Multiple Choice Question on Lipid and Lipoprotein Metabolism
1) A child was presented with diarrhea and failure to thrive. The clinical and biochemical investigation showed fat malabsorption, spinocerebellar degeneration, pigmented retinopathy, and acanthocytosis. develop. He had decreased night and color vision, followed by daytime visual acuity reductions. The blood chemistry profile showed extremely low plasma cholesterol and triglyceride levels with no detectable chylomicrons VLDL, LDL, or apoB.
The genetic analysis showed that the disease was inherited in an autosomal recessive manner.
Identify the probable cause from the following:
a) Mutation in the gene that codes for ApoB
b) Mutation in the gene that codes for MTP
c) Mutation in the gene that codes for ApoC-II
d) Mutation in the gene that codes for CEPT
a) Chylomicrons Identify the probable cause from the following:
a) Mutation in the gene that codes for ApoB
b) Mutation in the gene that codes for MTP
c) Mutation in the gene that codes for ApoC-II
d) Mutation in the gene that codes for CEPT
2) The biochemical analysis of plasma from a patient with pancreatitis showed hypertriglyceridemia with increased VLDL and chylomicrons. To further investigate, the patient was administered heparin intravenously and blood samples were collected to analyze the lipolytic activity in plasma. The test showed low LPL activity in post heparinized blood samples.
Identify the probable cause of reaction after an intravenous heparin injection increased VLDL and Chylomicrons
a) Deficiency of Apo B
b) Deficiency of Lipoprotein Lipase
c) Deficiency of LDL receptor
d) Deficiency of Apo A-I
3) The highest phospholipids content is found in …........................
b) VLDL
c) LDL
d) HDL
4) The class of lipoproteins that is protective against atherosclerosis is …...........................
a) Low-density of lipoproteins
b) Very low-density lipoproteins
c) High-density lipoproteins
d) Chylomicrons
5) Genetic deficiency of lipoprotein lipase cause hyperlipoproteinemia of the following type:
a) Type I
b) Type IIa
c) Type IIb
d) Type V
6) Activated lecithin cholesterol acyltransferase is essential for the conversion of ...
a) VLDL remnants into LDL
b) Nascent HDL into HDL
c) HDL2 into HDL3
d) HDL3 into HDL2
7) Zellweger’s syndrome is associated with the abnormality of
a) Nonessential fatty acid metabolism
b) Essential fatty acid metabolism
c) cholesterol metabolism
d) Lipoprotein metabolism
8) Tangier disease is a disorder of lipoprotein metabolism. The phenotype corresponds to
a) Low level of VLDL
b) Low level of LDL
c) Low level of IDL
d) Low level of HDL
9) Although ketogenesis occurs in hepatocytes it cannot utilize ketone bodies. It is due to a deficiency of which of the following enzyme?
a) Thiokinase
b) Thiophorase
c) Thiolase
d) Thiolyase
10) Fatty acid oxidation is regulated by malonyl CoA. The malonyl CoA inhibits
a) The entry of fatty acid into the cell
b) Activation of fatty acid to fatty acyl CoA
c) Shuttling of fatty acyl CoA to mitochondria
d) Dehydrogenation of fatty acyl CoA to enoyl CoA
a) The entry of fatty acid into the cell
b) Activation of fatty acid to fatty acyl CoA
c) Shuttling of fatty acyl CoA to mitochondria
d) Dehydrogenation of fatty acyl CoA to enoyl CoA
11) Familial Hypercholesterolemia is an autosomal dominant genetic disorder caused by a mutation of the gene that encodes for:
a) Apolipoprotein E
b) Apolipoprotein B
c) LDL receptor
d) VLDL receptor
12) Which of the following statement is true regarding familial hypercholesterolemia?
a) In heterozygotes, the serum cholesterol level range from 275 to 500 mg/dL
b) Plasma triglycerides are generally elevated >300 mg/dL
c) Serum LDL-cholesterol is within the normal range
d) All of the above
13) Familial Hypertriglyceridemia is characterized by
a) Increased plasma VLDL and triglycerides (200-500 mg/dL)
b) Normal or mildly increased cholesterol level (<250 mg/dL)
c) Reduced plasma HDL level
d) All of the above
14) Chylomicron is a type of lipoprotein that transports triglycerides from the intestine to peripheral tissues.
Which of the following is an integral apolipoprotein present in a chylomicron?
a) Apo B100
b) Apo B48
c) Apo CII
d) ApoE
15) Which of the following is an integral apolipoprotein present in VLDL, IDL, and LDL?
a) Apo B100
b) Apo B48
c) Apo CII
d) ApoE
16) The lipoprotein lipase is present in the endothelial surfaces of adipose tissues in the heart and it is required for hydrolysis and release of triglycerides from chylomicrons.
Which of the apolipoprotein that is present in chylomicron serves as the activator of an enzyme lipoprotein lipase?
a) Apo B100
b) Apo B48
c) Apo CII
d) ApoE
17) Chylomicron remnants are rapidly taken by the liver in a process that requires
a) Apo B100
b) Apo B48
c) Apo CII
d) ApoE
18) HDL is a type of lipoprotein that is important for acquiring cholesterol from VLDL and chylomicrons.
Which of the following proteins are important for HDL function?
a) Apo A-I
b) Lecithin-Cholesterol Acyltransferase (LCAT)
c) Cholesteryl Ester Transport Protein
d) All of the Above
19) The clearance of LDL cholesterols in hepatocytes requires:
a) LDL receptor
b) Apo CII receptor
c) Scavenger receptor BI
d) None of the above
20) The HDL is taken up by the hepatocytes via.................................
a) LDL receptor
b) Apo CII receptor
c) Scavenger receptor BI
d) None of the above
Answers to Multiple Choice Question:
1- b) Mutation in the gene that codes for MTP
The blood chemistry profile you're describing—extremely low plasma cholesterol and triglyceride levels with no detectable chylomicrons, VLDL, LDL, or apoB—is indicative of a severe lipid transport disorder, specifically abetalipoproteinemia. This condition is caused by mutations in the gene that codes for Microsomal Triglyceride Transfer Protein (MTP).
The absence of chylomicrons and VLDL indicates that the body's ability to transport dietary fats and endogenous lipids is severely compromised. This can lead to the symptoms and complications mentioned previously, such as steatorrhea, malnutrition, neurological issues, liver problems, and potential cardiovascular risks.
The lack of LDL and apoB is significant because these lipoproteins are involved in transporting cholesterol to various tissues in the body.
2- b) Deficiency of Lipoprotein Lipase
If there's an increase in VLDL (very low-density lipoprotein) and chylomicrons after an intravenous heparin injection, it suggests an abnormal lipid response that could be due to a lipid metabolism disorder. One possible cause of this reaction is Lipoprotein Lipase (LPL) deficiency or dysfunction.
Lipoprotein Lipase (LPL) is an enzyme that plays a crucial role in breaking down triglycerides present in VLDL and chylomicrons, releasing fatty acids for energy utilization. If there is a deficiency or dysfunction of LPL, triglycerides are not efficiently metabolized, leading to an accumulation of VLDL and chylomicrons in the bloodstream. This can result in increased levels of these lipoproteins.
The phospholipid content in lipoproteins varies depending on the type of lipoprotein. Here is a general overview of the phospholipid proportion in different lipoproteins:
High-Density Lipoproteins (HDL): HDLs are involved in reverse cholesterol transport, removing excess cholesterol from peripheral tissues and transporting it to the liver for excretion. HDLs have the highest proportion of phospholipids relative to their lipid components, making up a significant portion of their surface monolayer.
Chylomicrons: Chylomicrons are the largest lipoproteins and transport dietary lipids, primarily triglycerides, from the intestines to various tissues. They have a relatively low proportion of phospholipids compared to their triglyceride content.
Very Low-Density Lipoproteins (VLDL): VLDLs transport endogenous triglycerides synthesized by the liver to peripheral tissues. They contain more phospholipids than chylomicrons but still have a higher proportion of triglycerides and cholesterol esters.
Low-Density Lipoproteins (LDL): LDLs are often referred to as "bad cholesterol" because they carry cholesterol to peripheral tissues. LDLs contain a lower proportion of phospholipids compared to VLDLs and have a higher proportion of cholesterol esters.
4-c) High-density lipoproteins
High-Density Lipoproteins (HDL) are the class of lipoproteins that are often considered protective against atherosclerosis. Atherosclerosis is a complex cardiovascular disease characterized by the buildup of plaque within arteries, leading to narrowing and hardening of the arteries. This condition can contribute to various cardiovascular issues, including heart attacks and strokes.
5- b) Type IIa
6-d) HDL3 into HDL2
Activated lecithin cholesterol acyltransferase (LCAT) is essential for the conversion of HDL3 (High-Density Lipoprotein 3) to HDL2 (High-Density Lipoprotein 2). This conversion involves the esterification of free cholesterol within HDL particles, leading to changes in particle size and lipid composition that are characteristic of HDL2.
7-b) Essential fatty acid metabolism
Zellweger syndrome, also known as Zellweger spectrum disorder, is a rare genetic disorder that is associated with the abnormality of peroxisomes. Peroxisomes are cellular organelles involved in various metabolic processes, including lipid metabolism, the breakdown of fatty acids, and the detoxification of harmful substances.
In individuals with Zellweger syndrome, peroxisomes are either absent or severely dysfunctional due to a mutation in one of the genes responsible for peroxisome biogenesis. This leads to a range of health issues and developmental abnormalities, primarily affecting the brain, liver, and other organs.
8-d) Low level of HDL
Tangier disease is indeed a rare disorder of lipoprotein metabolism that is associated with abnormal lipid accumulation. The phenotype (observable characteristics and symptoms) of Tangier disease corresponds to the deposition of cholesterol esters within various tissues, leading to the enlargement of certain organs and the development of characteristic physical features.
Individuals with Tangier disease often exhibit very low levels of high-density lipoprotein (HDL) cholesterol. This is due to impaired cellular cholesterol efflux, resulting in decreased HDL levels.
9-b) Thiophorase
10-c) Shuttling of fatty acyl CoA to mitochondria
Malonyl-CoA inhibits fatty acid oxidation by inhibiting the enzyme Carnitine Palmitoyltransferase I (CPT-I). CPT-I is a key regulatory enzyme involved in the transport of long-chain fatty acids into the mitochondria, where fatty acid oxidation takes place. The inhibition of CPT-I by malonyl-CoA helps regulate the balance between fatty acid synthesis and fatty acid oxidation.
11-c) LDL receptor
Mutations in the gene responsible for the LDL receptor (LDLR) are a primary cause of FH. These mutations often lead to a malfunctioning or less efficient LDL receptor, impairing its ability to bind and internalize LDL particles effectively. Consequently, there is diminished clearance of LDL cholesterol from the bloodstream, resulting in a surplus accumulation that elevates LDL cholesterol levels and raises the risk of atherosclerosis and cardiovascular diseases.
12- a) In heterozygotes, the serum cholesterol level range from 275 to 500 mg/dL
The correct statement is that in heterozygotes (individuals with one mutated allele for FH), the serum cholesterol level typically ranges from 275 to 500 mg/dL. This is a key diagnostic feature of the disorder.
13)-Increased plasma VLDL and triglycerides (200-500 mg/dL)
Familial Hypertriglyceridemia is a genetic disorder characterized by elevated levels of triglycerides in the blood. Triglycerides are a type of lipid (fat) that plays a role in energy storage.
14)-b) Apo B48
Apolipoprotein B-48 (ApoB-48) is a protein associated with chylomicrons, which are large lipoprotein particles primarily responsible for transporting dietary triglycerides and other lipids from the intestines to various tissues throughout the body. Chylomicrons are formed in the intestine after the digestion of dietary fats.
ApoB-48 is synthesized in the intestines from the same gene that produces ApoB-100, a protein found in very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL). The "48" in ApoB-48's name refers to its molecular weight of approximately 48 kDa.
15)-a) Apo B100
Apolipoprotein B-100 (ApoB-100) is a protein associated with several lipoprotein particles, including very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL). ApoB-100 plays a crucial role in lipid metabolism and is involved in the transport of cholesterol and triglycerides throughout the body.
Key points about ApoB-100 include:
VLDL: ApoB-100 is synthesized in the liver and is a major component of VLDL particles. VLDL particles transport triglycerides synthesized in the liver to various tissues for energy storage.
IDL: When VLDL particles lose triglycerides through the action of lipoprotein lipase (LPL) in the bloodstream, they become IDL particles. ApoB-100 is also present on IDL particles.
LDL: Further removal of triglycerides from IDL particles results in the formation of LDL particles, commonly known as "bad cholesterol." LDL particles primarily transport cholesterol to cells throughout the body.
Binding and Uptake: LDL particles interact with LDL receptors on the surface of cells. ApoB-100 binds to these receptors, facilitating the uptake of LDL particles into cells. This process is essential for delivering cholesterol to cells for membrane synthesis, hormone production, and other essential functions.
16- c) ApoCII
Apolipoprotein C-II (ApoC-II) is the apolipoprotein present in chylomicrons that serves as the activator of the enzyme lipoprotein lipase (LPL).
Lipoprotein lipase is an enzyme that plays a central role in lipid metabolism by hydrolyzing triglycerides present in circulating lipoproteins, such as chylomicrons and very low-density lipoproteins (VLDL). ApoC-II, when present on the surface of chylomicrons, interacts with lipoprotein lipase and activates its enzymatic activity. This activation allows lipoprotein lipase to hydrolyze triglycerides into fatty acids and glycerol, which can then be taken up by various tissues for energy production or storage.
17-d) Apo E
Chylomicron remnants are rapidly taken up by the liver through a process that requires d) ApoE.
Formation of Chylomicron Remnants: After chylomicrons release their triglycerides through the action of lipoprotein lipase, they become chylomicron remnants. These remnants are smaller lipoprotein particles that still contain various apolipoproteins on their surface, including ApoB-48.
Role of ApoE: ApoE is another apolipoprotein that is present on the surface of chylomicron remnants. It plays a key role in the recognition and clearance of these remnants by specific receptors on the surface of liver cells (hepatocytes).
Liver Uptake: ApoE acts as a ligand that interacts with specific receptors on hepatocytes, including the LDL receptor-related protein (LRP) and the remnant receptor. This interaction triggers a process known as receptor-mediated endocytosis. The hepatocytes then internalize the chylomicron remnants along with the ApoE ligand via endocytosis.
Clearance and Recycling: Once internalized by hepatocytes, the chylomicron remnants are broken down, and their components (including cholesterol and other lipids) are recycled or processed by the liver for further use or excretion.
18-d) All of the Above
All three of the mentioned proteins are important for HDL (High-Density Lipoprotein) function:
a) Apolipoprotein A-I (Apo A-I): This is the main protein component of HDL. It plays a crucial role in the initial formation of HDL particles, as well as in the reverse cholesterol transport process, where excess cholesterol is removed from peripheral tissues and transported to the liver for excretion.
b) Lecithin-Cholesterol Acyltransferase (LCAT): LCAT is an enzyme associated with HDL that catalyzes the esterification of free cholesterol within HDL particles. This process is essential for the maturation and enlargement of HDL particles, enabling them to carry more cholesterol.
c) Cholesteryl Ester Transfer Protein (CETP): CETP facilitates the transfer of cholesteryl esters from HDL to other lipoproteins, such as LDL (Low-Density Lipoprotein) and VLDL (Very-Low-Density Lipoprotein). This protein is involved in the exchange of cholesterol esters and triglycerides between different lipoprotein particles.
19-a) LDL receptor
The clearance of LDL (Low-Density Lipoprotein) cholesterol in hepatocytes primarily requires the presence of LDL receptors. These receptors bind to LDL particles, allowing the hepatocytes to take up LDL cholesterol from the bloodstream. This process helps regulate cholesterol levels in the body and prevents the buildup of excess LDL cholesterol in the arteries, which is associated with cardiovascular diseases. Apo CII receptor and Scavenger receptor BI are not directly involved in the clearance of LDL cholesterol in hepatocytes.
20-c) Scavenger receptor BI
HDL (High-Density Lipoprotein) is taken up by hepatocytes primarily via the Scavenger receptor BI (SR-BI). This receptor facilitates the selective uptake of cholesterol esters from HDL particles into hepatocytes. This process contributes to the reverse cholesterol transport pathway, where excess cholesterol from peripheral tissues is transported to the liver for excretion.
