A 13-year-old girl is brought to the physician by her mother because of a 1-month history of abnormal movements of her muscles that she cannot control. She has a younger brother with cognitive disabilities and epilepsy. Examination shows frequent, brief, involuntary contractions of the muscle groups of the upper arms, legs, and face that can be triggered by touch. An EEG shows generalized epileptiform activity. A trichrome stain of a skeletal muscle biopsy specimen shows muscle fibers with peripheral red inclusions that disrupt the normal fiber contour. Which of the following is the most likely underlying mechanism of the patient's symptoms?
Q82
A 30-year-old man presents with dark urine and fatigue. The patient states that the symptoms started 2 days ago. Since yesterday, he also noticed that his eyes look yellow. The past medical history is significant for recent right ear pain diagnosed 3 days ago as acute otitis media, which he was prescribed trimethoprim-sulfamethoxazole. He currently does not take any other medications on a daily basis. The patient was adopted and has no knowledge of his family history. The vital signs include: temperature 37.0°C (98.6°F), blood pressure 100/75 mm Hg, pulse 105/min, respiratory rate 15/min, and oxygen saturation 100% on room air. On physical exam, the patient is alert and cooperative. The cardiac exam is significant for an early systolic murmur that is best heard at the 2nd intercostal space, midclavicular line. There is scleral icterus present. The peripheral blood smear shows the presence of bite cells and Heinz bodies. Which of the following laboratory findings would most likely be present in this patient?
Q83
A 2-day-old boy is examined on day of discharge from the newborn nursery. He was born at 39 weeks by vaginal delivery to a primigravid mother. The pregnancy and delivery were uncomplicated, and the baby has been stooling, urinating, and feeding normally. Both the patient’s mother and father have no known past medical history and are found to have normal hemoglobin electrophoresis results. Compared to adult hemoglobin, the infant’s predominant hemoglobin is most likely to exhibit which of the following properties?
Q84
A 25-day-old newborn is brought to the pediatrician for lethargy, poor muscle tone, and feeding difficulty with occasional regurgitation that recently turned into projectile vomiting. The child was born via vaginal delivery without complications. On examination, the vital signs include: pulse 130/min, respiratory rate 30/min, blood pressure 96/60 mm Hg, and temperature 36.5°C (97.7°F). The physical examination shows a broad nasal bridge, oral thrush, hepatosplenomegaly, and generalized hypotonia. Further tests of blood and urine samples help the pediatrician to diagnose the child with an enzyme deficiency. More extensive laboratory testing reveals normal levels of citrulline and hypoglycemia. There are also elevated levels of ketone bodies, glycine, and methylmalonic acid. Which of the following is the product of the reaction catalyzed by the deficient enzyme in this patient?
Q85
A 26-year-old woman, gravida 1, para 0, at 22 weeks' gestation is brought to the emergency department by her husband because of a 2-day history of confusion and falls. Pregnancy has been complicated by excessive vomiting and an 8-kg (17-lb) weight loss over the past 10 weeks. Physical examination shows vertical nystagmus and a wide-based gait. Muscle tone and tendon reflexes are diminished in all extremities. An MRI of the brain shows periventricular diffusion abnormalities. Treatment is initiated with a vitamin followed by a dextrose infusion. The primary reason to administer the vitamin first is to ensure the function of which of the following enzymes?
Q86
A 52-year-old man is brought to the emergency department after being found by police confused and lethargic in the park. The policemen report that the patient could not recall where he was or how he got there. Medical history is significant for multiple prior hospitalizations for acute pancreatitis. He also has scheduled visits with a psychiatrist for managing his depression and substance abuse. On physical examination, the patient was found to have horizontal nystagmus and a wide-based gait with short-spaced steps. The patient is started on appropriate medication and admitted to the medicine floor. He was re-evaluated after treatment implementation and currently does not appear confused. When asked how he got to the hospital, the patient says, "I remember leaving my wallet here and thought I should pick it up." On cognitive testing the patient is noted to have impairments in judgement, sequencing tasks, and memory. Which of the following enzymes was most likely impaired in this patient?
Q87
A group of investigators discovers a novel monomeric enzyme that cleaves glutamate-valine bonds in a bacterial exotoxin. The substrate binding site of the enzyme is rich in aspartate. A sample of the enzyme is added to two serum samples containing the bacterial exotoxin. One sample is assigned a test condition while the other is maintained as the control. The averaged results of several trials comparing Vmax and Km between control serum and test serum are shown.
Vmax (μmol/min) Km (mM)
Control serum 13.2 81.2
Test serum 28.8 80.9
Which of the following conditions in the test serum would best explain these findings?
Q88
A 3-day-old female newborn is brought to the emergency department because of fever, poor feeding, and irritability for 6 hours. She was delivered at home at 39 weeks' gestation and delivery was uncomplicated. The mother had no prenatal care. Her temperature is 39.8°C (103.6°F), pulse is 172/min, respirations are 58/min, and blood pressure is 74/45 mm Hg. She appears lethargic. Physical examination shows expiratory grunting and nasal flaring. Serum studies show elevated levels of interleukin-6. Which of the following is the most likely effect of this laboratory finding?
Q89
A 9-month-old girl is brought to the physician because of a 1-month history of poor feeding and irritability. She is at the 15th percentile for height and 5th percentile for weight. Examination shows hypotonia and wasting of skeletal muscles. Cardiopulmonary examination shows no abnormalities. There is hepatomegaly. Her serum glucose is 61 mg/dL, creatinine kinase is 100 U/L, and lactic acid is within the reference range. Urine ketone bodies are elevated. Which of the following enzymes is most likely deficient in this patient?
Q90
An investigator is studying vitamin D metabolism in mice. He induces a gene mutation that interferes with the function of an enzyme in the renal proximal tubules that is required for vitamin D activation. He then measures serum levels of various metabolites. Production of which of the following will be impaired in this mouse?
Metabolism US Medical PG Practice Questions and MCQs
Question 81: A 13-year-old girl is brought to the physician by her mother because of a 1-month history of abnormal movements of her muscles that she cannot control. She has a younger brother with cognitive disabilities and epilepsy. Examination shows frequent, brief, involuntary contractions of the muscle groups of the upper arms, legs, and face that can be triggered by touch. An EEG shows generalized epileptiform activity. A trichrome stain of a skeletal muscle biopsy specimen shows muscle fibers with peripheral red inclusions that disrupt the normal fiber contour. Which of the following is the most likely underlying mechanism of the patient's symptoms?
A. CTG trinucleotide repeat expansion
B. Mutation of the methyl-CpG binding protein 2 gene
C. Truncated dystrophin protein
D. Autoimmune endomysial destruction
E. Defective oxidative phosphorylation (Correct Answer)
Explanation: ***Defective oxidative phosphorylation***
- The constellation of **uncontrolled muscle movements (myoclonus)**, **epilepsy**, and the brother's **cognitive disabilities** strongly suggests a **mitochondrial disorder**.
- **Ragged red fibers** on trichrome stain of skeletal muscle biopsy are pathognomonic for **mitochondrial myopathies**, indicating defective oxidative phosphorylation due to abnormal mitochondrial aggregates.
*CTG trinucleotide repeat expansion*
- This is characteristic of **Myotonic Dystrophy**, which primarily presents with **myotonia** (delayed muscle relaxation), progressive muscle weakness, and often cataracts, rather than prominent myoclonus and seizures.
- While muscle weakness can occur, the specific biopsy findings and prominent myoclonus point away from this diagnosis.
*Mutation of the methyl-CpG binding protein 2 gene*
- A mutation in the **MECP2 gene** causes **Rett Syndrome**, an X-linked dominant disorder seen almost exclusively in girls.
- It involves normal development for 6-18 months followed by regression, loss of purposeful hand movements, **stereotypical hand-wringing**, and microcephaly, which are not described here.
*Truncated dystrophin protein*
- A truncated dystrophin protein causes **Duchenne Muscular Dystrophy**, an X-linked recessive disorder leading to progressive muscle weakness, **Gowers' sign**, and elevated creatine kinase.
- This condition does not typically present with myoclonus or the characteristic ragged red fibers, nor does it typically involve the sibling's intellectual disability and epilepsy in this manner.
*Autoimmune endomysial destruction*
- This mechanism is characteristic of **celiac disease**, which can have neurological symptoms like ataxia or peripheral neuropathy, but not typically the severe myoclonus, epilepsy, or muscle biopsy findings seen here.
- **Inflammatory myopathies** like polymyositis may show endomysial inflammation, but the clinical picture and specific biopsy findings (ragged red fibers) are not consistent.
Question 82: A 30-year-old man presents with dark urine and fatigue. The patient states that the symptoms started 2 days ago. Since yesterday, he also noticed that his eyes look yellow. The past medical history is significant for recent right ear pain diagnosed 3 days ago as acute otitis media, which he was prescribed trimethoprim-sulfamethoxazole. He currently does not take any other medications on a daily basis. The patient was adopted and has no knowledge of his family history. The vital signs include: temperature 37.0°C (98.6°F), blood pressure 100/75 mm Hg, pulse 105/min, respiratory rate 15/min, and oxygen saturation 100% on room air. On physical exam, the patient is alert and cooperative. The cardiac exam is significant for an early systolic murmur that is best heard at the 2nd intercostal space, midclavicular line. There is scleral icterus present. The peripheral blood smear shows the presence of bite cells and Heinz bodies. Which of the following laboratory findings would most likely be present in this patient?
A. Decreased indirect bilirubin levels
B. Decreased reticulocyte count
C. Increased serum lactate dehydrogenase (LDH) (Correct Answer)
D. Increased serum haptoglobin
E. Decreased mean corpuscular volume
Explanation: ***Increased serum lactate dehydrogenase (LDH)***
- The patient's symptoms (dark urine, fatigue, jaundice), recent trimethoprim-sulfamethoxazole use, and peripheral blood smear findings (bite cells, Heinz bodies) are classic for **G6PD deficiency** with acute **hemolytic anemia**.
- **LDH** is an intracellular enzyme found in red blood cells, and its release into the bloodstream is a marker of **cell lysis**, which is elevated in hemolytic anemia due to the breakdown of red blood cells.
*Decreased indirect bilirubin levels*
- In **hemolytic anemia**, there is an increased breakdown of red blood cells, leading to a surplus of **unconjugated (indirect) bilirubin** that overwhelms the liver's capacity for conjugation.
- Therefore, **indirect bilirubin levels** would be **increased**, not decreased, contributing to the observed jaundice.
*Decreased reticulocyte count*
- The body compensates for acute hemolytic anemia by increasing red blood cell production in the bone marrow, which is reflected by an **increased reticulocyte count**.
- A **decreased reticulocyte count** would suggest bone marrow suppression or aplastic anemia, which is not indicated here.
*Increased serum haptoglobin*
- **Haptoglobin** is a protein that binds to free hemoglobin released during red blood cell destruction. In hemolytic anemia, haptoglobin is rapidly consumed and cleared from the blood.
- Thus, **serum haptoglobin levels** would be **decreased**, not increased, as it is used used up in an attempt to clear the free hemoglobin.
*Decreased mean corpuscular volume*
- **Mean corpuscular volume (MCV)** measures the average size of red blood cells. G6PD deficiency with hemolytic anemia is typically a **normocytic anemia**, meaning the red blood cells are of normal size.
- A **decreased MCV** would suggest microcytic anemia, such as iron deficiency or thalassemias, which is not consistent with the clinical picture or blood smear findings.
Question 83: A 2-day-old boy is examined on day of discharge from the newborn nursery. He was born at 39 weeks by vaginal delivery to a primigravid mother. The pregnancy and delivery were uncomplicated, and the baby has been stooling, urinating, and feeding normally. Both the patient’s mother and father have no known past medical history and are found to have normal hemoglobin electrophoresis results. Compared to adult hemoglobin, the infant’s predominant hemoglobin is most likely to exhibit which of the following properties?
A. Decreased affinity for 2,3-bisphosphoglycerate (Correct Answer)
B. More likely to form hexagonal crystals
C. More likely to cause red blood cell sickling
D. Lower affinity for binding oxygen
E. Increased affinity for 2,3-bisphosphoglycerate
Explanation: ***Decreased affinity for 2,3-bisphosphoglycerate***
- The baby's predominant hemoglobin is **hemoglobin F (HbF)**, which has a **gamma globin subunit** instead of the beta globin subunit found in adult hemoglobin (HbA).
- The gamma subunit of HbF results in a **reduced binding affinity to 2,3-bisphosphoglycerate (2,3-BPG)**, which in turn leads to a **higher affinity for oxygen** and more efficient oxygen transfer from the mother to the fetus.
*More likely to form hexagonal crystals*
- The formation of **hexagonal crystals** is characteristic of **hemoglobin C (HbC)** disease, a variant of adult hemoglobin, which is not predominant in a newborn.
- The parents have normal hemoglobin electrophoresis, ruling out the inheritance of significant hemoglobinopathies like HbC in a homozygous or compound heterozygous state.
*More likely to cause red blood cell sickling*
- **Red blood cell sickling** is a hallmark of **sickle cell anemia**, caused by hemoglobin S (HbS) which is an abnormal adult hemoglobin, not fetal hemoglobin.
- The parents have normal hemoglobin electrophoresis, meaning they are unlikely to carry the sickle cell trait, and the newborn's predominant HbF actually protects against sickling.
*Lower affinity for binding oxygen*
- HbF in newborns has a **higher affinity for oxygen** than adult hemoglobin (HbA) to facilitate efficient oxygen extraction from maternal blood across the placenta.
- A lower affinity for oxygen would be detrimental for a newborn as it would impair proper tissue oxygenation.
*Increased affinity for 2,3-bisphosphoglycerate*
- HbF has a **decreased affinity for 2,3-BPG**. An increased affinity for 2,3-BPG would lead to a reduction in oxygen binding affinity, which is the opposite of the physiological need in a newborn.
Question 84: A 25-day-old newborn is brought to the pediatrician for lethargy, poor muscle tone, and feeding difficulty with occasional regurgitation that recently turned into projectile vomiting. The child was born via vaginal delivery without complications. On examination, the vital signs include: pulse 130/min, respiratory rate 30/min, blood pressure 96/60 mm Hg, and temperature 36.5°C (97.7°F). The physical examination shows a broad nasal bridge, oral thrush, hepatosplenomegaly, and generalized hypotonia. Further tests of blood and urine samples help the pediatrician to diagnose the child with an enzyme deficiency. More extensive laboratory testing reveals normal levels of citrulline and hypoglycemia. There are also elevated levels of ketone bodies, glycine, and methylmalonic acid. Which of the following is the product of the reaction catalyzed by the deficient enzyme in this patient?
A. Succinyl-CoA (Correct Answer)
B. Methylmalonyl-CoA
C. Enoyl-CoA
D. Pyruvate
E. Acetyl-CoA
Explanation: ***Succinyl-CoA***
- The constellation of **poor feeding**, **vomiting**, **hypotonia**, **hypoglycemia**, **ketonemia**, elevated **glycine**, and **methylmalonic acid** is classic for **methylmalonic acidemia**.
- This condition is caused by a deficiency of **methylmalonyl-CoA mutase**, which catalyzes the conversion of **methylmalonyl-CoA** to **succinyl-CoA**.
*Methylmalonyl-CoA*
- **Methylmalonyl-CoA** is the **substrate** that accumulates due to the deficient enzyme, not the product.
- Its accumulation leads to the characteristic **methylmalonic aciduria/acidemia**.
*Enoyl-CoA*
- **Enoyl-CoA** is an intermediate in **fatty acid beta-oxidation** and is not directly involved in the methylmalonyl-CoA mutase pathway.
- Deficiencies related to enoyl-CoA would lead to disorders of **fatty acid metabolism**, which present differently.
*Pyruvate*
- **Pyruvate** is a product of **glycolysis** and a precursor to the **Krebs cycle** and gluconeogenesis, but it is not directly affected by methylmalonyl-CoA mutase deficiency.
- Disorders involving pyruvate metabolism typically present with **lactic acidosis**.
*Acetyl-CoA*
- **Acetyl-CoA** is an end-product of **fatty acid oxidation** and pyruvate dehydrogenase, and it's a key entry point into the **Krebs cycle**.
- While related to metabolic energy, it is not the direct product of the deficient reaction in **methylmalonic acidemia**.
Question 85: A 26-year-old woman, gravida 1, para 0, at 22 weeks' gestation is brought to the emergency department by her husband because of a 2-day history of confusion and falls. Pregnancy has been complicated by excessive vomiting and an 8-kg (17-lb) weight loss over the past 10 weeks. Physical examination shows vertical nystagmus and a wide-based gait. Muscle tone and tendon reflexes are diminished in all extremities. An MRI of the brain shows periventricular diffusion abnormalities. Treatment is initiated with a vitamin followed by a dextrose infusion. The primary reason to administer the vitamin first is to ensure the function of which of the following enzymes?
A. Methionine synthase
B. α-Ketoglutarate dehydrogenase (Correct Answer)
C. Succinate dehydrogenase
D. Fatty acid synthase
E. Pyruvate carboxylase
Explanation: ***α-Ketoglutarate dehydrogenase***
- The patient's symptoms (confusion, ataxia/falls, nystagmus) and history of hyperemesis gravidarum with significant weight loss are highly suggestive of **Wernicke encephalopathy**, caused by **thiamine (vitamin B1) deficiency**.
- **Thiamine pyrophosphate**, the active form of thiamine, is a critical cofactor for several enzymes in carbohydrate metabolism, particularly **α-ketoglutarate dehydrogenase** in the **Krebs cycle**, and administering glucose without thiamine can exacerbate the deficiency by increasing demand for thiamine-dependent enzymes.
*Methionine synthase*
- **Methionine synthase** is an enzyme that requires **vitamin B12 (cobalamin)** and **folate** as cofactors, not thiamine.
- Deficiency in these vitamins can lead to megaloblastic anemia and neurological symptoms, but not the classic triad of Wernicke encephalopathy.
*Succinate dehydrogenase*
- **Succinate dehydrogenase** is a component of the **electron transport chain** and the **Krebs cycle**, but it does not directly require thiamine as a cofactor.
- This enzyme contains **flavin adenine dinucleotide (FAD)**, derived from **riboflavin (vitamin B2)**, as a prosthetic group.
*Fatty acid synthase*
- **Fatty acid synthase** is a multi-enzyme complex involved in **fatty acid synthesis** and primarily uses **NADPH** as a reducing agent.
- Its activity is not directly dependent on thiamine as a cofactor.
*Pyruvate carboxylase*
- **Pyruvate carboxylase** is an enzyme involved in **gluconeogenesis** and requires **biotin (vitamin B7)** as a cofactor.
- A deficiency in biotin would affect this enzyme, but it does not explain the clinical picture of Wernicke encephalopathy.
Question 86: A 52-year-old man is brought to the emergency department after being found by police confused and lethargic in the park. The policemen report that the patient could not recall where he was or how he got there. Medical history is significant for multiple prior hospitalizations for acute pancreatitis. He also has scheduled visits with a psychiatrist for managing his depression and substance abuse. On physical examination, the patient was found to have horizontal nystagmus and a wide-based gait with short-spaced steps. The patient is started on appropriate medication and admitted to the medicine floor. He was re-evaluated after treatment implementation and currently does not appear confused. When asked how he got to the hospital, the patient says, "I remember leaving my wallet here and thought I should pick it up." On cognitive testing the patient is noted to have impairments in judgement, sequencing tasks, and memory. Which of the following enzymes was most likely impaired in this patient?
A. Dopamine-β-hydroxylase
B. Transketolase (Correct Answer)
C. Methylmalonyl-CoA mutase
D. Pyruvate carboxylase
E. Methionine synthase
Explanation: ***Transketolase***
- This patient's presentation with **confusion, lethargy, nystagmus, wide-based gait**, and a history of **alcoholism (implied by recurrent pancreatitis and substance abuse)** is characteristic of **Wernicke-Korsakoff syndrome**, caused by **thiamine (B1) deficiency**.
- **Transketolase** is a crucial enzyme in the **pentose phosphate pathway** that requires **thiamine pyrophosphate (TPP)** as a cofactor. Its impairment is a direct consequence of thiamine deficiency.
*Dopamine-ß-hydroxylase*
- This enzyme is involved in the synthesis of **norepinephrine** from dopamine.
- Its impairment is not directly associated with Wernicke-Korsakoff syndrome or thiamine deficiency.
*Methylmalonyl-CoA mutase*
- This enzyme is involved in the metabolism of **odd-chain fatty acids** and some amino acids, requiring **vitamin B12** as a cofactor.
- Its deficiency leads to **methylmalonic aciduria** and neurological symptoms distinct from Wernicke-Korsakoff syndrome, such as **subacute combined degeneration** of the spinal cord.
*Pyruvate carboxylase*
- **Pyruvate carboxylase** is an enzyme involved in **gluconeogenesis** and requires **biotin** as a cofactor.
- Deficiencies typically lead to severe **lactic acidosis** and neurological symptoms, but not the specific triad seen in Wernicke-Korsakoff syndrome.
*Methionine synthase*
- **Methionine synthase** is an enzyme involved in the **folate cycle** and requires **vitamin B12** as a cofactor.
- Its deficiency leads to megaloblastic anemia and neurological symptoms, similar to methylmalonyl-CoA mutase deficiency, not Wernicke-Korsakoff syndrome.
Question 87: A group of investigators discovers a novel monomeric enzyme that cleaves glutamate-valine bonds in a bacterial exotoxin. The substrate binding site of the enzyme is rich in aspartate. A sample of the enzyme is added to two serum samples containing the bacterial exotoxin. One sample is assigned a test condition while the other is maintained as the control. The averaged results of several trials comparing Vmax and Km between control serum and test serum are shown.
Vmax (μmol/min) Km (mM)
Control serum 13.2 81.2
Test serum 28.8 80.9
Which of the following conditions in the test serum would best explain these findings?
A. Presence of a reversible competitive inhibitor
B. Increased exotoxin concentration
C. Increased enzyme concentration (Correct Answer)
D. Presence of an irreversible competitive inhibitor
E. Increased serum pH
Explanation: ***Increased enzyme concentration***
- An increase in enzyme concentration directly leads to a higher **Vmax** because there are more active sites available to convert substrate into product.
- The **Km** (substrate concentration at half Vmax) remains unchanged as the enzyme's affinity for the substrate is not altered, only the total number of enzyme molecules.
*Presence of a reversible competitive inhibitor*
- A **competitive inhibitor** would increase the **apparent Km** (making it seem like the enzyme has lower affinity for the substrate) because it competes with the substrate for the active site.
- The **Vmax** would remain unchanged, as a sufficiently high substrate concentration can overcome the inhibition.
*Increased exotoxin concentration*
- Increasing the substrate (**exotoxin**) concentration within the range where the enzyme is not saturated would increase the reaction rate up to **Vmax**, but it would not change the intrinsic **Vmax** or **Km** of the enzyme.
- If the enzyme is already saturated, increasing substrate concentration further will not affect the rate.
*Presence of an irreversible competitive inhibitor*
- An **irreversible inhibitor** permanently binds to the enzyme, effectively reducing the concentration of functional enzyme.
- This would lead to a decrease in **Vmax** because fewer enzyme molecules are available for catalysis.
- Note: True competitive inhibitors are reversible; this option tests understanding that irreversible inhibition reduces functional enzyme concentration and thus Vmax.
*Increased serum pH*
- Changing the **pH** away from the enzyme's optimal pH would typically lead to a decrease in enzyme activity, thereby reducing the **Vmax** and potentially altering the **Km** due to changes in enzyme conformation.
- The observed increase in **Vmax** and unchanged **Km** do not align with a deviation from optimal pH.
Question 88: A 3-day-old female newborn is brought to the emergency department because of fever, poor feeding, and irritability for 6 hours. She was delivered at home at 39 weeks' gestation and delivery was uncomplicated. The mother had no prenatal care. Her temperature is 39.8°C (103.6°F), pulse is 172/min, respirations are 58/min, and blood pressure is 74/45 mm Hg. She appears lethargic. Physical examination shows expiratory grunting and nasal flaring. Serum studies show elevated levels of interleukin-6. Which of the following is the most likely effect of this laboratory finding?
A. Decreased synthesis of hepcidin
B. Decreased expression of MHC class II
C. Increased release of fibrinogen (Correct Answer)
D. Increased classical activation of macrophages
E. Increased production of IgE
Explanation: ***Increased release of fibrinogen***
- **Interleukin-6 (IL-6)** is a major **pro-inflammatory cytokine** that stimulates the liver to produce **acute phase reactants**, including **fibrinogen**.
- This increase in fibrinogen is part of the body's non-specific immune response to infection and inflammation, leading to elevated inflammatory markers like **ESR**.
*Decreased synthesis of hepcidin*
- **Hepcidin** synthesis is *increased* by IL-6, not decreased, as part of the body's response to inflammation to limit iron availability to pathogens.
- High levels of hepcidin lead to **anemia of chronic disease** by inhibiting iron absorption and release from macrophages.
*Decreased expression of MHC class II*
- IL-6 generally *enhances* immune responses, and while it doesn't directly increase MHC class II expression on antigen-presenting cells, reduced expression is not a typical effect.
- **MHC class II** expression is primarily regulated by cytokines like **interferon-gamma** and helps present antigens to T-helper cells.
*Increased classical activation of macrophages*
- **Classical activation of macrophages** (M1 polarization) is primarily driven by **interferon-gamma (IFN-γ)** and **TNF-α**, often in response to pathogen signals.
- While IL-6 can contribute to the overall inflammatory environment, it is not the primary cytokine for classical macrophage activation; rather, it often promotes alternative (M2) phenotypes or has pleiotropic effects.
*Increased production of IgE*
- **IgE production** is primarily associated with **allergic reactions** and **parasitic infections**, driven by cytokines like **IL-4** and **IL-13**.
- IL-6 is not directly involved in stimulating IgE synthesis; its main roles are in inflammation, hematopoiesis, and the acute phase response.
Question 89: A 9-month-old girl is brought to the physician because of a 1-month history of poor feeding and irritability. She is at the 15th percentile for height and 5th percentile for weight. Examination shows hypotonia and wasting of skeletal muscles. Cardiopulmonary examination shows no abnormalities. There is hepatomegaly. Her serum glucose is 61 mg/dL, creatinine kinase is 100 U/L, and lactic acid is within the reference range. Urine ketone bodies are elevated. Which of the following enzymes is most likely deficient in this patient?
A. Glucose-6-phosphatase
B. Muscle phosphorylase
C. Acid alpha-glucosidase
D. Glycogen debrancher (Correct Answer)
E. Glucocerebrosidase
Explanation: ***Glycogen debrancher***
- The patient's symptoms of **hepatomegaly**, **hypoglycemia**, **poor feeding**, **growth failure**, and **elevated urine ketones** in the presence of normal lactic acid suggest Type III glycogen storage disease (Cori disease), caused by a deficiency in **glycogen debrancher enzyme**.
- **Muscle wasting** and **hypotonia** are also consistent with Type III GSD, as the debranching enzyme is present in both liver and muscle.
*Glucose-6-phosphatase*
- Deficiency in **glucose-6-phosphatase** (Type I GSD, Von Gierke disease) also presents with **hepatomegaly** and **hypoglycemia**.
- However, Type I GSD is characterized by **lactic acidosis**, which is explicitly stated as normal in this patient, and **hyperlipidemia**, which is not mentioned.
*Muscle phosphorylase*
- Deficiency in **muscle phosphorylase** (Type V GSD, McArdle disease) primarily affects skeletal muscle, causing **exercise intolerance** and **muscle pain**.
- It does not typically present with **hypoglycemia**, **hepatomegaly**, or **growth failure** in infancy.
*Acid alpha-glucosidase*
- Deficiency in **acid alpha-glucosidase** (Type II GSD, Pompe disease) causes accumulation of glycogen in lysosomes, leading to severe **cardiomyopathy**, **hypotonia**, and **muscle weakness**.
- While hypotonia is present, the absence of **cardiomegaly** and significant **liver involvement** makes this diagnosis less likely.
*Glucocerebrosidase*
- Deficiency in **glucocerebrosidase** causes Gaucher disease, a lysosomal storage disorder, not a glycogen storage disorder.
- Symptoms include **hepatosplenomegaly**, **bone crises**, and neurological symptoms, but not **hypoglycemia** or isolated muscle wasting directly related to glycogen metabolism.
Question 90: An investigator is studying vitamin D metabolism in mice. He induces a gene mutation that interferes with the function of an enzyme in the renal proximal tubules that is required for vitamin D activation. He then measures serum levels of various metabolites. Production of which of the following will be impaired in this mouse?
A. Ergocalciferol
B. Cholecalciferol
C. 7-dehydrocholesterol
D. 25-hydroxyvitamin D
E. 1,25-dihydroxyvitamin D (calcitriol) (Correct Answer)
Explanation: ***1,25-dihydroxyvitamin D (calcitriol)***
- This is the **biologically active form** of vitamin D, produced in the kidney by the **1α-hydroxylase enzyme** in the renal proximal tubules.
- A mutation interfering with this enzyme would directly impair the conversion of 25-hydroxyvitamin D to **1,25-dihydroxyvitamin D**, the active form.
- This enzyme adds the second hydroxyl group at position 1, creating the dihydroxy form (calcitriol).
*Ergocalciferol*
- This is **vitamin D2**, obtained from dietary sources (plants, supplements) and is not produced endogenously in the body.
- Its production would not be directly affected by a renal tubular enzyme defect.
*Cholecalciferol*
- This is **vitamin D3**, primarily synthesized in the skin upon exposure to sunlight or obtained from animal-based dietary sources.
- Its production occurs before any renal activation steps, so it would not be impaired.
*7-dehydrocholesterol*
- This is a **precursor molecule** in the skin that is converted to cholecalciferol (vitamin D3) upon UV radiation.
- Its levels would not be directly affected by a defect in renal vitamin D activation.
*25-hydroxyvitamin D*
- This is the **storage form** of vitamin D, produced in the liver from cholecalciferol or ergocalciferol by the 25-hydroxylase enzyme.
- Its production occurs prior to the renal activation step and would therefore not be impaired by a defect in the renal tubules.
