MTP) |
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Term
| Apoplipoproteins in Chylomicron |
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Definition
ApoB-48: important for cholesteorl transport
ApoC-II: Activates Lipoprotein Lipase(LPL)
ApoE: triggers clearance of VLDL and chylomicron remnants. Endocytosis into liver. |
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Term
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Definition
Tethered by GPI-anchored high-density lipoprotein binding protein(GPIHBP1)
Myocardial LPL Km is 10 times lower than km of adipose tissue. |
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Term
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Definition
Destinations: Skeletal and cardiac muscle, kidney, adipose tissue. NOT to RBCs or nervous tissue.(no mitochondria)
LPL provides FA to most tissues except brain and liver. |
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Term
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Definition
| Adipose tissue lacks glycerokinase so most glyerol -> liver for glycolysis or gluconeogenesis. |
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Term
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Definition
Bile salts: Shortened hydrocarbon chain by 3 C
Terminal C is oxidized to carboxy group
1-2 more OH groups added in α-configuration
Fusion between A and B rings is in cis- configuration, Bend between rings A & B |
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