A 25-year-old woman comes to the emergency department because of a mild headache, dizziness, fatigue, and nausea over the past several hours. She has no history of serious illness and takes no medications. She lives in a basement apartment and uses a wood stove for heating. Her temperature is 36°C (96.8°F) and pulse is 120/min. Arterial blood gas analysis shows a carboxyhemoglobin level of 11% (N = < 1.5). Which of the following mechanisms is the underlying cause of this patient's symptoms?
Q192
A 34-year-old woman presents to the emergency department with prominent hypotension and tachycardia. On examination, she has a low central venous pressure and high cardiac output. Her temperature is 38.9°C (102.0°F). The physician suspects a bacterial infection with a gram-negative bacterium. Samples are sent to the lab. Meanwhile, high volumes of fluids were given, but the blood pressure did not improve. She was started on noradrenaline. At the biochemical level, a major reaction was induced as part of this patient’s presentation. Of the following vitamins, which one is related to the coenzyme that participates in this induced biochemical reaction?
Q193
A 26-year-old man comes to the physician for evaluation of fatigue, facial rash, hair loss, and tingling of his hands and feet. He has followed a vegetarian diet for the past 3 years and has eaten 8 raw egg whites daily for the past year in preparation for a bodybuilding competition. Physical examination shows conjunctival injections and a scaly, erythematous rash around the eyes and mouth. Laboratory studies show decreased activity of propionyl-coenzyme A carboxylase in peripheral blood lymphocytes. Which of the following substances is most likely to be decreased in this patient?
Q194
A 55-year-old man is evaluated in the clinic for several episodes of diarrhea during the past 2 months. He denies having fever or abdominal pain and states that his diarrhea has been getting worse despite the use of over-the-counter loperamide and bismuth compounds. Upon further questioning, he recalls having multiple episodes of a burning sensation in his neck and upper chest, associated with redness and flushing of his face, which lasted for a few seconds. Because of his hypertension and dyslipidemia, the man is taking amlodipine and following a low-calorie diet. Physical examination shows that the blood pressure is 129/89 mm Hg, the pulse rate is 78/min, the respiratory rate is 14/min, and the temperature is 36.6°C (98.0°F). His abdomen is lax with no tenderness or rigidity, and rectal examination shows no blood in the rectal vault. Cardiac auscultation reveals a 3/6 holosystolic murmur in the tricuspid area, which increases in intensity with inspiration. Altered metabolism of which of the following amino acids is most likely the explanation for this patient’s presentation?
Q195
A 5-year-old boy presents to a pediatric orthopedic surgeon for evaluation of spinal curvature. His primary care physician noticed during an annual checkup that the boy's shoulders were uneven, and radiograph revealed early onset scoliosis. His past medical history is significant for multiple fractures as well as short stature. Based on the early presentation of scoliosis and the unusual history of fractures, the surgeon orders further workup and discovers a genetic mutation in an extracellular protein. This protein exists in two different forms. The first is an insoluble dimer that is linked by disulfide bonds and links integrins to the extracellular matrix. The second is a soluble protein that assists with clotting. Based on these descriptions, which of the following proteins is most likely mutated in this patient?
Q196
A 7-day-old female newborn is brought to the physician because of lethargy, vomiting, poor feeding, and diarrhea for 4 days. She was born at 39 weeks' gestation. Vital signs are within normal limits. Bilateral cataracts and icterus are present. Examination shows jaundice of the skin, and the liver is palpated 5-cm below the right costal margin. Muscle tone is decreased in all extremities. Serum glucose concentration is 40 mg/dL. Which of the following metabolites is most likely to be increased in this patient?
Q197
An 18-month-old girl is brought to the pediatrician’s office for failure to thrive and developmental delay. The patient’s mother says she has not started speaking and is just now starting to pull herself up to standing position. Furthermore, her movement appears to be restricted. Physical examination reveals coarse facial features and restricted joint mobility. Laboratory studies show increased plasma levels of several enzymes. Which of the following is the underlying biochemical defect in this patient?
Q198
A 65-year-old male prisoner goes on a hunger strike to protest the conditions of his detainment. After 5 days without food, he suffers a seizure for which he is taken into a medical facility. On physical examination, he looks pale and diaphoretic. His blood glucose level is 50 mg/dL. In order to keep a constant supply of energy to his brain, which of the following molecules is his liver releasing into the bloodstream?
Q199
A 17-year-old girl is brought in by her mother due to rapid weight loss over the past month. The patient says she has been having episodes of diarrhea, which she attributes to laxatives she takes regularly to keep her weight down. She also says she has not had her period yet. The patient’s mother adds that the patient has been underperforming at school and acting very strangely at home. Her current BMI is 16.8 kg/m2. On physical examination, the skin on her limbs and around her neck is inflamed and erythematous. Her tongue is bright red and smooth. She states that over the last 2 weeks, she has been eating nothing but small portions of fruit. She is diagnosed with a vitamin deficiency. Which of the following statements is true about the vitamin most likely deficient in this patient?
Q200
A 7-month-old boy is brought in to his pediatrician’s office due to concern for recurrent infections. The parents state that over the last 3-4 months, the boy has had multiple viral respiratory infections, along with a fungal pneumonia requiring hospitalization. Currently he is without complaints; however, the parents are concerned that he continues to have loose stools and is falling off of his growth curve. Newborn screening is not recorded in the patient’s chart. On exam, the patient’s temperature is 98.4°F (36.9°C), blood pressure is 108/68 mmHg, pulse is 90/min, and respirations are 12/min. The patient is engaging appropriately and is able to grasp, sit, and is beginning to crawl. However, the patient is at the 20th percentile for length and weight, when he was previously at the 50th percentile at 3 months of age. Further screening suggests that the patient has an autosomal recessive immunodeficiency associated with absent T-cells. Which of the following is also associated with this disease?
Metabolism US Medical PG Practice Questions and MCQs
Question 191: A 25-year-old woman comes to the emergency department because of a mild headache, dizziness, fatigue, and nausea over the past several hours. She has no history of serious illness and takes no medications. She lives in a basement apartment and uses a wood stove for heating. Her temperature is 36°C (96.8°F) and pulse is 120/min. Arterial blood gas analysis shows a carboxyhemoglobin level of 11% (N = < 1.5). Which of the following mechanisms is the underlying cause of this patient's symptoms?
A. Formation of carboxyhemoglobin reducing oxygen transport capacity (Correct Answer)
B. Inhibition of hemoglobin synthesis in bone marrow
C. Direct cellular toxicity from carbon monoxide metabolites
D. Competitive inhibition of oxygen at tissue level
E. Decreased hemoglobin-oxygen binding affinity
Explanation: ***Formation of carboxyhemoglobin reducing oxygen transport capacity***
- Carbon monoxide binds to hemoglobin with **200-250 times greater affinity** than oxygen, forming **carboxyhemoglobin (COHb)**.
- This patient's **carboxyhemoglobin level of 11%** (normal <1.5%) confirms CO poisoning from the **wood stove** in her basement apartment.
- COHb formation **reduces oxygen-carrying capacity** of blood, leading to **tissue hypoxia** and symptoms of headache, dizziness, fatigue, and nausea.
- CO also **shifts the oxygen-hemoglobin dissociation curve leftward**, impairing oxygen release to tissues.
*Inhibition of hemoglobin synthesis in bone marrow*
- Carbon monoxide does **not** inhibit hemoglobin synthesis.
- This mechanism would be seen in conditions like **iron deficiency anemia**, **anemia of chronic disease**, or exposure to toxins like **lead**.
- CO poisoning is an **acute** problem of oxygen transport, not a chronic problem of hemoglobin production.
*Direct cellular toxicity from carbon monoxide metabolites*
- Carbon monoxide is **not significantly metabolized** in the human body.
- CO is eliminated unchanged through the **lungs** when the patient breathes fresh air or receives oxygen therapy.
- The toxicity is from **CO itself** binding to hemoglobin, myoglobin, and cytochrome enzymes, not from any metabolites.
*Competitive inhibition of oxygen at tissue level*
- While CO does bind to **myoglobin** and **mitochondrial cytochrome oxidase** at the tissue level, this is a **secondary mechanism**.
- The **primary and most significant mechanism** is carboxyhemoglobin formation, which reduces oxygen delivery to tissues.
- Tissue-level effects contribute to toxicity but don't explain the elevated **carboxyhemoglobin level** seen in this patient.
*Decreased hemoglobin-oxygen binding affinity*
- This is **incorrect**; CO actually causes hemoglobin to bind oxygen **more tightly**, not less.
- CO shifts the **oxygen-hemoglobin dissociation curve to the left**, increasing hemoglobin's affinity for oxygen and impairing oxygen release to tissues.
- The primary problem is **reduced oxygen-carrying capacity** from CO occupying hemoglobin binding sites, not decreased affinity.
Question 192: A 34-year-old woman presents to the emergency department with prominent hypotension and tachycardia. On examination, she has a low central venous pressure and high cardiac output. Her temperature is 38.9°C (102.0°F). The physician suspects a bacterial infection with a gram-negative bacterium. Samples are sent to the lab. Meanwhile, high volumes of fluids were given, but the blood pressure did not improve. She was started on noradrenaline. At the biochemical level, a major reaction was induced as part of this patient’s presentation. Of the following vitamins, which one is related to the coenzyme that participates in this induced biochemical reaction?
A. Vitamin B6 (pyridoxal phosphate)
B. Vitamin B2 (riboflavin)
C. Vitamin B1 (thiamine)
D. Vitamin B5 (pantothenic acid)
E. Vitamin B3 (niacin) (Correct Answer)
Explanation: ***Vitamin B3 (niacin)***
- The patient presents with **septic shock from gram-negative bacteria**, characterized by hypotension, high cardiac output, low CVP, and poor response to fluids.
- In septic shock, **inducible nitric oxide synthase (iNOS)** is massively upregulated in response to bacterial endotoxin (lipopolysaccharide).
- **iNOS produces excessive nitric oxide (NO)**, causing widespread vasodilation and refractory hypotension.
- The enzymatic activity of iNOS **requires NADPH as an essential cofactor** to donate electrons for the conversion of L-arginine to NO.
- **NADPH is derived from NAD+ and NADP+**, which require **Vitamin B3 (niacin)** as their precursor.
- This is the "major induced biochemical reaction" in septic shock—the massive NO production via iNOS that depends on niacin-derived cofactors.
*Vitamin B6 (pyridoxal phosphate)*
- Pyridoxal phosphate is a coenzyme for **amino acid metabolism** (transamination, decarboxylation, deamination).
- While important for protein metabolism, it is **not directly involved in iNOS activity** or the nitric oxide pathway central to septic shock pathophysiology.
*Vitamin B2 (riboflavin)*
- Riboflavin forms **FAD and FMN**, which are cofactors for **redox reactions** in the electron transport chain and other oxidative processes.
- Although involved in cellular respiration, **FAD/FMN are not the primary cofactors for iNOS** in septic shock.
*Vitamin B1 (thiamine)*
- Thiamine forms **thiamine pyrophosphate (TPP)**, a cofactor for **dehydrogenase enzymes** in glucose metabolism (pyruvate dehydrogenase, α-ketoglutarate dehydrogenase).
- While thiamine deficiency can worsen lactic acidosis in sepsis, **TPP is not involved in the iNOS/NO pathway** that causes vasodilatory shock.
*Vitamin B5 (pantothenic acid)*
- Pantothenic acid is a component of **coenzyme A (CoA)**, essential for fatty acid metabolism and the Krebs cycle.
- While metabolically important, **CoA is not a cofactor for iNOS** or the nitric oxide overproduction mechanism in septic shock.
Question 193: A 26-year-old man comes to the physician for evaluation of fatigue, facial rash, hair loss, and tingling of his hands and feet. He has followed a vegetarian diet for the past 3 years and has eaten 8 raw egg whites daily for the past year in preparation for a bodybuilding competition. Physical examination shows conjunctival injections and a scaly, erythematous rash around the eyes and mouth. Laboratory studies show decreased activity of propionyl-coenzyme A carboxylase in peripheral blood lymphocytes. Which of the following substances is most likely to be decreased in this patient?
A. Methylmalonyl-CoA (Correct Answer)
B. Cystathionine
C. Lactate
D. Adenine
E. Ribulose-5-phosphate
Explanation: ***Methylmalonyl-CoA***
- This patient has classic **biotin deficiency** due to consumption of raw egg whites. **Avidin** in raw egg whites binds biotin and prevents its absorption, leading to symptoms of dermatitis, alopecia, conjunctivitis, and neurological manifestations.
- Biotin is an essential cofactor for several carboxylase enzymes, including **propionyl-CoA carboxylase**, which catalyzes the conversion of **propionyl-CoA → methylmalonyl-CoA**.
- With **decreased propionyl-CoA carboxylase activity** (as stated in the question), the enzyme cannot efficiently convert its substrate to product. This results in **decreased formation of the product, methylmalonyl-CoA**.
- While propionyl-CoA (the substrate) would accumulate, methylmalonyl-CoA (the product) would be **decreased** due to impaired enzymatic conversion.
*Cystathionine*
- Cystathionine is an intermediate in the **transsulfuration pathway** (homocysteine → cysteine), which requires **vitamin B6** as a cofactor, not biotin.
- Its levels would not be directly affected by biotin deficiency or decreased propionyl-CoA carboxylase activity.
*Lactate*
- Lactate levels are elevated in conditions involving **anaerobic metabolism** or impaired mitochondrial function.
- Biotin deficiency can affect pyruvate carboxylase (another biotin-dependent enzyme), but this would not specifically decrease lactate levels. If anything, impaired pyruvate carboxylase might increase lactate by limiting pyruvate's entry into gluconeogenesis.
*Adenine*
- Adenine is a purine nucleobase involved in nucleotide synthesis and salvage pathways.
- Its metabolism is unrelated to biotin-dependent carboxylases and would not be affected in this patient.
*Ribulose-5-phosphate*
- Ribulose-5-phosphate is an intermediate in the **pentose phosphate pathway**, which generates NADPH and ribose-5-phosphate for nucleotide synthesis.
- This pathway is independent of biotin-dependent enzymes and would not be directly affected by propionyl-CoA carboxylase deficiency.
Question 194: A 55-year-old man is evaluated in the clinic for several episodes of diarrhea during the past 2 months. He denies having fever or abdominal pain and states that his diarrhea has been getting worse despite the use of over-the-counter loperamide and bismuth compounds. Upon further questioning, he recalls having multiple episodes of a burning sensation in his neck and upper chest, associated with redness and flushing of his face, which lasted for a few seconds. Because of his hypertension and dyslipidemia, the man is taking amlodipine and following a low-calorie diet. Physical examination shows that the blood pressure is 129/89 mm Hg, the pulse rate is 78/min, the respiratory rate is 14/min, and the temperature is 36.6°C (98.0°F). His abdomen is lax with no tenderness or rigidity, and rectal examination shows no blood in the rectal vault. Cardiac auscultation reveals a 3/6 holosystolic murmur in the tricuspid area, which increases in intensity with inspiration. Altered metabolism of which of the following amino acids is most likely the explanation for this patient’s presentation?
A. Arginine
B. Glycine
C. Tryptophan (Correct Answer)
D. Phenylalanine
E. Methionine
Explanation: **Tryptophan**
- The patient's symptoms of chronic diarrhea, flushing, and a tricuspid holosystolic murmur are highly suggestive of **carcinoid syndrome**, which is caused by the overproduction of **serotonin** from tryptophan.
- Tryptophan is the precursor amino acid for serotonin synthesis. In carcinoid syndrome, tumor cells (often neuroendocrine tumors) have an increased capacity to convert tryptophan into serotonin, bypassing normal regulatory mechanisms.
*Arginine*
- Arginine is a precursor for **nitric oxide (NO)** synthesis, which can cause flushing and vasodilation. However, it is not directly linked to the diarrheal and cardiac symptoms seen in carcinoid syndrome.
- While NO can contribute to some flushing syndromes, the overall clinical picture, especially the chronic diarrhea and valvular heart disease, is not explained by altered arginine metabolism.
*Glycine*
- Glycine is an inhibitory neurotransmitter and a component of many proteins, but it is not directly involved in the synthesis of vasoactive amines or hormones that cause flushing, diarrhea, or valvular heart disease.
- There is no known direct link between altered glycine metabolism and the specific constellation of symptoms presented by this patient.
*Phenylalanine*
- Phenylalanine is an essential amino acid and a precursor to tyrosine, which in turn is a precursor to catecholamines (dopamine, norepinephrine, epinephrine) and thyroid hormones.
- Disorders of phenylalanine metabolism, such as **phenylketonuria**, typically present with neurological symptoms and developmental delays, not carcinoid syndrome.
*Methionine*
- Methionine is an essential amino acid involved in various metabolic pathways, including the synthesis of cysteine and S-adenosylmethionine.
- Altered methionine metabolism is associated with conditions like **homocystinuria**, which involves cardiovascular and neurological issues but does not typically cause the classic symptoms of carcinoid syndrome.
Question 195: A 5-year-old boy presents to a pediatric orthopedic surgeon for evaluation of spinal curvature. His primary care physician noticed during an annual checkup that the boy's shoulders were uneven, and radiograph revealed early onset scoliosis. His past medical history is significant for multiple fractures as well as short stature. Based on the early presentation of scoliosis and the unusual history of fractures, the surgeon orders further workup and discovers a genetic mutation in an extracellular protein. This protein exists in two different forms. The first is an insoluble dimer that is linked by disulfide bonds and links integrins to the extracellular matrix. The second is a soluble protein that assists with clotting. Based on these descriptions, which of the following proteins is most likely mutated in this patient?
A. Type 1 collagen
B. Type 3 collagen
C. Fibronectin (Correct Answer)
D. Fibrillin
E. Elastin
Explanation: ***Fibronectin***
- **Fibronectin** uniquely exists in **two distinct forms**: an **insoluble dimeric form** (linked by disulfide bonds) in the extracellular matrix that binds **integrins** and connects them to matrix components, AND a **soluble plasma form** that participates in **blood clotting, wound healing, and opsonization**.
- This dual existence (insoluble ECM dimer + soluble plasma protein involved in clotting) is the **key distinguishing feature** that matches the biochemical description in the question.
- Fibronectin mutations can affect connective tissue integrity and skeletal development, though they are rare.
*Type 1 collagen*
- **Type 1 collagen** is the most abundant collagen, crucial for **bone, skin, tendons**, and ligaments. Mutations cause **osteogenesis imperfecta** with brittle bones, fractures, and short stature.
- While clinically this matches the patient's presentation, Type 1 collagen does **NOT exist as a soluble protein involved in clotting**, which is explicitly stated in the question stem.
- It forms insoluble triple-helix fibrils but lacks the soluble clotting form described.
*Type 3 collagen*
- **Type 3 collagen** is found in **distensible tissues** (blood vessels, intestines, skin). Mutations cause **Ehlers-Danlos syndrome type IV** with vascular fragility.
- It forms fibrillar structures in the ECM but does **NOT have a soluble form involved in blood clotting**.
- Does not match the dual-form requirement in the question.
*Fibrillin*
- **Fibrillin** is a major component of **microfibrils** in elastic fibers, providing structural support. Mutations cause **Marfan syndrome** (tall stature, arachnodactyly, cardiovascular issues).
- While it is an ECM component, fibrillin does **NOT exist as a soluble clotting protein**.
- Does not fulfill both biochemical criteria stated in the question.
*Elastin*
- **Elastin** provides **elasticity and resilience** to tissues (skin, blood vessels, lungs) and forms the core of elastic fibers.
- Elastin does **NOT link integrins to the ECM** in the manner described, nor does it have a **soluble form involved in clotting**.
- Does not match either key biochemical feature described.
Question 196: A 7-day-old female newborn is brought to the physician because of lethargy, vomiting, poor feeding, and diarrhea for 4 days. She was born at 39 weeks' gestation. Vital signs are within normal limits. Bilateral cataracts and icterus are present. Examination shows jaundice of the skin, and the liver is palpated 5-cm below the right costal margin. Muscle tone is decreased in all extremities. Serum glucose concentration is 40 mg/dL. Which of the following metabolites is most likely to be increased in this patient?
A. Branched-chain amino acids
B. Limit dextrins
C. Galactose-1-phosphate (Correct Answer)
D. Sphingomyelin
E. Uric acid
Explanation: ***Galactose-1-phosphate***
- The constellation of **neonatal lethargy, vomiting, poor feeding, diarrhea, jaundice, hepatomegaly, cataracts, decreased muscle tone**, and **hypoglycemia** in a 7-day-old newborn strongly points to **classic galactosemia**.
- In classic galactosemia, there is a deficiency of **galactose-1-phosphate uridyltransferase (GALT)**, leading to the accumulation of **galactose-1-phosphate** as well as galactitol and galactose.
*Branched-chain amino acids*
- Elevated **branched-chain amino acids** (leucine, isoleucine, valine) are characteristic of **maple syrup urine disease**.
- While maple syrup urine disease can present with lethargy, poor feeding, and neurologic symptoms, it does not typically cause **cataracts, jaundice**, or **hepatomegaly**.
*Limit dextrins*
- **Limit dextrins** are intermediate products of starch digestion and accumulated in glycogen storage diseases, particularly **Cori disease (Type III glycogen storage disease)** or **Anderson disease (Type IV glycogen storage disease)**.
- While glycogen storage diseases can cause **hypoglycemia** and **hepatomegaly**, they do not typically present with **cataracts, vomiting, diarrhea**, or prominent early onset jaundice like galactosemia.
*Sphingomyelin*
- Accumulation of **sphingomyelin** is characteristic of **Niemann-Pick disease**, a lysosomal storage disorder.
- While Niemann-Pick disease can present with hepatosplenomegaly and neurologic regression, it typically does not cause acute neonatal distress with **cataracts, acute jaundice**, or **vomiting and diarrhea** as seen here.
*Uric acid*
- Elevated **uric acid** is a hallmark of disorders such as **Lesch-Nyhan syndrome** or conditions causing increased purine breakdown or decreased excretion.
- Lesch-Nyhan syndrome presents with self-mutilation, hypotonia, and cognitive deficits, which do not align with the described symptoms. Hyperuricemia is not a feature of galactosemia.
Question 197: An 18-month-old girl is brought to the pediatrician’s office for failure to thrive and developmental delay. The patient’s mother says she has not started speaking and is just now starting to pull herself up to standing position. Furthermore, her movement appears to be restricted. Physical examination reveals coarse facial features and restricted joint mobility. Laboratory studies show increased plasma levels of several enzymes. Which of the following is the underlying biochemical defect in this patient?
A. Congenital lack of lysosomal formation
B. Inappropriate protein targeting to endoplasmic reticulum
C. Failure of mannose phosphorylation (Correct Answer)
D. Inappropriate degradation of lysosomal enzymes
E. Misfolding of nuclear proteins
Explanation: ***Failure of mannose phosphorylation***
- The constellation of **failure to thrive**, **developmental delay**, **coarse facial features**, restricted joint mobility, and elevated plasma enzymes in an 18-month-old girl is highly suggestive of **I-cell disease** (mucolipidosis type II).
- **I-cell disease** is caused by the deficiency of **N-acetylglucosaminyl-1-phosphotransferase**, an enzyme responsible for phosphorylating mannose residues on lysosomal enzymes, which is crucial for proper targeting to the lysosome.
*Congenital lack of lysosomal formation*
- **Lysosomes** are present in this condition, but their enzymes are misdirected.
- A congenital lack of lysosomal formation would present with even more severe and widespread cellular dysfunction, possibly incompatible with life beyond early embryonic stages.
*Inappropriate protein targeting to endoplasmic reticulum*
- Proteins destined for the endoplasmic reticulum (ER) are typically targeted by an N-terminal signal peptide and then processed within the ER.
- While ER dysfunction can cause various disorders, the specific symptoms and enzyme elevations point away from a primary ER targeting defect related to lysosomal enzymes.
*Inappropriate degradation of lysosomal enzymes*
- In I-cell disease, lysosomal enzymes are synthesized but are **not properly targeted to the lysosomes**; instead, they are secreted into the bloodstream, leading to their elevated plasma levels.
- While some degradation might occur, the primary issue is mis-packaging and secretion, not increased degradation within the cell.
*Misfolding of nuclear proteins*
- Misfolding of nuclear proteins can lead to a variety of genetic disorders and cellular stress responses, but the clinical presentation, particularly the accumulation of undegraded material and elevated plasma lysosomal enzymes, is not characteristic of primary nuclear protein misfolding.
- The pathology in I-cell disease centers on lysosomal dysfunction rather than nuclear protein abnormalities.
Question 198: A 65-year-old male prisoner goes on a hunger strike to protest the conditions of his detainment. After 5 days without food, he suffers a seizure for which he is taken into a medical facility. On physical examination, he looks pale and diaphoretic. His blood glucose level is 50 mg/dL. In order to keep a constant supply of energy to his brain, which of the following molecules is his liver releasing into the bloodstream?
A. Glycogen
B. Glucose-6-phosphate
C. ß-hydroxybutyric acid (Correct Answer)
D. Fatty acids
E. Glucose-1-phosphate
Explanation: ***ß-hydroxybutyric acid***
- After 5 days of a hunger strike, **glycogen stores** are depleted, forcing the body to rely on **fatty acid oxidation** and **ketone body production** in the liver as an alternative fuel source for the brain.
- **ß-hydroxybutyrate** is one of the primary ketone bodies released by the liver into the bloodstream to provide energy, especially for the brain, during prolonged fasting.
*Glycogen*
- **Glycogenolysis** (breakdown of glycogen) is a short-term response to low blood glucose and supplies glucose for only about 24-36 hours of fasting. After 5 days, **hepatic glycogen stores** would be largely depleted.
- The liver releases **free glucose** into the bloodstream, not intact glycogen, from glycogen breakdown.
*Glucose-6-phosphate*
- **Glucose-6-phosphate** is an intermediate in glycolysis and gluconeogenesis, but it is not directly released into the bloodstream by the liver.
- It must be converted to **free glucose** by glucose-6-phosphatase before it can exit the hepatocyte and enter circulation.
*Fatty acids*
- The liver takes up **fatty acids** from adipose tissue breakdown during prolonged fasting to convert them into **ketone bodies**.
- While fatty acids are a major energy source for other tissues, the **brain cannot directly utilize fatty acids** for energy due to the inability of long-chain fatty acids to cross the blood-brain barrier.
*Glucose-1-phosphate*
- **Glucose-1-phosphate** is an intermediate formed during the breakdown of glycogen (glycogenolysis).
- Like glucose-6-phosphate, it is not directly released into the bloodstream but is further metabolized within the hepatocyte, eventually leading to the release of **free glucose**.
Question 199: A 17-year-old girl is brought in by her mother due to rapid weight loss over the past month. The patient says she has been having episodes of diarrhea, which she attributes to laxatives she takes regularly to keep her weight down. She also says she has not had her period yet. The patient’s mother adds that the patient has been underperforming at school and acting very strangely at home. Her current BMI is 16.8 kg/m2. On physical examination, the skin on her limbs and around her neck is inflamed and erythematous. Her tongue is bright red and smooth. She states that over the last 2 weeks, she has been eating nothing but small portions of fruit. She is diagnosed with a vitamin deficiency. Which of the following statements is true about the vitamin most likely deficient in this patient?
A. It increases the GI absorption of iron
B. It is derived from tyrosine
C. Synthesis requires vitamin B2 and B6 (Correct Answer)
D. Synthesis requires vitamin B1 and B6
E. It is used to treat hypertension
Explanation: ***Synthesis requires vitamin B2 and B6***
- The patient's symptoms (diarrhea, dermatitis, dementia-like behavior, glossitis, and weight loss) are classic for **pellagra**, which is caused by a deficiency in **niacin (vitamin B3)**.
- The synthesis of **niacin** from **tryptophan** requires **pyridoxine (vitamin B6)** and **riboflavin (vitamin B2)** as cofactors.
*It increases the GI absorption of iron*
- **Vitamin C** (ascorbic acid) enhances the **gastrointestinal absorption of non-heme iron** by reducing ferric iron to its ferrous form.
- Niacin does not play a direct role in the absorption of iron.
*It is derived from tyrosine*
- **Tyrosine** is a precursor to several important compounds, including **catecholamines** (dopamine, norepinephrine, epinephrine) and **thyroid hormones**.
- **Niacin** is predominantly synthesized from the essential amino acid **tryptophan**.
*Synthesis requires vitamin B1 and B6*
- While **vitamin B6** is essential for niacin synthesis from tryptophan, **vitamin B1 (thiamine)** is not directly involved in this pathway.
- Thiamine's primary role is in carbohydrate metabolism.
*It is used to treat hypertension*
- While **niacin** can affect lipid profiles, it is **not commonly used as a primary treatment for hypertension**.
- **Niacin** is used, primarily in pharmacologic doses, to **lower LDL cholesterol** and **triglycerides** and **raise HDL cholesterol**, often in conjunction with other lipid-lowering agents.
Question 200: A 7-month-old boy is brought in to his pediatrician’s office due to concern for recurrent infections. The parents state that over the last 3-4 months, the boy has had multiple viral respiratory infections, along with a fungal pneumonia requiring hospitalization. Currently he is without complaints; however, the parents are concerned that he continues to have loose stools and is falling off of his growth curve. Newborn screening is not recorded in the patient’s chart. On exam, the patient’s temperature is 98.4°F (36.9°C), blood pressure is 108/68 mmHg, pulse is 90/min, and respirations are 12/min. The patient is engaging appropriately and is able to grasp, sit, and is beginning to crawl. However, the patient is at the 20th percentile for length and weight, when he was previously at the 50th percentile at 3 months of age. Further screening suggests that the patient has an autosomal recessive immunodeficiency associated with absent T-cells. Which of the following is also associated with this disease?
A. Accumulation of deoxyadenosine (Correct Answer)
B. Nonfunctional common gamma chain
C. Mutation in ATM DNA repair gene
D. Dysfunctional cell chemotaxis
E. Negative nitroblue-tetrazolium test
Explanation: ***Accumulation of deoxyadenosine***
- The patient's presentation with **recurrent viral and fungal infections**, **failure to thrive**, and **absent T-cells** despite normal developmental milestones points towards **severe combined immunodeficiency (SCID)**.
- One of the most common causes of autosomal recessive SCID is **adenosine deaminase (ADA) deficiency**, which leads to an accumulation of **deoxyadenosine** and its toxic metabolites, particularly in lymphocytes, causing their destruction.
*Nonfunctional common gamma chain*
- A **nonfunctional common gamma chain** is associated with **X-linked SCID**, which is the most common form of SCID. However, the question specifies an **autosomal recessive** immunodeficiency.
- This defect affects signaling for several **cytokine receptors**, leading to impaired T-cell and NK-cell development.
*Mutation in ATM DNA repair gene*
- A **mutation in the ATM DNA repair gene** is characteristic of **ataxia-telangiectasia**, a primary immunodeficiency.
- While it can cause recurrent infections due to **T-cell defects** and IgA deficiency, it typically presents with **ataxia**, oculocutaneous telangiectasias, and increased risk of malignancy, which are not mentioned here.
*Dysfunctional cell chemotaxis*
- **Dysfunctional cell chemotaxis** is associated with disorders like **Leukocyte Adhesion Deficiency (LAD)** or **Chédiak-Higashi syndrome**.
- These conditions primarily affect neutrophil function and lead to severe bacterial infections, rather than the prominent viral and fungal infections and T-cell absence seen in this case.
*Negative nitroblue-tetrazolium test*
- A **negative nitroblue-tetrazolium (NBT) test** is indicative of **chronic granulomatous disease (CGD)**, a phagocytic disorder.
- CGD is characterized by recurrent infections with catalase-positive organisms due to the inability of phagocytes to produce a **respiratory burst**, which is inconsistent with the patient's broad spectrum of infections and T-cell deficiency.