Lipid Metabolism Practice Questions

Q: Tay-Sachs disease is due to a deficiency of which enzyme?

Hexosaminidase A. ***Hexosaminidase A*** - **Tay-Sachs disease** is caused by a genetic deficiency in the lysosomal enzyme **hexosaminidase A (HexA)**. - This deficiency leads to the accumulation of **GM2 ganglioside** in neuronal cells, particularly in the brain, causing progressive neurodegeneration. *Hexosaminidase B* - A deficiency in **hexosaminidase B** is associated with **Sandhoff disease**, a lysosomal storage disorder similar to Tay-Sachs but typically more severe. - While HexA is composed of alpha and beta subunits, a deficiency specifically in the beta subunit is characteristic of Sandhoff disease. *α-galactosidase* - A deficiency in **α-galactosidase** is responsible for **Fabry disease**, an X-linked lysosomal storage disorder. - It leads to the accumulation of **globotriaosylceramide (Gb3)**, primarily affecting the kidneys, heart, and nervous system, and does not present with the neurological symptoms of Tay-Sachs. *Sphingomyelinase* - A deficiency in **sphingomyelinase** causes **Niemann-Pick disease (Type A and B)**, another lysosomal storage disorder. - This leads to the accumulation of **sphingomyelin** in various organs, resulting in hepatosplenomegaly, neurodegeneration (in Type A), and lung disease, distinct from Tay-Sachs.

Q: Congenital 17-hydroxylase deficiency leads to hypertension due to the accumulation of?

Deoxycorticosterone. ***Deoxycorticosterone*** - **17-hydroxylase deficiency** blocks the conversion of **pregnenolone** to **17-hydroxypregnenolone** and **progesterone** to **17-hydroxyprogesterone**, leading to an accumulation of precursors in the **mineralocorticoid pathway**. - This accumulation results in elevated levels of **deoxycorticosterone (DOC)**, a potent mineralocorticoid, which causes **sodium retention** and **hypertension**. *Cortisol* - **17-hydroxylase deficiency** prevents the synthesis of **cortisol**, as **17-hydroxyprogesterone** is a necessary intermediate. - Therefore, **cortisol levels are low**, not elevated, in this condition. *17-hydroxy pregnenediol* - **17-hydroxylase deficiency** directly impairs the formation of **17-hydroxypregnenolone** from **pregnenolone**. - Consequently, the levels of **17-hydroxypregnenolone** are very low or undetectable, not accumulated, in this disorder. *17-hydroxy progesterone* - The enzyme **17-hydroxylase** is required for the conversion of **progesterone** to **17-hydroxyprogesterone**. - Thus, the deficiency of this enzyme leads to **decreased levels of 17-hydroxyprogesterone**, rather than its accumulation.

Q: The fatty acid present in breast milk which is important for growth and CNS development is:

Docosahexaenoic acid. ***Docosahexaenoic acid*** - **Docosahexaenoic acid (DHA)** is a crucial **omega-3 fatty acid** abundantly found in breast milk. - It plays a vital role in the **development of the brain** and **retina**, particularly during infancy. *Palmitic acid* - **Palmitic acid** is a **saturated fatty acid** and a major component of fats in both plants and animals, including breast milk. - While it serves as an **energy source**, it is not primarily recognized for its specific role in CNS development like DHA. *Linolenic acid* - **Alpha-linolenic acid (ALA)** is an **omega-3 essential fatty acid** that is a precursor to DHA and EPA, meaning the body can convert it into these longer-chain fatty acids. - While important as a precursor, **ALA itself is not the direct fatty acid** primarily responsible for brain and CNS development in the same way DHA is. *Linoleic acid* - **Linoleic acid** is an **omega-6 essential fatty acid**, meaning the body cannot produce it and it must be obtained from the diet. - It is important for overall growth and development, but it is not specifically highlighted for its direct role in **CNS development** in the same way DHA is for breast milk.

Q: Dietary cholesterol is transported from the intestine to the liver by:

Apo-B. ***Apo-B*** - **Apolipoprotein B-48** (Apo-B48) is the key structural protein of **chylomicrons**, which are large lipoprotein particles formed in intestinal enterocytes. - Chylomicrons are responsible for transporting **dietary triglycerides** and **cholesterol** from the intestine via the lymphatic system into the bloodstream and ultimately to the liver. - Apo-B48 is essential for chylomicron assembly and secretion from the intestine. *Apo-A* - **Apolipoprotein A-I** (ApoA-I) is the primary apolipoprotein of **high-density lipoprotein (HDL)**. - HDL is mainly involved in **reverse cholesterol transport**, moving cholesterol from peripheral tissues back to the liver. *Apo-C* - **Apolipoprotein C-II** (ApoC-II) is an activator of **lipoprotein lipase (LPL)**, which metabolizes triglycerides in chylomicrons and VLDL. - **Apolipoprotein C-III** (ApoC-III) inhibits LPL activity and hepatic uptake of triglyceride-rich lipoproteins. *Apo-E* - **Apolipoprotein E** (ApoE) is crucial for the receptor-mediated uptake of **chylomicron remnants** and **VLDL remnants** by the liver. - While involved in remnant clearance, it is not the primary apolipoprotein for the initial transport of dietary cholesterol from the intestine within intact chylomicrons.

Q: What is the primary glycerol-containing absorption product of dietary triglycerides in the gut?

Mono acyl glycerol. ***Monoacylglycerol (2-MAG)*** - **Pancreatic lipase** hydrolyzes dietary triglycerides at positions 1 and 3, producing **2-monoacylglycerol** and **free fatty acids** as the two major products. - As the **primary glycerol-containing product**, 2-monoacylglycerol constitutes approximately **25% of digested lipid mass** and is essential for efficient **triglyceride resynthesis** in enterocytes. - Both 2-MAG and fatty acids are packaged into **mixed micelles** and co-absorbed, but 2-MAG is the predominant form containing the **intact glycerol backbone**. *Fatty acids* - **Free fatty acids** are co-absorbed with 2-monoacylglycerol in approximately a **2:1 molar ratio** (2 fatty acids per 1 monoacylglycerol). - While quantitatively significant, fatty acids do **not contain the glycerol backbone** structure. - Both products are required for efficient absorption and subsequent **triglyceride resynthesis** within enterocytes. *Diacylglycerol* - **Diacylglycerol** is a minor intermediate product during triglyceride hydrolysis. - It is rapidly hydrolyzed further by **pancreatic lipase** to yield **monoacylglycerol** and free fatty acids. - Not a significant absorption product in the intestinal lumen. *Triglycerides* - **Intact triglycerides** are too large and hydrophobic to be absorbed directly across the intestinal brush border. - They must first undergo **enzymatic hydrolysis** by pancreatic lipase into smaller absorbable units (2-MAG and fatty acids).

Q: Which ketone body is primarily responsible for the metabolic acidosis seen in diabetic ketoacidosis?

Beta hydroxybutyric acid. ***Beta hydroxybutyric acid*** - While both acetoacetic acid and beta-hydroxybutyric acid are ketone bodies, **beta-hydroxybutyric acid** is the most abundant and thus the primary contributor to the **acidosis** in DKA. - In diabetic ketoacidosis, the liver produces an excess of ketone bodies from **fatty acid metabolism**, and beta-hydroxybutyrate comprises approximately **75-80%** of total ketone bodies (with a β-hydroxybutyrate:acetoacetate ratio of **3:1 or higher**, compared to 1:1 normally). - This quantitative predominance makes it the **primary acid** responsible for the anion gap metabolic acidosis in DKA. *Acetoacetic acid* - **Acetoacetic acid** is indeed a ketone body and contributes to acidosis, but it is typically present in **lower concentrations** (approximately 20%) compared to beta-hydroxybutyric acid. - It can be converted to **acetone**, another ketone body, but neither is the primary cause of severe metabolic acidosis. *Carbonic acid* - **Carbonic acid** (H2CO3) is part of the **bicarbonate buffering system** and is derived from carbon dioxide and water, playing a role in respiratory acidosis or alkalosis. - It is not a ketone body and is not directly responsible for the **anion gap metabolic acidosis** observed in DKA. *Lactic acid* - **Lactic acid** accumulation can cause **lactic acidosis**, which is another form of metabolic acidosis often seen in conditions of tissue hypoxia or liver failure. - However, it is fundamentally different from the **ketone body accumulation** that defines DKA.

Q: Acetyl CoA carboxylase is stimulated by all except which of the following?

Acyl CoA. ***Acyl CoA*** - **Acyl CoA** (specifically long-chain fatty acyl CoAs) is an **inhibitor** of acetyl CoA carboxylase (ACC), signifying an abundance of fatty acids and a need to reduce further synthesis. - This feedback inhibition helps regulate **fatty acid synthesis**, ensuring that the pathway is downregulated when sufficient fatty acids are present. *Citrate* - **Citrate** is a potent **allosteric activator** of acetyl CoA carboxylase, indicating a high energy state and excess mitochondrial acetyl CoA, which can be channeled into fatty acid synthesis. - Its presence promotes the polymerization of ACC monomers into active polymers, enhancing enzyme activity. *ATP* - **ATP** is required as a substrate for the carboxylation reaction catalyzed by ACC, providing the energy for the formation of **malonyl CoA**. - High levels of ATP indirectly signal a state of energy abundance, which favors anabolic processes like fatty acid synthesis. *Insulin* - **Insulin** is a hormonal activator of acetyl CoA carboxylase, promoting its dephosphorylation via **protein phosphatase 2A**. - This dephosphorylation leads to increased enzyme activity, stimulating **fatty acid synthesis** in response to high blood glucose after a meal.

Q: Which enzyme deficiency causes Niemann-Pick disease, leading to lysosomal dysfunction?

Sphingomyelinase. ***Sphingomyelinase*** - Niemann-Pick disease types A and B are caused by a deficiency in the enzyme **acid sphingomyelinase**, which is responsible for the breakdown of **sphingomyelin**. - This deficiency leads to the accumulation of **sphingomyelin** within lysosomes of various tissues, particularly in the brain, spleen, liver, and lungs. *Ceramidase* - A deficiency in **ceramidase** causes Farber disease, a rare lysosomal storage disorder characterized by joint deformities, subcutaneous nodules, and hoarseness. - While both ceramidase and sphingomyelinase are involved in **sphingolipid metabolism**, their specific substrates and the resulting clinical pathologies differ. *Phospholipase C* - **Phospholipase C** plays a crucial role in signal transduction by cleaving phospholipids, but its deficiency is not directly linked to Niemann-Pick disease. - Deficiencies in phospholipase C activity are associated with various cellular dysfunctions but not lysosomal storage disorders like Niemann-Pick. *Beta-galactosidase* - A deficiency in **beta-galactosidase** causes GM1 gangliosidosis and Morquio syndrome type B, both of which are lysosomal storage disorders. - These conditions involve the accumulation of specific **glycosphingolipids** or **keratan sulfate**, rather than sphingomyelin.

Q: Enzyme replacement therapy is available for which of the following lysosomal storage disorders?

Gaucher's disease. ***Gaucher's disease*** - Enzyme replacement therapy (ERT) with **imiglucerase**, **velaglucerase alfa**, or **taliglucerase alfa** is a highly effective treatment for Type 1 and Type 3 Gaucher's disease - It provides the deficient enzyme **glucocerebrosidase** (β-glucosidase), which breaks down glucocerebroside, preventing its accumulation in macrophages - ERT significantly reduces hepatosplenomegaly, improves bone disease, and corrects cytopenias *Niemann-Pick disease Type C* - **No enzyme replacement therapy** is currently available for Niemann-Pick disease Type C - This disorder involves defective cholesterol trafficking, not a single enzyme deficiency amenable to replacement - Treatment is primarily **supportive** with miglustat for neurological symptoms in some cases *Tay-Sachs disease* - There is currently **no effective enzyme replacement therapy** for Tay-Sachs disease - The deficient enzyme **hexosaminidase A** cannot effectively cross the **blood-brain barrier** to reach affected neurons in the CNS - Treatment is purely **supportive and palliative** *None of the above* - This option is incorrect because **Gaucher's disease** has well-established and FDA-approved enzyme replacement therapy

Question 1

In beta-oxidation of fatty acids, carnitine is required for:

Accepted Answer

Transport of long chain fatty acid to mitochondrial inner layer

Answer

Conversion of long chain fatty acids to short chain fatty acids

Answer

Transport of long chain fatty acid across the outer mitochondrial membrane

Answer

Conversion of short chain fatty acids to medium chain fatty acids

Question 2

Tay-Sachs disease is due to a deficiency of which enzyme?

Accepted Answer

Hexosaminidase A

Answer

Hexosaminidase B

Answer

α-galactosidase

Answer

Sphingomyelinase

Question 3

Congenital 17-hydroxylase deficiency leads to hypertension due to the accumulation of?

Accepted Answer

Deoxycorticosterone

Answer

Cortisol

Answer

17-hydroxypregnenolone

Answer

17-hydroxy progesterone

Question 4

The fatty acid present in breast milk which is important for growth and CNS development is:

Accepted Answer

Docosahexaenoic acid

Answer

Palmitic acid

Answer

Linolenic acid

Answer

Linoleic acid

Question 5

Dietary cholesterol is transported from the intestine to the liver by:

Accepted Answer

Apo-B

Answer

Apo-E

Answer

Apo-A

Answer

Apo-C

Question 6

What is the primary glycerol-containing absorption product of dietary triglycerides in the gut?

Accepted Answer

Mono acyl glycerol

Answer

Fatty acids

Answer

Diacyl glycerol

Answer

Triglycerides

Question 7

Which ketone body is primarily responsible for the metabolic acidosis seen in diabetic ketoacidosis?

Accepted Answer

Beta hydroxybutyric acid

Answer

Carbonic acid

Answer

Acetoacetic acid

Answer

Lactic acid

Question 8

Acetyl CoA carboxylase is stimulated by all except which of the following?

Accepted Answer

Acyl CoA

Answer

ATP

Answer

Insulin

Answer

Citrate

Question 9

Which enzyme deficiency causes Niemann-Pick disease, leading to lysosomal dysfunction?

Accepted Answer

Sphingomyelinase

Answer

Ceramidase

Answer

Phospholipase C

Answer

Beta-galactosidase

Question 10

Enzyme replacement therapy is available for which of the following lysosomal storage disorders?

Accepted Answer

Gaucher's disease

Answer

Tay-Sachs disease

Answer

None of the above

Answer

Niemann-Pick disease Type C

Lipid Metabolism — MCQs

Lipid Metabolism — MCQs

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