Cells in the intestine use 2-monoacylglycerol (2-MAG) as a backbone to synthesize fatty acids. What do hepatocytes use as a backbone for fatty acid synthesis?
Activated glycerol.
Nascent lipoproteins in the liver are associated with which lipoprotein?
ApoB-100.
What is the difference between ApoB-100 and ApoB-48?
Both are synthesized from the same gene but ApoB-48 is truncated because the DNA in the intestine is edited so that it contains a premature stop codon.
What is the difference between chylomicrons and very low density lipoprotein (VLDL)?
Chylomicrons are bigger and have a lower cholesterol esters to TAG ratio.
Where in the body and from what lipoprotein does very low density lipoprotein (VLDL) acquire ApoC-II?
In the blood after it is secreted by the liver, and it acquires ApoC-II from high density lipoprotein (HDL).
What is the approximate half-life of very low density lipoprotein (VLDL)?
2-4 hours.
What does very low density lipoprotein (VLDL) become when it loses ApoC-II?
Intermediate density lipoprotein (IDL).
Which apoproteins are present on mature very low density lipoproteins (VLDL)?
ApoB-100, ApoC-II and ApoE.
What is the function of ApoC-II?
It serves as a substrate for lipoprotein lipase.
What are the two fates of intermediate density lipoprotein (IDL)?
1) It can be depleted of triacylglycerols (TAGs) on the surface of hepatocytes by hepatic triacylglycerol lipase (HTGL), lose ApoE and become low density lipoprotein (LDL). 2) Alternatively, it can retain ApoE, bind to LDL receptors on liver cells with th
What is the major serum transporter of cholesterol?
Low density lipoprotein (LDL). Note that cholesterol is transported in the form of cholesterol esters.
Which lipoprotein(s) are present in low density lipoprotein (LDL)?
Only ApoB-100.
Where are the majority of low density lipoprotein (LDL) receptors found?
On hepatocytes. They may also be found on cells that require cholesterol such as those that produce steroid hormones like in the adrenal glands or sex organs.
What is the approximate half-life of low density lipoprotein (LDL)?
About 3 days.
What is the function of lipoprotein lipase (LPL)?
It hydrolyzes triacylglycerols (TAGs) on very low density lipoprotein (VLDL) into fatty acids.
Which form of cholesterol is a major risk factor for heart disease?
Low density lipoprotein (LDL).
Why is the presence of oxidized low density lipoprotein (LDL) in plasma injurious?
It stimulates endothelial cells to express adhesion molecules that attract monocytes. The monocytes then differentiate into mature monocytes, ingest oxidized LDL, become foam cells and die. This promotes smooth muscle growth and plaque formation in the va
True or False. Oxidized low density lipoproteins (LDL) are phagocytozed by mature macrophages.
False. Oxidized LDL binds to a scavenger receptor on the macrophages.
Where is high density lipoprotein (HDL) synthesized?
In the liver and intestine.
Which apolipoprotein(s) are present in high density liproteins (HDL)?
ApoA-I, ApoC-II and ApoE.
What is the main function of high density lipoprotein (HDL) with regards to cholesterol transport in blood?
HDL removes excess cholesterol when it encounters various cells throughout the body and transports it in the form of cholesterol esters to other tissues that need cholesterol. It also exchanges cholesterol esters for TAGs with chylomicrons, VLDL and IDL.
True or False. High density lipoprotein (HDL) is associated with heart disease.
False. HDL and heart disease are negatively correlated.
What is the function of ApoA-I?
It stimulates serum lecithin-cholesterol acyl transferase (LCAT).
What is the reaction catalyzed by serum lecithin-cholesterol acyl transferase (LCAT)?
LCAT esterifies cell membrane cholesterol to form cholesterol esters. Note that the fatty acid esterified to cholesterol does not come from a triacylglyerol. It comes from a membrane phospholipid.
What is the function of cholesterol ester transfer protein (CETP)?
It catalyzes the exchange of TAGs from chylomicrons, VLDL, or IDL with cholesterol esters on HDL.
What is the receptor for high density lipoprotein (HDL)?
It is thought to be scavenger receptor B1 (SR-BI).
What are two causes of hyperlipoproteinemias?
Excess production or decreased utilization of lipoproteins.
What is the main cause of hypobetalipoproteinemia?
Genetic defect in the ApoB gene. This is associated with deficiency of chylomicrons, VLDL and LDL.
HDL deficiency is associated with what condition?
Tangier disease.
What is the role of epinephrine and glucagon in fatty acid metabolism?
They are released when the body needs energy and activate a cAMP-dependent pathway that results in Protein kinase A (PKA) activation. PKA then inactivates acetyl-CoA carboxylase (blocks fatty acid synthesis) and stimulates hormone-sensitive lipase, HSL (c
Fatty acids can be carried on what blood protein?
Serum albumin.
What reaction is catalyzed by fatty acyl CoA synthetase?
Activation of a fatty acid by converting it to an acyl-CoA.
Where in the cell does activation of fatty acids occur?
In the ER or outer mitochondrial membrane.
Where in the cell does beta-oxidation of fatty acids occur?
In the mitochondrial matrix.
Acyl-CoA's cannot cross the mitochondrial membrane. In what form are they transported instead?
As acyl-carnitine.
What is the major regulatory step in fatty acid oxidation?
Conversion of acyl-CoA to acyl-carnitine by carnitine acyltransferase I (CAT-I).
What is the inhibitor of carnitine acyltransferase I (CAT-I)?
Malonyl-CoA.
Where in the cell does the carnitine acyltransferase I (CAT-I) reaction occur?
On the cytoplasmic side of the inner mitochondrial surface.
What is the function of carnitine acylcarnitine translocase?
It transports one molecule of carnitine out of mitochondria while transporting one acyl-carnitine molecule into mitochondria.
What is the function of carnitine acyltransferase II (CAT-II)?
It regenerates acyl-CoA and carnitine from acyl-carnitine inside mitochondria.
What is the immediate product of fatty acid beta oxidation?
Acetyl-CoA.
The first reaction of fatty acid beta-oxidation is catalyzed by fatty acyl CoA dehydrogenase. What is this enzyme's cofactor?
FAD (it is reduced to FADH2 and then relays the electrons to coenzyme Q).
The third reaction of fatty acid beta-oxidation is catalyzed by L-3-hydroxy fatty acyl CoA dehydrogenase. What is this enzyme's cofactor?
NAD+ (it is reduced to NADH).
Palmitic acid is a 16 carbon saturated fatty acid. Approximately how many ATP's are generated when palmitic acid is completely oxidized?
129.
Which two enzymes are involved in the oxidation of unsaturated fatty acids?
Enoyl isomerase and 2,4-dienoyl-CoA reductase.
When does alpha-oxidation of fatty acids occur?
When a branch point of a phytanic acid is encountered.
Which condition results from a genetic deficiency of alpha-oxidation enzymes?
Refsum's disease.
Generally, beta-oxidation of fatty acids always yields acetyl-CoA (two carbon molecule). What other product can be generated by alpha-oxidation of fatty acids?
Propionyl CoA (three carbon molecule).
The propionyl-CoA generated during alpha-oxidation is converted to what molecule?
It is carboxylated and rearranged to form succinyl-CoA, which is a TCA cycle intermediate.
Vitamin B12 deficiency is a cofactor for which enzyme involved in converting propionyl-CoA to succinyl-CoA?
Methylmalonyl-CoA mutase.
What is the most common cause of methylmalonic acidurea?
Vitamin B12 deficiency.
What is the purpose of peroxisomal fatty acid oxidation?
To break very long chain fatty acids into medium chain fatty acids.
List three differences between beta-oxidation and peroxisomal oxidation of fatty acids.
1. Carnitine is not required for transport of acyl-CoA from the cytoplasm into peroxisomes; 2. The first step of peroxisomal oxidation does not require FAD as a cofactor but oxygen instead and yields a peroxide instead of water; 3. Peroxisomal oxidation d
Which enzyme breaks down peroxides in peroxisomes?
Catalse.
What genertic disorder is caused by the absence of peroxisomes?
Zellweger syndrome. It is characterized by accumulation of very long chain fatty acids in various tissues.
What two ketone bodies are synthesized in the liver?
Acetoacetate and beta-hydroxybutyrate.
What reaction does HMG-CoA lyase catalyze?
It converts HMG-CoA into acetoacetate.
True or False. Acetoacetate and beta-hydroxybutyrate are interconverted by beta-hydroxybutyrate dehydrogenase, which is a reversible reaction that requires NADH/NAD+.
True.
What is the purpose of ketone bodies?
They provide energy for all tissues in the body (except the liver and erythrocytes) during low glucose conditions. They are particularly important for the brain.
What is the function of the extrahepatic enzyme 3-keto-acyl CoA transferase?
It metabolizes ketone bodies to provide energy in extrahepatic tissues. It converts acetoacetate and succinyl-CoA to acetoacetyl-CoA and succinate. Acetoacetyl-CoA is then cleaved into two acetyl-CoA molecules, which enter the TCA cycle to generate ATP.
What condition, when uncontrolled, is associated with ketoacidosis?
Diabetes mellitus.
What does the respiratory quotient measure?
How much carbon dioxide is released by a tissue per oxygen consumed during catabolic reaction (RQ = CO2/O2).
Cells in the intestine use 2-monoacylglycerol (2-MAG) as a backbone to synthesize fatty acids. What do hepatocytes use as a backbone for fatty acid synthesis?
Activated glycerol.
Nascent lipoproteins in the liver are associated with which lipoprotein?
ApoB-100.
What is the difference between ApoB-100 and ApoB-48?
Both are synthesized from the same gene but ApoB-48 is truncated because the DNA in the intestine is edited so that it contains a premature stop codon.
What is the difference between chylomicrons and very low density lipoprotein (VLDL)?
Chylomicrons are bigger and have a lower cholesterol esters to TAG ratio.
Where in the body and from what lipoprotein does very low density lipoprotein (VLDL) acquire ApoC-II?
In the blood after it is secreted by the liver, and it acquires ApoC-II from high density lipoprotein (HDL).
What is the approximate half-life of very low density lipoprotein (VLDL)?
2-4 hours.
What does very low density lipoprotein (VLDL) become when it loses ApoC-II?
Intermediate density lipoprotein (IDL).
Which apoproteins are present on mature very low density lipoproteins (VLDL)?
ApoB-100, ApoC-II and ApoE.
What is the function of ApoC-II?
It serves as a substrate for lipoprotein lipase.
What are the two fates of intermediate density lipoprotein (IDL)?
1) It can be depleted of triacylglycerols (TAGs) on the surface of hepatocytes by hepatic triacylglycerol lipase (HTGL), lose ApoE and become low density lipoprotein (LDL). 2) Alternatively, it can retain ApoE, bind to LDL receptors on liver cells with th
What is the major serum transporter of cholesterol?
Low density lipoprotein (LDL). Note that cholesterol is transported in the form of cholesterol esters.
Which lipoprotein(s) are present in low density lipoprotein (LDL)?
Only ApoB-100.
Where are the majority of low density lipoprotein (LDL) receptors found?
On hepatocytes. They may also be found on cells that require cholesterol such as those that produce steroid hormones like in the adrenal glands or sex organs.
What is the approximate half-life of low density lipoprotein (LDL)?
About 3 days.
What is the function of lipoprotein lipase (LPL)?
It hydrolyzes triacylglycerols (TAGs) on very low density lipoprotein (VLDL) into fatty acids.
Which form of cholesterol is a major risk factor for heart disease?
Low density lipoprotein (LDL).
Why is the presence of oxidized low density lipoprotein (LDL) in plasma injurious?
It stimulates endothelial cells to express adhesion molecules that attract monocytes. The monocytes then differentiate into mature monocytes, ingest oxidized LDL, become foam cells and die. This promotes smooth muscle growth and plaque formation in the va
True or False. Oxidized low density lipoproteins (LDL) are phagocytozed by mature macrophages.
False. Oxidized LDL binds to a scavenger receptor on the macrophages.
Where is high density lipoprotein (HDL) synthesized?
In the liver and intestine.
Which apolipoprotein(s) are present in high density liproteins (HDL)?
ApoA-I, ApoC-II and ApoE.
What is the main function of high density lipoprotein (HDL) with regards to cholesterol transport in blood?
HDL removes excess cholesterol when it encounters various cells throughout the body and transports it in the form of cholesterol esters to other tissues that need cholesterol. It also exchanges cholesterol esters for TAGs with chylomicrons, VLDL and IDL.
True or False. High density lipoprotein (HDL) is associated with heart disease.
False. HDL and heart disease are negatively correlated.
What is the function of ApoA-I?
It stimulates serum lecithin-cholesterol acyl transferase (LCAT).
What is the reaction catalyzed by serum lecithin-cholesterol acyl transferase (LCAT)?
LCAT esterifies cell membrane cholesterol to form cholesterol esters. Note that the fatty acid esterified to cholesterol does not come from a triacylglyerol. It comes from a membrane phospholipid.
What is the function of cholesterol ester transfer protein (CETP)?
It catalyzes the exchange of TAGs from chylomicrons, VLDL, or IDL with cholesterol esters on HDL.
What is the receptor for high density lipoprotein (HDL)?
It is thought to be scavenger receptor B1 (SR-BI).
What are two causes of hyperlipoproteinemias?
Excess production or decreased utilization of lipoproteins.
What is the main cause of hypobetalipoproteinemia?
Genetic defect in the ApoB gene. This is associated with deficiency of chylomicrons, VLDL and LDL.
HDL deficiency is associated with what condition?
Tangier disease.
What is the role of epinephrine and glucagon in fatty acid metabolism?
They are released when the body needs energy and activate a cAMP-dependent pathway that results in Protein kinase A (PKA) activation. PKA then inactivates acetyl-CoA carboxylase (blocks fatty acid synthesis) and stimulates hormone-sensitive lipase, HSL (c
Fatty acids can be carried on what blood protein?
Serum albumin.
What reaction is catalyzed by fatty acyl CoA synthetase?
Activation of a fatty acid by converting it to an acyl-CoA.
Where in the cell does activation of fatty acids occur?
In the ER or outer mitochondrial membrane.
Where in the cell does beta-oxidation of fatty acids occur?
In the mitochondrial matrix.
Acyl-CoA's cannot cross the mitochondrial membrane. In what form are they transported instead?
As acyl-carnitine.
What is the major regulatory step in fatty acid oxidation?
Conversion of acyl-CoA to acyl-carnitine by carnitine acyltransferase I (CAT-I).
What is the inhibitor of carnitine acyltransferase I (CAT-I)?
Malonyl-CoA.
Where in the cell does the carnitine acyltransferase I (CAT-I) reaction occur?
On the cytoplasmic side of the inner mitochondrial surface.
What is the function of carnitine acylcarnitine translocase?
It transports one molecule of carnitine out of mitochondria while transporting one acyl-carnitine molecule into mitochondria.
What is the function of carnitine acyltransferase II (CAT-II)?
It regenerates acyl-CoA and carnitine from acyl-carnitine inside mitochondria.
What is the immediate product of fatty acid beta oxidation?
Acetyl-CoA.
The first reaction of fatty acid beta-oxidation is catalyzed by fatty acyl CoA dehydrogenase. What is this enzyme's cofactor?
FAD (it is reduced to FADH2 and then relays the electrons to coenzyme Q).
The third reaction of fatty acid beta-oxidation is catalyzed by L-3-hydroxy fatty acyl CoA dehydrogenase. What is this enzyme's cofactor?
NAD+ (it is reduced to NADH).
Palmitic acid is a 16 carbon saturated fatty acid. Approximately how many ATP's are generated when palmitic acid is completely oxidized?
129
Which two enzymes are involved in the oxidation of unsaturated fatty acids?
Enoyl isomerase and 2,4-dienoyl-CoA reductase.
When does alpha-oxidation of fatty acids occur?
When a branch point of a phytanic acid is encountered.
Which condition results from a genetic deficiency of alpha-oxidation enzymes?
Refsum's disease.
Generally, beta-oxidation of fatty acids always yields acetyl-CoA (two carbon molecule). What other product can be generated by alpha-oxidation of fatty acids?
Propionyl CoA (three carbon molecule).
The propionyl-CoA generated during alpha-oxidation is converted to what molecule?
It is carboxylated and rearranged to form succinyl-CoA, which is a TCA cycle intermediate.
Vitamin B12 deficiency is a cofactor for which enzyme involved in converting propionyl-CoA to succinyl-CoA?
Methylmalonyl-CoA mutase.
What is the most common cause of methylmalonic acidurea?
Vitamin B12 deficiency.
What is the purpose of peroxisomal fatty acid oxidation?
To break very long chain fatty acids into medium chain fatty acids.
List three differences between beta-oxidation and peroxisomal oxidation of fatty acids.
1. Carnitine is not required for transport of acyl-CoA from the cytoplasm into peroxisomes; 2. The first step of peroxisomal oxidation does not require FAD as a cofactor but oxygen instead and yields a peroxide instead of water; 3. Peroxisomal oxidation d
Which enzyme breaks down peroxides in peroxisomes?
Catalse.
What genertic disorder is caused by the absence of peroxisomes?
Zellweger syndrome. It is characterized by accumulation of very long chain fatty acids in various tissues.
What two ketone bodies are synthesized in the liver?
Acetoacetate and beta-hydroxybutyrate.
What reaction does HMG-CoA lyase catalyze?
It converts HMG-CoA into acetoacetate.
True or False. Acetoacetate and beta-hydroxybutyrate are interconverted by beta-hydroxybutyrate dehydrogenase, which is a reversible reaction that requires NADH/NAD+.
True.
What is the purpose of ketone bodies?
They provide energy for all tissues in the body (except the liver and erythrocytes) during low glucose conditions. They are particularly important for the brain.
What is the function of the extrahepatic enzyme 3-keto-acyl CoA transferase?
It metabolizes ketone bodies to provide energy in extrahepatic tissues. It converts acetoacetate and succinyl-CoA to acetoacetyl-CoA and succinate. Acetoacetyl-CoA is then cleaved into two acetyl-CoA molecules, which enter the TCA cycle to generate ATP.
What condition, when uncontrolled, is associated with ketoacidosis?
Diabetes mellitus.
What does the respiratory quotient measure?
How much carbon dioxide is released by a tissue per oxygen consumed during catabolic reaction (RQ = CO2/O2).