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41 Cards in this Set

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Lipoprotein lipase
an enzyme that hydrolyzes lipids in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), into three free fatty acids and one monoacylglycerol molecule. It requires Apo-CII as a cofactor (apoCII is required for activation of LPL).

Lipoprotein lipase is specifically found in endothelial cells lining the capillaries.
WHAT ACTIVATES LPL?
Insulin is known to activate LPL in adipocytes and its placement in the capillary endothelium.
What is the primary apoprotein responsible for activation of LCAT?
ApoAI is the primary apoprotein responsible for activation of LCAT
What apoproteins are synthesized in the intestine?
apoAI and AIV
Since apoB100 vs apoB48 are synthesized from the same gene, what differentiates them?
mRNA editing

apoB48 is produced exclusively by the intestine as a result of tissue-specific expression of an mRNA-editing enzyme activity (editase).

a substitution of thymidine (T) for cytidine (C) at position 6666, which creates a premature stop codon (TAA) in place of a codon for glutamine (CAA) at residue 2153

apoB48 is 48% of apoB100 in size
Result of eating fat in Regulation of Lipoprotein Synthesis
Dietary fat:
induces chylomicron production by the intestine
induces production of VLDL by the liver
Result of eating carbohydrates in Regulation of Lipoprotein Synthesis
Dietary carbohydrates:
increase VLDL production by stimulating fatty acid synthesis and insulin release
Result of eating cholesterol in Regulation of Lipoprotein Synthesis
Dietary Cholesterol:
suppresses expression of LDL receptors ; important determinant of plasma LDL levels
LDL Clearance
40% of plasma LDL is cleared by the liver

70% of LDL clearance is mediated by LDL receptors
LDL clearnace:
Internalization and degradation of LDL by cells cause........
1) increased intracellular cholesterol (which suppresses HMGCoA reductase activity (the rate-limiting enzyme in cholesterol synthesis))
2) stimulates acyl CoA: cholesterol acyltransferase (ACAT) activity (the intracellular cholesterol-esterifying enzyme)
3) suppresses LDL receptor synthesis
What is the most common cause of accelerated atherosclerosis?
a deficiency of LDL receptors
(prolonged sequestration of lipoproteins next to smooth muscle and endothelial cells leads to oxidative damage of the lipoproteins)
Fatty Acids are converted into molecules of Acetyl CoA in a process called?
BETA OXIDATION
Glycerol formed by lipolysis is absorbed by the liver and phosphorylated, oxidized to dihydroxyacetone phosphate, and then isomerized to.....?
glyceraldehyde 3-phosphate
What hormone is responsible for the breaking down of lipids molecules (not referring to chylomicron or VLDL molecules) in circulation?
Hormone Sensitive Lipase
Lipid synthesis from carb's occurs when citrate is........?
transported out of mito matrix and converted to AcCoA carboxylase, then converted into malonyl CoA by AcCoA carboxylase, then eventually into FA by adding glycerol in Endo Reticulum and transported into circulation
Key regulatory points of lipid synthesis are?
Acetyl CoA and NADH
To make fat, you also need to have carbohydrates, derived from.....?
from a combination of pyruvate and oxaloacetate to form citrate. Remember, citrate is the source of AcCoA for fat synth.
(Note: if oxaloacetate is being used to make energy, it wont be available to build fat)
After Meal Insulin:
1. Inhibits Hormone-sensitive lipase (HSL)
2. Stimulates triglycerides synthesis; FFA+a-glycerol phosphate (inc. with insulin-induced glucose uptake)
3. Stimulates secretion of LPL
stimulates glycolysis (uses glucose for fuel)
4. stimulates glycogenesis (storage of glucose)
5. stimulates FA synthase and AcCoA carboxylase (increases FA synthesis from glucose)

Result: Storage of triglycerides
During Fasting:
1. Plasma glucose dec.
2. Insulin levels decline
3. Drop in insulin activates HSL
4. Triglycerides hydrolyzed in adipocytes
Exogenous Lipid Transport
absorbed by the small intestine; packaged into chylomicrons (large lipoprotein)
Endogenous Lipid Transport
1. Liver synthesizes lipids de novo
2. secreted into the blood as very low-density lipoproteins (VLDL)
_____ and ______ are cleared by the liver, BUT 60% of LDL are cleared by _____________ ?
IDL and LDL; extrahepatic tissues
Reverse Cholesterol Transport
excess cholesterol accumulates in cell membranes of extrahepatic tissues and is returned to the liver via high-density lipoproteins (HDL)
HDL
1) excess cholesterol can accumulate in the cell membranes of extrahepatic tissues and is returned to the liver via high-density lipoproteins (HDL)
2. HDL acquires unesterified (or free) cholesterol
3. lecithin-cholesterol acyltransferase (LCAT) forms cholesterol esters
(transferred from HDL to VLDL by cholesterol ester transfer protein (CETP))
Hepatic cholesterol can be.....?
1. excreted in bile as either bile acids or free cholesterol 2. undergoes reabsorption by the intestine or excretion in the stool
3. hepatic cholesterol can be secreted with new hepatic lipoproteins
cholesterol, triglycerides, cholesterol esters, and phospholipids transported by ....?
LIPOPROTEINS
Apoproteins are either completely or partially exchangeable among lipoprotein except for which apoproteins?
except apoB 100 and B48
Apoproteins are either completely or partially exchangeable among surface phospholipids and cholesterol?
completely transferable
Apoproteins are either completely or partially exchangeable among cholesterol esters and triglycerides ?
Partially transferable and need CETP (cholesterol ester transfer protein)
Which has a greater buoyant density? chylomicrons and VLDL's or LDL and HDL's?
LDL and HDL's (smaller lipoprotein particles)
Chylomicrons
1. most triglyceride-rich (80% is triglyceride) & least dense
2. nearly absent in the fasting state
3. ApoB48 is the major structural protein
4. secreted into intestinal lymph with apoAI and AIV but rapidly lose these in plasma and acquire apoE, CI, CII, and CIII
Very Low-density Lipoproteins (VLDL)
1. produced by the liver
2. During fasting, major carriers of plasma triglycerides
3. apoB100 as their major structural apoprotein
4. Circulating VLDL also may contain apoE, CI, CII, and CIII
Intermediate-density lipoproteins (IDL)
1. 50% of small VLDL are lipolytically converted to IDL
2. contain apoB100
3. enriched in cholesterol esters
4. ApoCs are also lost, whereas apoE is retained (ApoC depleted)
Low-density lipoproteins (LDL)
1. cholesterol-rich
2. account for 70% of the cholesterol in plasma
3. derived from lipolysis of VLDL
4. deliver cholesterol to the artery wall
5. high level of plasma LDL or apoB100 is the best single predictor of increased risk for atherosclerosis
6. oxidation of LDL contributes to atherosclerosis.
Lipoprotein (a) or Lp(a)
LDL particle + Apo (a)
1. (Kringles)
2. Lp(a) level of >40 mg/dl is an independent predictor of coronary artery disease in Caucasians
3. May promote atherosclerosis by competing for plasminogen activation and subsequent lysis of fibrin clots
4. impairs receptor-mediated catabolism of the LDL
High-density lipoproteins (HDL)
1. associated with several minor apoproteins and enzymes, including LCAT, CETP, and a phospholipid transfer protein (enzymes involved in reverse cholesterol transport)
2. role in removal of cholesterol from the artery wall
3. high level of HDL cholesterol (or apoAI, the major apoprotein in HDL) is an
important predictor of decreased risk for atherosclerosis.
Cholesterol esterification catalyzed by ........ a9enzyme) ?
lecithin-cholesterol acyltransferase (LCAT)
__________ is the most abundant protein in the α-lipoproteins (HDL), followed by __________
ApoAI, apoAII
_________ is virtually the sole protein in β-lipoproteins (LDL)
ApoB100
What apoprotein that has three common isoforms, directly affect plasma cholesterol levels?
apoE
Where are 3/4 of the apoproteins synthesized? The other 1/4th?
liver, intestine