Lipid metabolism Practice Questions

Q: A 3-year-old girl presents with progressive neurodegeneration, a cherry-red spot on fundoscopic examination, and hepatosplenomegaly. Bone marrow biopsy reveals large macrophages with foamy cytoplasm. Enzyme assay of leukocytes shows markedly reduced activity of a lysosomal hydrolase. Which of the following correctly identifies the deficient enzyme and its accumulating substrate in this condition?

Sphingomyelinase; sphingomyelin. ***Sphingomyelinase; sphingomyelin*** - The presence of **hepatosplenomegaly**, **neurodegeneration**, and a **cherry-red spot** on the macula points directly to **Niemann-Pick disease (Type A)**. - Histology showing large macrophages with **foamy cytoplasm** confirms the accumulation of **sphingomyelin** due to a deficiency in **sphingomyelinase**. *β-glucocerebrosidase; glucocerebroside* - This deficiency causes **Gaucher disease**, which presents with hepatosplenomegaly but fundamentally lacks the **cherry-red spot**. - Bone marrow biopsy in Gaucher's would show "**crinkled tissue paper**" macrophages rather than the **foamy cells** described here. *Hexosaminidase A; GM2 ganglioside* - Deficiency leads to **Tay-Sachs disease**, which features a **cherry-red spot** and neurodegeneration similar to Niemann-Pick. - It is distinguished by the **absence of hepatosplenomegaly**, as there is no systemic involvement of visceral organs. *α-galactosidase A; globotriaosylceramide* - This deficiency causes **Fabry disease**, an X-linked disorder characterized by **angiokeratomas**, peripheral neuropathy, and renal failure. - It does not present with a **cherry-red spot** or the rapid neurodegeneration seen in this case. *Galactocerebrosidase; galactocerebroside* - Deficiency results in **Krabbe disease**, which presents with developmental delay and optic atrophy, but no **cherry-red spot**. - Histologically, it is characterized by the presence of multinucleated **globoid cells** rather than foamy macrophages.

Q: A 3-year-old girl is evaluated for recurrent episodes of vomiting, lethargy, and hyperammonemia that worsen after high-protein meals. Plasma amino acid analysis reveals elevated glutamine and alanine with low citrulline. Urine orotic acid is markedly elevated. Her older brother died at age 2 years with a similar presentation. She is a symptomatic heterozygous female due to skewed X-inactivation. The condition follows an X-linked recessive inheritance pattern. Based on the biochemical findings and the inheritance pattern, which enzyme is most likely deficient in this patient?

Ornithine transcarbamylase. ***Ornithine transcarbamylase*** - **Ornithine transcarbamylase (OTC)** deficiency is the most common urea cycle disorder and the only one that follows an **X-linked recessive** inheritance pattern, explaining the female's symptoms due to **skewed X-inactivation**. - The deficiency causes **hyperammonemia** and an accumulation of **carbamoyl phosphate**, which is shunted into the pyrimidine synthesis pathway, leading to the characteristic finding of markedly elevated **urine orotic acid**. *Carbamoyl phosphate synthetase I* - Like OTC deficiency, this presents with severe **hyperammonemia** and low **citrulline**, but it results in **low orotic acid** levels. - It follows an **autosomal recessive** inheritance pattern, which does not align with the X-linked pattern described in the scenario. *Argininosuccinate synthetase* - A deficiency here leads to **Citrullinemia**, characterized by massively **elevated citrulline** levels in the plasma, which contradicts the low levels seen in this patient. - This condition is inherited in an **autosomal recessive** manner and does not typically involve significant elevations in orotic acid. *Argininosuccinate lyase* - This deficiency leads to elevated **argininosuccinic acid** levels and moderately elevated **citrulline**, unlike the low citrulline found in this case. - Patients often present with **trichorrhexis nodosa** (brittle hair), and the inheritance pattern is **autosomal recessive**. *Arginase* - Arginase deficiency typically presents later in childhood with **spastic diplegia** and growth retardation rather than acute neonatal **hyperammonemia**. - It is characterized by significantly **elevated arginine** levels and is inherited in an **autosomal recessive** fashion.

Q: Colipase is an enzyme found in secretions from which of the following? (Recent NEET Pattern 2018)

Pancreas. ***Pancreas*** - The pancreas is the primary source of **colipase** secretion in the digestive system. - Colipase is an essential co-factor for **pancreatic lipase**, helping it to anchor to the surface of **lipid droplets** and digest triglycerides in the presence of bile salts. - Colipase is secreted by pancreatic acinar cells along with other pancreatic enzymes into the duodenum. *Salivary glands* - The salivary glands (parotid, submandibular, sublingual) produce saliva containing enzymes like **amylase** and **lingual lipase**. - These glands do not secrete colipase, which is involved in fat digestion in the small intestine, not in the mouth. *Gallbladder* - The gallbladder stores and releases **bile**, which aids in fat emulsification. - Bile does not contain colipase; colipase is produced by the pancreas and works synergistically with bile salts during fat digestion. *Small intestine* - The small intestine is where most nutrient absorption occurs and produces some enzymes (e.g., brush border enzymes like maltase, lactase). - The small intestine does not synthesize colipase; it receives colipase from pancreatic secretions via the pancreatic duct. *Liver* - The liver produces bile, which is stored in the gallbladder and released into the duodenum to emulsify fats. - The liver does not produce colipase; this enzyme is specifically secreted by pancreatic acinar cells.

Q: Name the mechanism shown as $X$ below.

Nonenzymatic decarboxylation. ***Nonenzymatic decarboxylation*** - The image shows **acetoacetate converting into acetone**, with the release of **carbon dioxide (CO2)**. This process is a spontaneous, **nonenzymatic decarboxylation** that occurs in conditions like diabetic ketoacidosis. - The absence of an enzyme indicated at "X" further supports that this is a **nonenzymatic reaction**. *Thiolase* - **Thiolase** is an enzyme involved in the synthesis of acetoacetyl CoA, and also in the breakdown of fatty acids, but not in the conversion of acetoacetate to acetone. - This enzyme catalyzes the **condensation of two acetyl-CoA** molecules to form acetoacetyl-CoA or the cleavage of acetoacetyl-CoA. *HMG CoA Lyase* - **HMG CoA lyase** is an enzyme that catalyzes the cleavage of HMG-CoA to **acetoacetate and acetyl-CoA** during ketogenesis. - It works upstream in the ketone body synthesis pathway, not directly converting acetoacetate to acetone. *HMG CoA synthase* - **HMG CoA synthase** is an enzyme that catalyzes the condensation of **acetoacetyl-CoA and acetyl-CoA** to form HMG-CoA, the first committed step of ketogenesis. - It works upstream in the pathway, not in the conversion of acetoacetate to acetone. *L-beta hydroxyl butyrate dehydrogenase* - The image already labels **beta-hydroxybutyrate dehydrogenase**, which interconverts **acetoacetate and beta-hydroxybutyrate** using NADH and NAD+. - This enzyme is responsible for the reversible reduction of acetoacetate to beta-hydroxybutyrate, and not for the formation of acetone.

Q: Which is the location of HMG CoA synthase in cholesterol metabolism?

2. ***2*** - HMG CoA synthase is a key enzyme in the cholesterol synthesis pathway, specifically converting acetoacetyl-CoA to **hydroxymethylglutaryl-CoA (HMG-CoA)**. - This step occurs in the **cytosol**, which is indicated by '2' in the diagram. - The cytosolic form of HMG-CoA synthase is specifically involved in cholesterol biosynthesis. *1* - '1' points to the **nucleus**, which is primarily involved in DNA replication and transcription, not cholesterol synthesis. - While gene expression control for cholesterol synthesis occurs here (e.g., SREBP regulation), the enzymatic reaction itself does not take place in the nucleus. *3* - '3' indicates the **smooth endoplasmic reticulum (SER)**, which is involved in later steps of cholesterol synthesis, such as the conversion of squalene to cholesterol. - However, the initial steps catalyzed by HMG CoA synthase occur in the cytosol, not directly on the SER. *4* - '4' points to a **mitochondrion**, which is involved in energy production through the citric acid cycle and oxidative phosphorylation. - Note: There is a mitochondrial HMG-CoA synthase, but it is involved in **ketone body synthesis**, not cholesterol metabolism. *5* - '5' represents another cellular structure not involved in the HMG-CoA synthase step of cholesterol synthesis. - The cholesterol synthesis pathway begins in the cytosol with the formation of HMG-CoA before proceeding to other compartments.

Q: A patient has multiple tendon xanthomas. Serum cholesterol ( $398 \mathrm{mg} / \mathrm{dL}$ ) and LDL ( 220 $\mathrm{mg} / \mathrm{dL}$ ) were found to be elevated. What is the most likely defect?

LDL receptor defect. ***LDL receptor defect*** - **Tendon xanthomas** are a classic sign of **familial hypercholesterolemia**, which is most commonly caused by a genetic defect in the **LDL receptor**. - **Elevated LDL cholesterol** levels are a hallmark of this condition, as dysfunctional LDL receptors lead to impaired clearance of LDL particles from the blood. *Lipoprotein lipase deficiency* - This condition primarily causes severe **hypertriglyceridemia** and can lead to **eruptive xanthomas**, but not typically tendon xanthomas. - While cholesterol levels might be elevated, the defining feature would be very high triglyceride levels, often exceeding 1000 mg/dL. *Apo E defect* - A defect in **ApoE** (specifically the **ApoE2/E2 genotype**) is associated with **familial dysbetalipoproteinemia** (Type III hyperlipoproteinemia). - This condition causes elevated remnants of chylomicrons and VLDL, leading to **palmar xanthomas**, but less commonly tendon xanthomas, and often presents with high triglyceride levels in addition to cholesterol. *Apo B-100 defect* - **Familial defective apoB-100** can present similarly to familial hypercholesterolemia with elevated LDL cholesterol. - However, this is much **rarer** than LDL receptor defects (affecting ~1:700 vs 1:250-500 for LDL receptor mutations). - The clinical presentation and lipid profile overlap significantly, but LDL receptor defects remain the most common cause of this clinical picture. *LCAT deficiency* - **Lecithin-cholesterol acyltransferase (LCAT)** deficiency leads to an accumulation of **unesterified cholesterol** in plasma and tissues. - This typically presents with **corneal opacities**, **hemolytic anemia**, and proteinuria, rather than predominantly tendon xanthomas and isolated severe LDL elevation.

Q: A patient presents with xanthomas on the Achilles tendon. What is the most likely diagnosis?

Familial hypercholesterolemia. ***Familial hypercholesterolemia*** - **Xanthomas** on the **Achilles tendon** are a classic clinical sign of familial hypercholesterolemia, along with significantly elevated **LDL-C levels**. - This condition is an **autosomal dominant** genetic disorder characterized by defects in the **LDL receptor** pathway, leading to impaired clearance of LDL from the blood. - **Tendon xanthomas** (especially Achilles and extensor tendons) are pathognomonic for this condition. *Tangier's disease* - Characterized by very low or absent **HDL-C (high-density lipoprotein cholesterol)** levels, leading to **cholesterol ester accumulation** in various tissues. - While it can cause lipid deposition, its hallmark is **enlarged, orange tonsils** and peripheral neuropathy, not typically Achilles tendon xanthomas. *Familial hyperchylomicronemia* - This disorder primarily involves elevated **chylomicrons** and **triglycerides**, presenting with **eruptive xanthomas** (small, red-yellow papules) but not typically tendon xanthomas. - It is often associated with **pancreatitis** and **lipemia retinalis**. *Familial dysbetalipoproteinemia* - Characterized by elevated levels of **cholesterol** and **triglycerides** due to accumulation of remnant lipoproteins (IDL). - While it can cause **xanthomas**, these are typically **palmar xanthomas** (xanthoma striata palmaris) and **tuberoeruptive xanthomas**, less commonly Achilles tendon xanthomas. *Familial combined hyperlipidemia* - Most common familial lipid disorder, characterized by elevated **LDL-C** and/or **triglycerides** with variable phenotype. - While it causes premature coronary artery disease, it typically does **not** cause tendon xanthomas, which distinguishes it from familial hypercholesterolemia. - Xanthomas, if present, are usually **xanthelasma** (around eyelids) rather than tendon xanthomas.

Question 1

A 3-year-old girl presents with progressive neurodegeneration, a cherry-red spot on fundoscopic examination, and hepatosplenomegaly. Bone marrow biopsy reveals large macrophages with foamy cytoplasm. Enzyme assay of leukocytes shows markedly reduced activity of a lysosomal hydrolase. Which of the following correctly identifies the deficient enzyme and its accumulating substrate in this condition?

Accepted Answer

Sphingomyelinase; sphingomyelin

Answer

β-glucocerebrosidase; glucocerebroside

Answer

Hexosaminidase A; GM2 ganglioside

Answer

α-galactosidase A; globotriaosylceramide

Answer

Galactocerebrosidase; galactocerebroside

Question 2

A 3-year-old girl is evaluated for recurrent episodes of vomiting, lethargy, and hyperammonemia that worsen after high-protein meals. Plasma amino acid analysis reveals elevated glutamine and alanine with low citrulline. Urine orotic acid is markedly elevated. Her older brother died at age 2 years with a similar presentation. She is a symptomatic heterozygous female due to skewed X-inactivation. The condition follows an X-linked recessive inheritance pattern. Based on the biochemical findings and the inheritance pattern, which enzyme is most likely deficient in this patient?

Accepted Answer

Ornithine transcarbamylase

Answer

Carbamoyl phosphate synthetase I

Answer

Argininosuccinate synthetase

Answer

Argininosuccinate lyase

Answer

Arginase

Question 3

Colipase is an enzyme found in secretions from which of the following? (Recent NEET Pattern 2018)

Accepted Answer

Pancreas

Answer

Salivary glands

Answer

Gallbladder

Answer

Small intestine

Answer

Liver

Question 4

Name the mechanism shown as $X$ below.

Accepted Answer

Nonenzymatic decarboxylation

Answer

Thiolase

Answer

HMG CoA Lyase

Answer

L-beta hydroxyl butyrate dehydrogenase

Answer

HMG CoA synthase

Question 5

Which is the location of HMG CoA synthase in cholesterol metabolism?

Accepted Answer

2

Answer

1

Answer

3

Answer

4

Answer

5

Question 6

An adult male presented with a protruding abdomen, diarrhea, visual symptoms, and neurological manifestations. His LDL is low. Based on the peripheral smear finding shown in the image, what is the likely diagnosis?

Accepted Answer

Abetalipoproteinemia

Answer

EDTA changes

Answer

Uremia

Answer

Burns

Answer

Liver disease

Question 7

A patient came to the hospital with severe abdominal pain, and lipase levels were elevated. On imaging, a stone is found in the common bile duct (CBD). Which enzyme is most likely elevated in this condition?

Accepted Answer

ALP

Answer

ALT

Answer

GGT

Answer

LDH

Answer

AST

Question 8

A patient came to the emergency room with severe abdominal pain. The serum triglyceride level was $1500 \mathrm{mg} / \mathrm{dL}$. What is the most likely defect?

Accepted Answer

Apo C-II

Answer

Apo B-48

Answer

Apo B-100

Answer

LDL receptor

Answer

Lipoprotein lipase

Question 9

A patient has multiple tendon xanthomas. Serum cholesterol ( $398 \mathrm{mg} / \mathrm{dL}$ ) and LDL ( 220 $\mathrm{mg} / \mathrm{dL}$ ) were found to be elevated. What is the most likely defect?

Accepted Answer

LDL receptor defect

Answer

Lipoprotein lipase deficiency

Answer

Apo E defect

Answer

LCAT deficiency

Answer

Apo B-100 defect

Question 10

A patient presents with xanthomas on the Achilles tendon. What is the most likely diagnosis?

Accepted Answer

Familial hypercholesterolemia

Answer

Tangier's disease

Answer

Familial hyperchylomicronemia

Answer

Familial dysbetalipoproteinemia

Answer

Familial combined hyperlipidemia

Lipid metabolism — MCQs

Lipid metabolism — MCQs

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