Lipid Metabolism Practice Questions

Q: Which enzyme is deficient in Refsum disease?

Phytanoyl-CoA a-hydroxylase. **Explanation:** **Refsum Disease** is a rare autosomal recessive peroxisomal disorder characterized by the inability to degrade **phytanic acid**, a 20-carbon branched-chain fatty acid derived from chlorophyll in the diet. 1. **Why Option B is Correct:** Phytanic acid has a methyl group at the beta-carbon, which blocks normal $\beta$-oxidation. To bypass this, the body uses **$\alpha$-oxidation** to remove the first carbon atom as $CO_2$. The key enzyme for this process is **Phytanoyl-CoA $\alpha$-hydroxylase (PhyH)**. In Refsum disease, a deficiency of this enzyme leads to the toxic accumulation of phytanic acid in tissues and plasma, particularly affecting the nervous system and retina. 2. **Why Other Options are Incorrect:** * **A. Sphingomyelinase:** Deficient in **Niemann-Pick disease**, leading to sphingomyelin accumulation. * **C. Alpha-galactosidase A:** Deficient in **Fabry disease**, an X-linked lysosomal storage disorder. * **D. N-acetylglucosaminidase:** Deficient in **Sanfilippo syndrome Type B** (a Mucopolysaccharidosis). **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Retinitis pigmentosa, peripheral neuropathy, and cerebellar ataxia. Other features include sensorineural deafness and ichthyosis (scaly skin). * **Diagnosis:** Elevated serum levels of phytanic acid. * **Management:** Dietary restriction of chlorophyll-containing foods (e.g., green leafy vegetables, dairy, and ruminant fats). * **Zellweger Syndrome vs. Refsum:** While both involve peroxisomes, Zellweger is a defect in peroxisome *biogenesis*, whereas Refsum is a specific enzyme defect in $\alpha$-oxidation.

Q: What is the main component of surfactant?

Dipalmitoyl phosphatidylcholine. **Explanation:** **1. Why Dipalmitoyl phosphatidylcholine (DPPC) is correct:** Lung surfactant is a complex mixture of lipids and proteins, but it is composed of approximately **90% lipids**. The most abundant and functionally significant lipid (accounting for ~50-60% of total surfactant) is **Dipalmitoyl phosphatidylcholine (DPPC)**, also known as **Lecithin**. * **Mechanism:** DPPC is an amphipathic molecule. Its hydrophobic fatty acid tails point toward the air, while the hydrophilic head points toward the alveolar water layer. This orientation significantly **reduces surface tension** at the air-liquid interface, preventing alveolar collapse (atelectasis) during expiration. **2. Why the other options are incorrect:** * **Phosphatidylinositol:** While present in surfactant, it is a minor component (approx. 5-10%) and does not play the primary role in reducing surface tension. * **Dipalmitoyl cephalin (Phosphatidylethanolamine):** Cephalin is a major component of cell membranes (especially nervous tissue) but is not the primary constituent of surfactant. * **Dipalmitoyl serine:** Phosphatidylserine is involved in cell signaling and apoptosis (flipping to the outer membrane leaflet), but it is not a major component of lung surfactant. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **L/S Ratio:** Fetal lung maturity is assessed by the **Lecithin/Sphingomyelin ratio** in amniotic fluid. A ratio **>2.0** indicates mature lungs. * **Type II Pneumocytes:** Surfactant is synthesized and secreted by Type II alveolar cells and stored in **Lamellar bodies**. * **NRDS:** Deficiency of surfactant in premature infants leads to **Neonatal Respiratory Distress Syndrome (Hyaline Membrane Disease)**. * **Glucocorticoids:** These are administered to mothers in preterm labor to stimulate surfactant production by inducing enzymes like *cholinephosphotransferase*.

Q: HMG-CoA Reductase is associated with which of the following conditions?

Familial Hypercholesterolemia. ### Explanation **Correct Option: B. Familial Hypercholesterolemia** HMG-CoA Reductase is the **rate-limiting enzyme** in the de novo synthesis of cholesterol, converting HMG-CoA to Mevalonate. In **Familial Hypercholesterolemia (FH)**, there is a primary defect in LDL receptors (Type IIa hyperlipidemia). This leads to decreased cellular uptake of LDL-cholesterol. Under normal physiological conditions, intracellular cholesterol exerts **negative feedback inhibition** on HMG-CoA Reductase. In FH, because cholesterol cannot enter the cell effectively, this feedback mechanism fails, leading to the constitutive over-activation of HMG-CoA Reductase and excessive endogenous cholesterol production. Statins, the mainstay of treatment, work by competitively inhibiting this specific enzyme. **Analysis of Incorrect Options:** * **A. Type 2 Diabetes:** Primarily associated with insulin resistance and dysregulation of enzymes like Glucokinase or PEPCK, rather than a primary defect involving HMG-CoA Reductase. * **C. Gaucher's disease:** This is a Lysosomal Storage Disorder caused by a deficiency of **Glucocerebrosidase** (Acid β-glucosidase), leading to the accumulation of glucosylceramide. * **D. Abetalipoproteinemia:** Caused by a mutation in the **Microsomal Triglyceride Transfer Protein (MTP)**, resulting in an inability to assemble or secrete ApoB-containing lipoproteins (VLDL, LDL, and Chylomicrons). **High-Yield Clinical Pearls for NEET-PG:** * **Location:** HMG-CoA Reductase is located in the **Endoplasmic Reticulum (ER)** membrane. * **Regulation:** It is inhibited by **Glucagon** (via phosphorylation) and activated by **Insulin** (via dephosphorylation). * **Statins:** These are structural analogs of HMG-CoA and act as reversible competitive inhibitors. * **SREBP Path:** Low intracellular cholesterol triggers SREBP (Sterol Regulatory Element Binding Protein) to increase the transcription of the HMG-CoA Reductase gene.

Q: Saturated fatty acids containing up to 16 carbon atoms are assembled in which cellular location?

Cytoplasm. **Explanation:** The correct answer is **Cytoplasm** because the **De novo synthesis of fatty acids** (specifically Palmitate, a 16-carbon saturated fatty acid) occurs primarily in the cytosol. This process is catalyzed by the **Fatty Acid Synthase (FAS) multienzyme complex**. The primary substrate is Acetyl-CoA, which is transported from the mitochondria to the cytoplasm via the **Citrate-Malate shuttle**. The rate-limiting step of this pathway is the conversion of Acetyl-CoA to Malonyl-CoA by the enzyme Acetyl-CoA Carboxylase (ACC). **Analysis of Incorrect Options:** * **Mitochondria:** While the mitochondria are the primary site for **$\beta$-oxidation** (breakdown) of fatty acids and the synthesis of Acetyl-CoA, they are not the site for assembly of fatty acids up to 16 carbons. A separate system for fatty acid elongation exists here, but it is minor. * **Smooth Endoplasmic Reticulum (SER):** The SER is the site for **chain elongation** (beyond 16 carbons) and **desaturation** (adding double bonds) of pre-existing fatty acids. It is also the primary site for triacylglycerol and phospholipid synthesis. * **Rough Endoplasmic Reticulum (RER):** This organelle is primarily involved in protein synthesis and post-translational modifications, not lipid assembly. **High-Yield Clinical Pearls for NEET-PG:** * **Rate-limiting enzyme:** Acetyl-CoA Carboxylase (requires **Biotin** as a cofactor). * **Reducing equivalent:** **NADPH** is the essential electron donor for fatty acid synthesis, primarily supplied by the Hexose Monophosphate (HMP) Shunt. * **Key Shuttle:** The **Citrate shuttle** moves Acetyl-CoA out of the mitochondria; Citrate acts as an allosteric activator of Acetyl-CoA Carboxylase. * **Inhibitor:** Palmitoyl-CoA (the end product) provides feedback inhibition.

Q: Triglycerides are transported from the liver to the tissues by which of the following lipoproteins?

VLDL (Very-low-density lipoprotein). ### Explanation **Correct Answer: C. VLDL (Very-low-density lipoprotein)** **Mechanism:** The liver synthesizes **endogenous triglycerides** from excess carbohydrates and free fatty acids. Because lipids are hydrophobic, they must be packaged into lipoproteins for transport in the aqueous environment of the plasma. **VLDL** is the primary vehicle for transporting these endogenously synthesized triglycerides from the **liver to peripheral tissues** (muscle and adipose tissue). Once in the circulation, VLDL undergoes hydrolysis by the enzyme *Lipoprotein Lipase (LPL)*, releasing free fatty acids for energy or storage. **Analysis of Incorrect Options:** * **A. HDL:** Known as "Good Cholesterol," its primary role is **Reverse Cholesterol Transport**—carrying excess cholesterol from peripheral tissues back to the liver. * **B. LDL:** Formed from VLDL (via IDL), LDL is the primary carrier of **cholesterol** (not triglycerides) to peripheral tissues. * **D. Chylomicrons:** These transport **exogenous (dietary) triglycerides** from the intestines to the peripheral tissues. They do not originate in the liver. **High-Yield NEET-PG Pearls:** * **Apolipoprotein Marker:** **Apo B-100** is the characteristic structural protein for VLDL, IDL, and LDL. (Contrast: **Apo B-48** is for Chylomicrons). * **Rate-limiting step:** The assembly of VLDL requires the **Microsomal Triglyceride Transfer Protein (MTP)**. A deficiency in MTP leads to *Abetalipoproteinemia*. * **Clinical Correlation:** Type IV Hyperlipoproteinemia is characterized by isolated elevation of VLDL due to overproduction or decreased clearance. * **Fatty Liver:** If the liver cannot synthesize VLDL (e.g., due to protein deficiency or choline deficiency), triglycerides accumulate in hepatocytes, leading to hepatic steatosis.

Q: In the structure of cholesterol, where is the double bond located?

Ring B. **Explanation:** Cholesterol is a 27-carbon steroid molecule characterized by the **cyclopentanoperhydrophenanthrene (CPPP)** nucleus. This nucleus consists of four fused rings: three cyclohexane rings (A, B, and C) and one cyclopentane ring (D). **Why Option C is correct:** The chemical structure of cholesterol features a single double bond located between **Carbon-5 and Carbon-6**. These carbons are part of **Ring B**. This unsaturation is a defining structural feature of cholesterol and is essential for its chemical reactivity and its role as a precursor for steroid hormones. **Analysis of Incorrect Options:** * **Ring A:** Contains the hydroxyl (-OH) group at the **C3 position**, which makes cholesterol an alcohol (sterol), but it does not contain a double bond. * **Ring C:** This is a saturated six-membered ring located between Ring B and Ring D; it contains no double bonds or functional groups in the native cholesterol molecule. * **Ring D:** This is the five-membered ring (cyclopentane). While it does not have a double bond, it is the site of attachment for the **8-carbon hydrocarbon side chain** at the **C17 position**. **High-Yield NEET-PG Clinical Pearls:** * **Precursor Role:** Cholesterol is the parent compound for bile acids, Vitamin D, and all steroid hormones (progesterone, cortisol, aldosterone, testosterone, and estrogen). * **Rate-Limiting Step:** The synthesis of cholesterol occurs in the cytosol/ER, regulated by the enzyme **HMG-CoA Reductase** (inhibited by Statins). * **Amphipathic Nature:** The -OH group on Ring A is polar, while the rest of the molecule is non-polar, allowing it to modulate cell membrane fluidity. * **Identification:** The presence of the double bond in Ring B allows for the **Libermann-Burchard reaction**, where cholesterol turns emerald green in the presence of acetic anhydride and concentrated sulfuric acid.

Q: Acetyl CoA carboxylase is activated by which molecule?

Citrate. **Explanation:** **Acetyl CoA Carboxylase (ACC)** is the **rate-limiting enzyme** in de novo fatty acid synthesis (lipogenesis). It catalyzes the conversion of Acetyl CoA to Malonyl CoA. **1. Why Citrate is Correct:** Citrate acts as a **feed-forward allosteric activator**. Fatty acid synthesis occurs in the cytoplasm, but Acetyl CoA is produced in the mitochondria. Since Acetyl CoA cannot cross the mitochondrial membrane, it condenses with oxaloacetate to form Citrate, which is then shuttled into the cytoplasm. High levels of cytoplasmic Citrate signal an energy surplus, triggering the **polymerization** of inactive ACC dimers into active long filaments, thereby stimulating lipogenesis. **2. Analysis of Incorrect Options:** * **Malonyl CoA (A):** This is the immediate product of the ACC reaction. It does not activate ACC; rather, it serves as a potent inhibitor of *Carnitine Palmitoyltransferase-I (CPT-1)*, preventing the entry of fatty acids into mitochondria for beta-oxidation. * **Palmitoyl CoA (C):** This is the end-product of fatty acid synthesis. It acts as a **feedback allosteric inhibitor**, causing the active ACC filaments to dissociate back into inactive dimers. * **Acetoacetate (D):** This is a ketone body. While it is related to lipid metabolism, it does not play a direct regulatory role in the activation of ACC. **High-Yield Clinical Pearls for NEET-PG:** * **Hormonal Regulation:** ACC is activated by **Insulin** (via dephosphorylation) and inhibited by **Glucagon/Epinephrine** (via phosphorylation by AMPK). * **Cofactor Requirement:** ACC requires **Biotin (Vitamin B7)**, ATP, and $CO_2$ (ABC carboxylase rule). * **Location:** Occurs in the "Liver, Lactating mammary gland, and Adipose tissue" (Mnemonic: **LLA**).

Q: All of the following sphingolipidoses have an autosomal recessive inheritance pattern except?

Fabry's disease. **Explanation:** The correct answer is **Fabry’s disease**. In medical genetics and biochemistry, most enzyme deficiencies (including most lysosomal storage disorders) follow an **Autosomal Recessive (AR)** inheritance pattern. However, Fabry’s disease and Hunter syndrome (a mucopolysaccharidosis) are the two major exceptions that follow an **X-linked Recessive (XLR)** pattern. **1. Why Fabry’s disease is the correct answer:** Fabry’s disease is caused by a deficiency of the enzyme **$\alpha$-galactosidase A**, leading to the accumulation of **ceramide trihexoside**. Because the gene encoding this enzyme is located on the X chromosome, it is inherited in an X-linked recessive manner, primarily affecting males. **2. Why the other options are incorrect:** * **Niemann-Pick disease:** Caused by sphingomyelinase deficiency; it follows a classic AR pattern. * **Tay-Sachs disease:** Caused by Hexosaminidase A deficiency; it is a classic AR disorder, notably prevalent in the Ashkenazi Jewish population. * **Gaucher’s disease:** The most common lysosomal storage disorder, caused by $\beta$-glucocerebrosidase deficiency; it follows an AR pattern. **NEET-PG High-Yield Pearls:** * **Mnemonic for X-linked Recessive Lysosomal Disorders:** "The **Hunter** aimed for the **Fabry** (Fabric)" $\rightarrow$ **Hunter Syndrome** and **Fabry’s Disease** are XLR. * **Clinical Triad of Fabry’s:** Episodic peripheral neuropathy (burning pain), angiokeratomas, and hypohidrosis. Late-stage complications include renal failure and cardiovascular disease. * **Biopsy Finding:** "Maltese crosses" (lipid globules) in urine sediment or "Zebra bodies" on electron microscopy are characteristic of Fabry's.

Q: Plasmalogens belong to which group of compounds?

Phospholipid. **Explanation:** **1. Why Phospholipid is Correct:** Plasmalogens are a unique class of **glycerophospholipids**. While most phospholipids (like lecithin) contain fatty acids attached via ester bonds at both the C1 and C2 positions of glycerol, plasmalogens are characterized by an **ether linkage** at the C1 position. Specifically, they contain an unsaturated alkyl group joined to glycerol by a vinyl ether bond. Because they possess a phosphate group and a glycerol backbone, they are structurally classified as phospholipids. The most common example is **ethanolamine plasmalogen**, found abundantly in myelin and cardiac muscle. **2. Why Incorrect Options are Wrong:** * **Sphingolipids (B):** These are lipids built on a **sphingosine** backbone (an amino alcohol) rather than glycerol. Examples include sphingomyelin and cerebrosides. Plasmalogens have a glycerol backbone, excluding them from this group. * **Aminosugars (C):** These are carbohydrates where a hydroxyl group is replaced by an amino group (e.g., Glucosamine). They are components of glycosaminoglycans (GAGs) and have no structural relation to the lipid nature of plasmalogens. **3. NEET-PG High-Yield Clinical Pearls:** * **Zellweger Syndrome:** This is a peroxisomal biogenesis disorder. Since the initial steps of plasmalogen synthesis occur in **peroxisomes**, patients with Zellweger syndrome show a marked deficiency in plasmalogens. * **PAF (Platelet Activating Factor):** Structurally related to plasmalogens, PAF is an ether lipid (alkyl-ether) but lacks the double bond (vinyl) characteristic of true plasmalogens. * **Function:** Plasmalogens act as potent antioxidants and protect effector cells from oxidative stress.

Question 1

Which enzyme is deficient in Refsum disease?

Accepted Answer

Phytanoyl-CoA a-hydroxylase

Answer

Sphingomyelinase

Answer

Alpha galactosidase-A

Answer

N-acetylglucosaminidase

Question 2

What is the main component of surfactant?

Accepted Answer

Dipalmitoyl phosphatidylcholine

Answer

Phosphatidylinositol

Answer

Dipalmitoyl cephalin

Answer

Dipalmitoyl serine

Question 3

HMG-CoA Reductase is associated with which of the following conditions?

Accepted Answer

Familial Hypercholesterolemia

Answer

Type 2 Diabetes

Answer

Gaucher's disease

Answer

Abetalipoproteinemia

Question 4

Saturated fatty acids containing up to 16 carbon atoms are assembled in which cellular location?

Accepted Answer

Cytoplasm

Answer

Mitochondria

Answer

Rough endoplasmic reticulum

Answer

Smooth endoplasmic reticulum

Question 5

Triglycerides are transported from the liver to the tissues by which of the following lipoproteins?

Accepted Answer

VLDL (Very-low-density lipoprotein)

Answer

HDL (High-density lipoprotein)

Answer

LDL (Low-density lipoprotein)

Answer

Chylomicrons

Question 6

In the structure of cholesterol, where is the double bond located?

Accepted Answer

Ring B

Answer

Ring D

Answer

Ring C

Answer

Ring A

Question 7

Acetyl CoA carboxylase is activated by which molecule?

Accepted Answer

Citrate

Answer

Malonyl CoA

Answer

Palmitoyl CoA

Answer

Acetoacetate

Question 8

All of the following sphingolipidoses have an autosomal recessive inheritance pattern except?

Accepted Answer

Fabry's disease

Answer

Niemann-Pick disease

Answer

Tay-Sachs disease

Answer

Gaucher's disease

Question 9

Multiple sclerosis is characterized by a loss of which lipids?

Accepted Answer

Phospholipids and sphingolipids

Answer

Phospholipids and ceramide

Answer

Sphingolipids and ceramide

Answer

Sphingolipids and gangliosides

Question 10

Plasmalogens belong to which group of compounds?

Accepted Answer

Phospholipid

Answer

Sphingolipids

Answer

Aminosugars

Answer

None of the above

Lipid Metabolism — MCQs

Lipid Metabolism — MCQs

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