Term
| sources of cholesterol (2) |
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Definition
| endogenous synthesis and animal products in diet |
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Term
| cholesterol functions (3) |
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Definition
| cell membranes, steroid hormones, bile acids |
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Term
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Definition
| steroid nucleus w/ hydrocarbon tail and FA tail |
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Term
| lipoproteins transport (2) |
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Definition
| cholesterol esters and triglyceride |
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Term
| storage form of cholesterol? |
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Definition
| CE; not found in cell membranes |
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Term
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Definition
| acyl coa cholesterol acyltransferase - transfers long chain FFA (free fatty acids) to C3 carbon on cholesterol for CE storage in cells |
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Term
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Definition
| 2acetyl coa> acetoacetyl coa+acetyl coa> HMG Coa> mevalonic acid >>>>>>>> cholesterol. 1. thiolase, 2. HMG coa synthase, 3. HMG coa reductase |
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Term
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Definition
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Term
| rate limiting step in cholesterol synthesis (2) |
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Definition
| HMG coa reductase; requires NADPH |
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Term
| where do statins inhibit? |
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Definition
| at HMG coa reductase, via competitive inhibition |
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Term
| where does cholesterol synthesis occur? |
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Definition
| 10-20% in liver, but in all tissues |
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Term
| gene expression of HMG coa reductase controlled by |
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Definition
| insulin and SREBP - high cholesterol levels inhibit SREBP and vice versa, so increased cholesterol decreases stability of the enzyme and phosphorylation decreases its activity |
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Term
| how much free cholesterol (FC) in gi tract excreted |
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Definition
| 50%; 50 sent back to liver |
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Term
| cholesterol is metabolized to _____ by _____ |
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Definition
| bile acid (cholic acid); 7-alpha-hydroxylase. conjugated with glycine or taurine (ratio 3:1) to form bile salt, then secreted in bile to GI tract for micelle formation |
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Term
| percent of bile salts excreted? |
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Definition
| 3%. 97% returned to liver via enterohepatic circulation |
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Term
| what inhibits reabsorption of bile acids (2) |
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Definition
| bile acid-binding resins, dietary fiber |
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Term
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Definition
| shell = unesterified cholesterol, apoprotein and phospholipid. inside = TG and CE, fat-soluble vitamins. (function of lipoproteins is to carry these things around) apoproteins are SPECIFIC in binding and enzyme activation |
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Term
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Definition
| 90% TG, apoprotein B48, metabolized to CM-remnants |
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Term
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Definition
| mostly TG but some CE; apoproteins B100 and E; metabolized to IDL and VLDL remnants |
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Term
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Definition
| allows something to be taken up by the liver |
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Term
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Definition
| 60% cholesterol (esters); apoprotein B100; metabolized FROM IDL and binds LDL receptor |
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Term
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Definition
| carries CE and proteins; apoproteins A C E; key in reverse cholesterol transport and synthesis of other lipoproteins |
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Term
| CM remnant / IDL apoproteins |
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Definition
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Term
| chylomicrons from the intestine follow these pathways |
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Definition
| intestine>mesenteric lymph>thoracic duct>blood > LipoProtein Lipase uses ApoCII as a cofactor to metabolize it > 1. CM-remnant goes to liver, which is mediated by ApoE. 2. CM-remnant enters as FFA into peripheral tissue. |
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Term
| ApoE - what kinds of mutations? |
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Definition
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Term
| cholesterol ester transfer protein |
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Definition
| HDL offers a CE in exchange for TG from VLDL, so that VLDL can make LDL |
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Term
| IDL ___________ by (2) to become LDL |
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Definition
| hydrolyzed; LPL and Hepatic Lipase |
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Term
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Definition
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Term
| HDL gives WHAT to VLDL for further cholesterol synthesis? |
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Definition
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Term
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Definition
| cofactor for LipoProtein Lipase to break down cholesterol precursors / autosomal recessive |
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Term
| VLDL synthesized how, regulated by what |
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Definition
| synthesized in liver from TG; regulated by FFA influx, alcohol, drugs |
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Term
| know VLDL>IDL>LDL diagram |
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Definition
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Term
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Definition
| anchors LPL to capillary walls |
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Term
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Definition
| hydrolyzes TG from CM VLDL and IDL into FFA and glycerol |
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Term
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Definition
| adipose enzyme has high Km for excess storage, cardiac enzyme has small Km because heart prefers that type of energy. (active form is a dimer) |
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Term
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Definition
| regulated by insulin, activated by fibrate drugs |
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Term
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Definition
| autosomal recessive: sky high chylomicrons/TG after birth. must restrict long chain fats in diet |
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Term
| LDL delivers cholesterol to tissues by |
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Definition
| apoB100 binding to LDL receptor (LDLR) and endocytosis |
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Term
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Definition
| in endothelial plaques = oxidized LDL taken up by scavenger receptor macrophages |
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Term
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Definition
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Term
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Definition
| modified LDL w/ Apo(a) linked to ApoB100 via disulfide bond; correlates with CVD because apo(a) is homologous to plasminogen and promotes thrombosis |
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Term
| LDL receptor / regulation |
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Definition
| glycoprotein binds apoB100 and apoE, not apoB48. ligand binding causes endocytosis. gene expression controlled by SREBP (like HMG Coa Reductase) |
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Term
| LDL Receptor-Related Protein (LRP) |
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Definition
| 4LDLR that binds ApoE enriched particles (CM and VLDL remnants), NOT LDL |
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Term
| Familial Hypercholesterolemia |
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Definition
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Term
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Definition
| = nascent HDL = in liver/intestines. contains PL and ApoAI. acquires free cholesterol from cells via ABCA1. LCAT forms CE+PL to make mature HDL (FC+PL>CE) |
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Term
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Definition
| structural protein, LCAT cofactor (LCAT fuses CE and phospholipids to make mature HDL from nHDL and FC - FC+PL>CE), binds SR-B1 on liver, adrenal, gonads |
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Term
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Definition
| HDL receptor = scavenger receptor B1. ApoAI binds it on the liver, adrenal, gonads, and then it accepts CE from mature HDL |
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Term
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Definition
| inhibits CETP (cholesterol ester transfer protein, which exchanges CE for TG with HDL to make LDL from IDL) and HL (hepatic lipase, which hydrolyzes IDL to LDL along with LPL=lipoprotein lipase), stimulates LCAT (which forms mature HDL from CE and PL) |
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Term
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Definition
| 1. hydrolyzes IDL to LDL along with LPL; 2. TG hydrolysis produces small HDL3 from larger HDL2 - acts on HDL to remove TG, PL, and may increase clearance. (this enzyme is cleared by kidney). INSULIN inhibits this enzyme. |
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Term
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Definition
| ATP binding cassette transporter: transports FC out of cells to be picked up by HDL |
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Term
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Definition
| attaches to CM, synthesized in the intestine, structural function |
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Term
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Definition
| attaches to CM remnants, VLDL, IDL; synthesized in liver/anywhere; is a ligand for LDLR and CM remnant receptor |
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Term
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Definition
| attaches to VLDL, IDL, LDL; synthesized in liver; is LDLR ligand and also structural |
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Term
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Definition
| attach to HDL (CM), synthesized in liver and intestine, structural protein and also cofactor for LCAT and HL |
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Term
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Definition
| lipoprotein: HDL>CM, VLDL, IDL. synthesized in liver, is LPL cofactor |
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Term
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Definition
| source: small intestine (diet), destination: tissues (remnant to liver), function: transport exogenous TG |
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Term
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Definition
| source: liver, destination: tissues (converted to IDL), function: transport endogenous TG |
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Term
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Definition
| source: IDL, destination: tissues and liver, function: transport cholesterol |
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Term
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Definition
| source: liver, destination: tissues and liver, function: reverse cholesterol transport |
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Term
| fasting sample eliminates |
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Definition
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Term
| total cholesterol indicates |
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Definition
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Term
| triglyceride measurement indicates |
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Definition
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Term
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Definition
| directly, after precipitation of ApoB100-containing proteins (VLDL, IDL, LDL) |
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Term
| T/F: LDL in a standard lipid profile is an estimation |
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Definition
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Term
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Definition
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Term
| TG restriction for fasting lipid profile |
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Definition
| <400mg/dl, but best at <250mg/dl |
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Term
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Definition
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Term
| TC, TG, HDL, LDL standard values |
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Definition
| TC<200, TG<150, HDL>40, LDL<130 |
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Term
| Type I lipoprotein disorder |
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Definition
| elevated chylomicrons because can't make VLDL because of mutation in LPL gene |
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Term
| type IIa lipoprotein disorder |
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Definition
| familial hypercholesterolemia - elevated LDL |
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Term
| type IIB lipoprotein disorder |
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Definition
| familial combined hyperlipidemia - elevated LDL and VLDL |
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Term
| lipoprotein disorders associated with premature vascular disease |
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Definition
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Term
| lipoprotein disorders associated with pancreatitis |
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Definition
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Term
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Definition
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Term
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Definition
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Term
| factors affecting LDL blood levels (5) |
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Definition
| increased VLDL synthesis, down-regulation of LDLR, increased ApoE-containing particles that compete for the LDLR, defective or decreased expression of LDLR, defective ApoB100 |
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Term
| increased VLDL synthesis (3) |
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Definition
| familial combined hyperlipidemia, polygenic familial hypertriglyceridemia, dietary FFA |
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Term
| familial combined hyperlipidemia |
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Definition
| autosomal dominant 1/200, type II disorder, elevated LDL and VLDL |
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Term
| familial dysbetalipoproteinemia |
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Definition
| increased ApoE-containing particles competing for LDLR |
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Term
| down-regulation of LDLR (2) |
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Definition
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Term
| familial hypercholesterolemia |
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Definition
| defective or decreased expression of LDLR (doesn't affect triglycerides) |
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Term
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Definition
| another form of familial hypercholesterolemia |
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Term
| excess calories, fat, cholesterol -> (2) |
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Definition
| 1. increased TG/cholesterol to liver > downregulation of LDLR and overproduction of VLDL, 2. obesity with increased insulin resistance > increased HDL catabolism, decreased LPL activity, VLDL overproduction |
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Term
| dietary management of lipid disorders (4) |
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Definition
| reduce saturated fat and cholesterol; fiber and plant sterols inhibit cholesterol absorption; substitute w/ things like olive oil; exercise and restrict calories to prevent obesity |
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Term
| medical therapy for lipid disorders (5) |
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Definition
| bile acid sequestrants, cholesterol absorption inhibitors, hmg coa reductase inhibitors, niacin, fibrates |
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Term
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Definition
| "resins" decrease reabsorption of bile acids so more cholesterol is excreted; significant GI side effects |
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Term
| cholesterol absorption inhibitors |
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Definition
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Term
| hmg coa reductase inhibitors |
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Definition
| "statins" upregulate LDL receptors (mechanism?); low but serious side effects |
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Term
| niacin as treatment for lipid disorders |
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Definition
| inhibits VLDL secretion; annoying side effects |
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Term
| fibrates as treatment for lipid disorders |
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Definition
| reduce triglycerides via LPL |
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Term
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Definition
| high TG, TC, LDL, fasting glucose, low HDL |
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