A 2-month-old boy is brought to his pediatrician’s office to be evaluated for new onset seizures and poor weight gain. The patient’s father says he is unable to track with his eyes and is unresponsive to verbal stimuli. The patient is hypotonic on physical exam. Further studies show elevated serum lactate levels and elevated levels of alanine and pyruvate. Family history reveals that several distant family members suffered from neurological diseases and died of unknown causes at a young age. Which of the following amino acids should be increased in this patient’s diet?
Q92
An experimental compound added to a protein disrupts both alpha helices as well as beta-pleated sheets. Which of the following has the experimental compound affected?
Q93
A 32-year-old woman comes to the emergency department because of a 5-day history of anxiety, irritability, insomnia, and abdominal pain that began after a weekend of partying. She also reports “bloody” urine as well as a tingling sensation in her hands and feet. She has never experienced similar symptoms. She does not smoke but says that she tends to drink too much (5 or more drinks) when partying with friends. Her temperature is 37°C (98.6°F), pulse is 123/min, and blood pressure is 124/70 mm Hg. Examination shows slightly decreased power in the shoulders (3/5) and thighs (4/5), along with hyporeflexia. Urine dipstick shows:
Blood Negative
Protein Negative
WBC Negative
Bilirubin Negative
Urobilinogen 3+
This patient's condition is most likely caused by a defect in which of the following enzymes?
Q94
A 56-year-old woman visits her primary care provider complaining of fatigue, weight gain, increased thirst, hair loss, and headaches. She has been perimenopausal for 3 years. She was diagnosed with rheumatoid arthritis 4 years ago and prescribed oral prednisolone. Currently, she takes prednisolone and omeprazole daily. Her vital signs are as follows: blood pressure 150/90 mm Hg, heart rate 70/min, respiratory rate 13/min, and temperature 36.6°C (97.9°F). Her weight is 95 kg (209.4 lb), height is 165 cm (5 ft 4 in), BMI is 34.9 kg/m2, waist circumference is 109 cm (42.9 in), and hip circumference is 93 cm (36.6 in). At physical exam, the patient has abdominal obesity, round red face, and increased fat deposition on the back and around the neck. Her skin elasticity is diminished. Cardiac auscultation reveals fixed splitting of S2 with an increased aortic component. The rest of the exam is unremarkable. Blood analysis shows the following findings:
Total serum cholesterol 204.9 mg/dL
HDL 50.3 mg/dL
LDL 131.4 mg/dL
Triglycerides 235.9 mg/dL
Fasting serum glucose 192.0 mg/dL
Which of the following options describes the pathogenesis of the patient’s hyperglycemia?
Q95
A 55-year-old woman presents with acute onset abdominal pain radiating to her back, nausea, and vomiting. CT scan suggests a diagnosis of acute pancreatitis. The pathogenesis of acute pancreatitis relates to inappropriate activation of trypsinogen to trypsin. Which of the following activates trypsin in normal digestion?
Q96
A 6-day-old newborn girl is brought into the hospital by her mother because of excessive vomiting and poor feeding. The mother did not have antenatal care. Her temperature is 36.8°C (98.2°F), blood pressure is 50/30 mm Hg, and pulse is 150/min. On examination, the infant is dehydrated and demonstrates signs of shock. Her genitalia are ambiguous, with fused labia and an enlarged clitoris. Laboratory results are shown:
Serum sodium (Na) 125 mEq/L
Serum potassium (K) 6 mEq/L
Serum 17-hydroxyprogesterone 100,000 ng/dL (normal level is 1,000–3,000 ng/dL)
Which of the following is the most likely cause of this infant's condition?
Q97
A 49-year-old man presents to the clinic with skin lesions and chronic diarrhea. His wife also reports that he has become more irritable and forgetful in the past year. His medical history is significant for a gastroenterostomy performed 4 years ago due to gastric outlet obstruction caused by hyperplastic polyposis, which was complicated by afferent loop syndrome. He became a vegan a year ago, and currently, his diet consists of starchy foods such as potatoes, corn, and leafy vegetables. The patient’s vital signs include blood pressure 100/75 mm Hg, heart rate 55/min, respiratory rate 14/min, and temperature 36.3℃ (97.3℉). His skin is pale, dry, and thin, with areas of desquamation and redness on the sun-exposed areas. His lymph nodes are not enlarged and breath sounds are normal. The cardiac apex beat is located in the 5th left intercostal space 2 cm lateral to the midclavicular line. Heart sounds are diminished and S3 is present. His abdomen is slightly distended and nontender to palpation. The liver and spleen are not enlarged. Neurologic examination reveals symmetrical hypesthesia for all types of sensation in both upper and lower extremities in a 'gloves and socks' distribution. On a mini-mental status examination, the patient scores 25 out of 30. Production of which substance is most likely to be impaired in this patient?
Q98
A 26-year-old medical student who is preparing for Step 1 exams is woken up by her friend for breakfast. She realizes that she must have fallen asleep at her desk while attempting to study through the night. While walking with her friend to breakfast, she realizes that she has not eaten since breakfast the previous day. Using this as motivation to review some biochemistry, she pauses to consider what organs are responsible for allowing her to continue thinking clearly in this physiologic state. Which of the following sets of organs are associated with the major source of energy currently facilitating her cognition?
Q99
An 11-year-old girl presents to her primary care physician because she has been having difficulty hearing her teachers at school. She says that the difficulty hearing started about a year ago, and it has slowly been getting worse. Her past medical history is significant for multiple fractures in both her upper and lower extremities. She also recently had a growth spurt and says that her friends say she is tall and lanky. A mutation in which of the following genes is most likely associated with this patient's condition?
Q100
A 38-year-old woman presents to the clinic complaining of fatigue and recurrent stomach pain for the past 3 years. She reports an intermittent, dull ache at the epigastric region that is not correlated with food intake. Antacids seem to help a little, but the patient still feels uncomfortable during the episodes. She reports that she has been getting increasingly tired over the past week. The patient denies fevers, chills, nausea, vomiting, melena, hematochezia, or diarrhea but does endorse intermittent abdominal bloating. Her past medical history is significant for type 1 diabetes that is currently managed with an insulin pump. Physical examination demonstrates pale conjunctiva and mild abdominal tenderness at the epigastric region. Laboratory studies are shown below:
Leukocyte count: 7,800/mm^3
Segmented neutrophils: 58%
Bands: 4%
Eosinophils: 2%
Basophils: 0%
Lymphocytes: 29%
Monocytes: 7%
Hemoglobin: 10 g/dL
Platelet count: 170,000/mm^3
Mean corpuscular hemoglobin concentration: 36 g/dL
Mean corpuscular volume: 103 µm^3
Homocysteine: 15 mmol/L (Normal = 4.0 – 10.0 mmol/L)
Methylmalonic acid: 0.6 umol/L (Normal = 0.00 – 0.40 umol/L)
What substance would you expect to be decreased in this patient?
Metabolism US Medical PG Practice Questions and MCQs
Question 91: A 2-month-old boy is brought to his pediatrician’s office to be evaluated for new onset seizures and poor weight gain. The patient’s father says he is unable to track with his eyes and is unresponsive to verbal stimuli. The patient is hypotonic on physical exam. Further studies show elevated serum lactate levels and elevated levels of alanine and pyruvate. Family history reveals that several distant family members suffered from neurological diseases and died of unknown causes at a young age. Which of the following amino acids should be increased in this patient’s diet?
A. Isoleucine
B. Valine
C. Arginine (Correct Answer)
D. Leucine
E. Methionine
Explanation: ***Arginine***
- The symptoms of **seizures, developmental delay, hypotonia, and elevated lactate/pyruvate** levels, along with a family history of early deaths, are highly suggestive of a **mitochondrial disorder**, specifically **pyruvate dehydrogenase complex (PDC) deficiency**.
- **Arginine** supplementation is used in certain **mitochondrial disorders** to enhance **nitric oxide (NO) production**, which improves **endothelial function and tissue perfusion**. While the primary treatment for PDC deficiency is a **ketogenic diet** and cofactor supplementation (thiamine, lipoic acid), among the amino acid options listed, arginine has supportive evidence in mitochondrial cytopathies.
- Arginine may help counteract **endothelial dysfunction** and improve oxygen delivery to tissues affected by mitochondrial impairment.
*Isoleucine*
- **Isoleucine** is a **branched-chain amino acid (BCAA)** that is catabolized to produce acetyl-CoA and succinyl-CoA for energy.
- In **PDC deficiency**, the problem is the conversion of **pyruvate to acetyl-CoA**, not BCAA metabolism. Increasing BCAAs is not a therapeutic strategy for this condition.
- Excessive BCAA intake could potentially worsen metabolic imbalances without addressing the underlying enzymatic defect.
*Valine*
- **Valine** is another **branched-chain amino acid (BCAA)** with no specific role in managing PDC deficiency.
- Like isoleucine, valine supplementation does not address the **pyruvate dehydrogenase complex defect** and is not part of standard dietary management.
- BCAAs require careful monitoring in metabolic disorders and are not indicated for mitochondrial disorders like PDC deficiency.
*Leucine*
- **Leucine** is a **branched-chain amino acid (BCAA)** and potent activator of mTOR signaling for protein synthesis.
- Direct leucine supplementation is **not indicated for PDC deficiency** and does not address the metabolic block at the pyruvate dehydrogenase step.
- In disorders like **maple syrup urine disease (MSUD)**, BCAAs including leucine must be **restricted**, not supplemented.
*Methionine*
- **Methionine** is a sulfur-containing amino acid important for **methylation reactions** through S-adenosylmethionine (SAM) synthesis.
- There is **no established role** for methionine supplementation in **pyruvate dehydrogenase complex deficiency** or mitochondrial disorders presenting with lactic acidosis.
- Methionine metabolism is not directly related to the pathophysiology of PDC deficiency.
Question 92: An experimental compound added to a protein disrupts both alpha helices as well as beta-pleated sheets. Which of the following has the experimental compound affected?
A. Ionic bonds between amino acids
B. Hydrogen bonds between amino acids (Correct Answer)
C. Covalent peptide bonds between amino acids
D. Disulfide bonds between amino acids
E. The primary structure of the protein
Explanation: ***Hydrogen bonds between amino acids***
- Both **alpha helices** and **beta-pleated sheets** are formed and stabilized by **hydrogen bonds** between the backbone atoms (carbonyl oxygen and amide hydrogen) of different amino acids.
- Disrupting these specific bonds would destabilize and unravel these **secondary protein structures**.
*Ionic bonds between amino acids*
- **Ionic bonds** are electrostatic interactions between charged R-groups of amino acids and primarily contribute to **tertiary** and **quaternary protein structures**.
- While important for overall protein folding, they are not the primary stabilizing force for **alpha helices** and **beta-pleated sheets**.
*Covalent peptide bonds between amino acids*
- **Peptide bonds** are the **covalent links** that form the **primary structure** (amino acid sequence) of a protein.
- Disrupting these would lead to the protein breaking down into smaller peptides or individual amino acids, which is a much more severe disruption than just affecting secondary structures.
*Disulfide bonds between amino acids*
- **Disulfide bonds** are **covalent bonds** formed between the sulfur atoms of two **cysteine residues**.
- These bonds contribute significantly to the stability of **tertiary protein structure** and sometimes **quaternary structure**, but not directly to the formation of alpha helices or beta-pleated sheets.
*The primary structure of the protein*
- The **primary structure** is the unique linear sequence of amino acids linked by **peptide bonds**.
- Disruption of **alpha helices** and **beta-pleated sheets** indicates an effect on the **secondary structure**, not the primary sequence itself.
Question 93: A 32-year-old woman comes to the emergency department because of a 5-day history of anxiety, irritability, insomnia, and abdominal pain that began after a weekend of partying. She also reports “bloody” urine as well as a tingling sensation in her hands and feet. She has never experienced similar symptoms. She does not smoke but says that she tends to drink too much (5 or more drinks) when partying with friends. Her temperature is 37°C (98.6°F), pulse is 123/min, and blood pressure is 124/70 mm Hg. Examination shows slightly decreased power in the shoulders (3/5) and thighs (4/5), along with hyporeflexia. Urine dipstick shows:
Blood Negative
Protein Negative
WBC Negative
Bilirubin Negative
Urobilinogen 3+
This patient's condition is most likely caused by a defect in which of the following enzymes?
A. Homogentisic acid dioxygenase
B. Uroporphyrinogen decarboxylase
C. Ferrochelatase
D. Porphobilinogen deaminase (Correct Answer)
E. Aminolevulinic acid synthase
Explanation: ***Porphobilinogen deaminase***
- This enzyme deficiency leads to **acute intermittent porphyria (AIP)**, characterized by **neuropsychiatric symptoms** (anxiety, irritability, insomnia), **neuropathy** (tingling, muscle weakness, hyporeflexia), and abdominal pain.
- The patient's **"bloody" urine with negative blood on dipstick** suggests porphobilinogen/porphyrin accumulation, which causes urine to appear dark red or port-wine colored—a classic finding in AIP.
- **Alcohol is a known trigger** for acute AIP attacks, fitting the patient's history of heavy drinking during partying.
- Diagnosis is confirmed by elevated urinary **porphobilinogen (PBG)** and **aminolevulinic acid (ALA)** during acute attacks.
*Homogentisic acid dioxygenase*
- A defect in this enzyme causes **alkaptonuria**, leading to black urine upon standing and eventually **ochronosis** (darkening of cartilage and connective tissue) and arthropathy.
- It does not present with acute neuropsychiatric or neuropathic symptoms.
*Uroporphyrinogen decarboxylase*
- Deficiency in this enzyme causes **porphyria cutanea tarda (PCT)**, which primarily manifests with **photosensitivity**, blistering skin lesions, and hyperpigmentation.
- While it is a porphyria, it does not typically cause the acute neurological or psychological symptoms seen in this patient.
*Ferrochelatase*
- A deficiency in ferrochelatase causes **erythropoietic protoporphyria (EPP)**, leading to **photosensitive skin reactions** and potential liver damage.
- It does not present with the acute neuropsychiatric and neuropathic symptoms described.
*Aminolevulinic acid synthase*
- While **aminolevulinic acid synthase (ALAS)** is the rate-limiting enzyme in heme synthesis, its *deficiency* would lead to a reduction in heme, causing **sideroblastic anemia**, not acute porphyria.
- *Increased* activity of ALAS can contribute to porphyria pathogenesis, but the enzyme itself is not the defective one in AIP.
Question 94: A 56-year-old woman visits her primary care provider complaining of fatigue, weight gain, increased thirst, hair loss, and headaches. She has been perimenopausal for 3 years. She was diagnosed with rheumatoid arthritis 4 years ago and prescribed oral prednisolone. Currently, she takes prednisolone and omeprazole daily. Her vital signs are as follows: blood pressure 150/90 mm Hg, heart rate 70/min, respiratory rate 13/min, and temperature 36.6°C (97.9°F). Her weight is 95 kg (209.4 lb), height is 165 cm (5 ft 4 in), BMI is 34.9 kg/m2, waist circumference is 109 cm (42.9 in), and hip circumference is 93 cm (36.6 in). At physical exam, the patient has abdominal obesity, round red face, and increased fat deposition on the back and around the neck. Her skin elasticity is diminished. Cardiac auscultation reveals fixed splitting of S2 with an increased aortic component. The rest of the exam is unremarkable. Blood analysis shows the following findings:
Total serum cholesterol 204.9 mg/dL
HDL 50.3 mg/dL
LDL 131.4 mg/dL
Triglycerides 235.9 mg/dL
Fasting serum glucose 192.0 mg/dL
Which of the following options describes the pathogenesis of the patient’s hyperglycemia?
A. Glucocorticoids bind to surface receptors of the glomerular endothelial cells and inhibit filtration of glucose.
B. Glucocorticoids activate surface membrane sodium channels in the islet beta-cells, which leads to Na+ influx and inhibition of insulin synthesis.
C. Binding of glucocorticoids to surface G-protein-coupled corticosteroid receptors leads to activation of the inositol-3-phosphate pathway and consequent transcription of gluconeogenic enzymes.
D. Upon activation of intracellular corticosteroid receptors in hepatocytes, its DNA-binding domain binds to glucocorticoid response elements and triggers transcription of gluconeogenic enzymes. (Correct Answer)
E. Extensive gluconeogenic enzyme transcription is activated by glucocorticoids via the cAMP pathway.
Explanation: ***Upon activation of intracellular corticosteroid receptors in hepatocytes, its DNA-binding domain binds to glucocorticoid response elements and triggers transcription of gluconeogenic enzymes.***
- This option accurately describes the **genomic mechanism** of glucocorticoid action, where activated intracellular receptors translocate to the nucleus and bind to **glucocorticoid response elements (GREs)** on DNA.
- This binding directly upregulates the transcription of genes encoding **gluconeogenic enzymes** in the liver, leading to increased hepatic glucose production and hyperglycemia.
*Glucocorticoids bind to surface receptors of the glomerular endothelial cells and inhibit filtration of glucose.*
- Glucocorticoids do not generally bind to surface receptors of glomerular endothelial cells to inhibit glucose filtration. **Glucose filtration** is primarily determined by glomerular permeability and renal threshold, not by direct glucocorticoid effects on filtration.
- While glucocorticoids can affect kidney function, their primary mechanism for causing hyperglycemia is not through altered glomerular glucose filtration.
*Glucocorticoids activate surface membrane sodium channels in the islet beta-cells, which leads to Na+ influx and inhibition of insulin synthesis.*
- Glucocorticoids primarily **impair insulin sensitivity** in peripheral tissues and increase hepatic glucose output; they do not typically act by activating surface membrane sodium channels in beta-cells.
- The main mechanism of glucocorticoid-induced beta-cell dysfunction is associated with increased oxidative stress and endoplasmic reticulum stress, not direct Na+ channel activation leading to insulin synthesis inhibition.
*Binding of glucocorticoids to surface G-protein-coupled corticosteroid receptors leads to activation of the inositol-3-phosphate pathway and consequent transcription of gluconeogenic enzymes.*
- Glucocorticoid receptors are **intracellular (nuclear) receptors**, not G-protein-coupled receptors on the cell surface. They act genomically by binding to DNA.
- While some rapid, non-genomic effects of glucocorticoids exist, the primary and sustained hyperglycemic effect is mediated through genomic pathways involving intracellular receptors and GREs.
*Extensive gluconeogenic enzyme transcription is activated by glucocorticoids via the cAMP pathway.*
- Glucocorticoids primarily modulate gene expression directly through **intracellular receptors** binding to GREs, not predominantly via the cAMP pathway.
- The **cAMP pathway** is more commonly associated with hormones like glucagon and catecholamines in regulating gluconeogenesis.
Question 95: A 55-year-old woman presents with acute onset abdominal pain radiating to her back, nausea, and vomiting. CT scan suggests a diagnosis of acute pancreatitis. The pathogenesis of acute pancreatitis relates to inappropriate activation of trypsinogen to trypsin. Which of the following activates trypsin in normal digestion?
A. Secretin
B. Lipase
C. Cholecystokinin
D. Enterokinase (Correct Answer)
E. Amylase
Explanation: ***Enterokinase***
- **Enterokinase** (also known as enteropeptidase) is a brush border enzyme of the duodenum that specifically cleaves and activates pancreatic **trypsinogen** into its active form, **trypsin**.
- Once activated, **trypsin** then activates other pancreatic proteases (e.g., chymotrypsinogen, procarboxypeptidases, proelastase) within the intestinal lumen.
*Secretin*
- **Secretin** is a hormone released by S cells in the duodenum in response to acidic chyme and acts on the pancreas to stimulate the secretion of **bicarbonate-rich fluid**, which neutralizes gastric acid.
- It does not directly activate digestive enzymes like trypsinogen.
*Lipase*
- **Lipase** is a pancreatic enzyme secreted in its active form that breaks down **dietary fats** (triglycerides) into fatty acids and monoglycerides.
- It plays no role in the activation of trypsinogen.
*Cholecystokinin*
- **Cholecystokinin (CCK)** is a hormone released by I cells in the duodenum in response to fats and proteins, stimulating the contraction of the **gallbladder** and the secretion of **pancreatic enzymes**.
- While it promotes the release of pancreatic enzymes, it does not directly activate trypsinogen.
*Amylase*
- **Amylase** is a pancreatic enzyme secreted in its active form that breaks down **complex carbohydrates** (starches) into simpler sugars (disaccharides and oligosaccharides).
- It is not involved in the activation cascade of pancreatic proteases.
Question 96: A 6-day-old newborn girl is brought into the hospital by her mother because of excessive vomiting and poor feeding. The mother did not have antenatal care. Her temperature is 36.8°C (98.2°F), blood pressure is 50/30 mm Hg, and pulse is 150/min. On examination, the infant is dehydrated and demonstrates signs of shock. Her genitalia are ambiguous, with fused labia and an enlarged clitoris. Laboratory results are shown:
Serum sodium (Na) 125 mEq/L
Serum potassium (K) 6 mEq/L
Serum 17-hydroxyprogesterone 100,000 ng/dL (normal level is 1,000–3,000 ng/dL)
Which of the following is the most likely cause of this infant's condition?
A. Deficiency of 21-hydroxylase (Correct Answer)
B. Deficiency of 11-beta-hydroxylase
C. Deficiency of 5-alpha reductase
D. Deficiency of placental aromatase
E. Deficiency of 17-alpha-hydroxylase
Explanation: ***Deficiency of 21-hydroxylase***
- The combination of **salt-wasting crisis** (hyponatremia, hyperkalemia, hypotension, shock) in a newborn with **ambiguous genitalia** (virilization in a female) and a dramatically elevated **17-hydroxyprogesterone** level is pathognomonic for **21-hydroxylase deficiency**.
- This enzyme defect prevents the synthesis of **cortisol** and **aldosterone**, leading to an accumulation of steroid precursors like 17-hydroxyprogesterone, which are then shunted towards **androgen production**.
*Deficiency of 11-beta-hydroxylase*
- This deficiency causes accumulation of **11-deoxycorticosterone (DOC)**, a mineralocorticoid, leading to **hypertension** and **hypokalemia**, not the salt-wasting crisis seen here.
- While it also causes virilization from increased androgens, the **electrolyte imbalance pattern** is distinct.
*Deficiency of 5-alpha reductase*
- This condition affects **males (XY individuals)**, presenting with **undermasculinized external genitalia** (ambiguous at birth, virilize at puberty).
- It does not cause **adrenal insufficiency** or **salt-wasting symptoms** in either sex.
*Deficiency of placental aromatase*
- This is a rare autosomal recessive disorder where the placenta cannot convert fetal androgens into estrogens, leading to **virilization of the mother** and **female fetus**.
- There are no associated **electrolyte abnormalities** or **adrenal crisis symptoms** as seen in this infant.
*Deficiency of 17-alpha-hydroxylase*
- This deficiency impairs the synthesis of **cortisol** and **sex steroids**, but **mineralocorticoid production (aldosterone and DOC)** is increased.
- Patients typically present with **hypertension**, **hypokalemia**, and **sexual infantilism** (lack of secondary sex characteristics), not virilization or salt-wasting.
Question 97: A 49-year-old man presents to the clinic with skin lesions and chronic diarrhea. His wife also reports that he has become more irritable and forgetful in the past year. His medical history is significant for a gastroenterostomy performed 4 years ago due to gastric outlet obstruction caused by hyperplastic polyposis, which was complicated by afferent loop syndrome. He became a vegan a year ago, and currently, his diet consists of starchy foods such as potatoes, corn, and leafy vegetables. The patient’s vital signs include blood pressure 100/75 mm Hg, heart rate 55/min, respiratory rate 14/min, and temperature 36.3℃ (97.3℉). His skin is pale, dry, and thin, with areas of desquamation and redness on the sun-exposed areas. His lymph nodes are not enlarged and breath sounds are normal. The cardiac apex beat is located in the 5th left intercostal space 2 cm lateral to the midclavicular line. Heart sounds are diminished and S3 is present. His abdomen is slightly distended and nontender to palpation. The liver and spleen are not enlarged. Neurologic examination reveals symmetrical hypesthesia for all types of sensation in both upper and lower extremities in a 'gloves and socks' distribution. On a mini-mental status examination, the patient scores 25 out of 30. Production of which substance is most likely to be impaired in this patient?
A. Flavin mononucleotide
B. NAD+ (Correct Answer)
C. Coenzyme Q10
D. Biotin
E. Menaquinone
Explanation: ***NAD+***
- This patient presents with symptoms consistent with **pellagra**, a deficiency of **niacin (vitamin B3)**, characterized by the 3 D's: **dermatitis**, **diarrhea**, and **dementia (or neuropsychiatric symptoms like irritability and forgetfulness)**. NAD+ (nicotinamide adenine dinucleotide) is a coenzyme derived from niacin that is crucial for numerous metabolic processes.
- The patient's history of **gastroenterostomy** and a diet primarily of **starchy foods** (low in tryptophan, a niacin precursor) further increase the risk of niacin deficiency.
*Flavin mononucleotide*
- **Flavin mononucleotide (FMN)** is derived from **riboflavin (vitamin B2)**. Riboflavin deficiency can cause angular stomatitis, cheilosis, glossitis, and seborrheic dermatitis, which are not the primary symptoms here.
- While some skin findings might overlap, the prominent **diarrhea**, **dementia**, and distinct rash on sun-exposed areas point away from riboflavin deficiency.
*Coenzyme Q10*
- **Coenzyme Q10 (ubiquinone)** is not typically associated with a deficiency syndrome presenting with the classic "3 D's" of pellagra. It's involved in mitochondrial electron transport.
- While CoQ10 deficiency can cause myopathy and neurological issues, it does not typically manifest with the specific combination of **dermatitis and diarrhea** seen in this patient.
*Biotin*
- **Biotin (vitamin B7)** deficiency can lead to dermatitis, hair loss (alopecia), and neurological symptoms, but it typically does not present with the severe **gastrointestinal and neuropsychiatric symptoms** in the same classic "3 D's" pattern as niacin deficiency.
- Prolonged antibiotic use or consumption of raw egg whites (avidin) are common causes of biotin deficiency, which are not mentioned in this case.
*Menaquinone*
- **Menaquinone (vitamin K2)** is a form of vitamin K. Vitamin K deficiency primarily impacts **blood clotting**, leading to easy bruising and bleeding.
- It plays no direct role in the metabolic pathways linked to the skin, gastrointestinal, and neurological symptoms observed in this patient.
Question 98: A 26-year-old medical student who is preparing for Step 1 exams is woken up by her friend for breakfast. She realizes that she must have fallen asleep at her desk while attempting to study through the night. While walking with her friend to breakfast, she realizes that she has not eaten since breakfast the previous day. Using this as motivation to review some biochemistry, she pauses to consider what organs are responsible for allowing her to continue thinking clearly in this physiologic state. Which of the following sets of organs are associated with the major source of energy currently facilitating her cognition?
A. Muscle only
B. Liver and kidney (Correct Answer)
C. Liver and muscle
D. Liver, muscle, and kidney
E. Liver only
Explanation: ***Liver and kidney***
- After an overnight fast (~16-24 hours without food), the **liver** is the **primary organ** responsible for maintaining blood glucose levels through **glycogenolysis** (initially) and **gluconeogenesis** (predominantly at this stage).
- The **kidney** also contributes to **gluconeogenesis** even during an overnight fast, providing approximately **10-15% of total glucose production**. While this contribution is relatively minor compared to the liver, it becomes increasingly important during more prolonged fasting states (>48-72 hours), where it can account for up to 40% of glucose production.
- Since the brain relies almost exclusively on glucose at this stage of fasting (ketone bodies are not yet a major fuel source), both organs that produce glucose for systemic use are correctly identified here.
*Muscle only*
- Muscle glycogen can only be used by the **muscle cells themselves** due to the absence of **glucose-6-phosphatase**, so muscle cannot release free glucose into the bloodstream for use by the brain.
- While muscle does provide amino acids (particularly alanine and glutamine) for gluconeogenesis in the liver and kidney, it does not directly supply glucose to support brain function.
*Liver and muscle*
- As explained above, muscle cannot directly supply glucose to the bloodstream to support brain function due to the lack of **glucose-6-phosphatase**.
- The liver is a major contributor, but muscle is not a direct source of blood glucose.
*Liver, muscle, and kidney*
- This option incorrectly includes muscle as a direct source of glucose for the brain. While liver and kidney both perform gluconeogenesis and release glucose into the bloodstream, muscle lacks this capability.
*Liver only*
- While the liver is indeed the **dominant source** of glucose during an overnight fast (contributing ~85-90% of gluconeogenesis), the **kidney also actively participates** in glucose production, contributing ~10-15% at this stage.
- Since the question asks which organs are "responsible" for maintaining cognition, and both organs contribute to systemic glucose production (even if disproportionately), "liver only" is incomplete.
- The kidney's contribution, though relatively minor during overnight fasting, becomes more substantial during prolonged fasting states.
Question 99: An 11-year-old girl presents to her primary care physician because she has been having difficulty hearing her teachers at school. She says that the difficulty hearing started about a year ago, and it has slowly been getting worse. Her past medical history is significant for multiple fractures in both her upper and lower extremities. She also recently had a growth spurt and says that her friends say she is tall and lanky. A mutation in which of the following genes is most likely associated with this patient's condition?
A. Type 4 collagen
B. Type 3 collagen
C. Fibrillin
D. Type 1 collagen (Correct Answer)
E. Fibroblast growth factor receptor
Explanation: ***Type 1 collagen***
- This patient's symptoms—hearing difficulty, multiple fractures, and tall/lanky stature—are classic signs of **osteogenesis imperfecta (OI)**, a genetic disorder caused by mutations in genes encoding **Type I collagen**.
- **Type I collagen** is a major component of bone, so defects lead to fragile bones and susceptibility to fractures, and it also plays a role in the structure of the ear, affecting hearing.
*Type 4 collagen*
- Mutations in **Type 4 collagen** are primarily associated with **Alport syndrome**, which classically presents with **hematuria**, progressive renal failure, and hearing loss.
- While hearing loss is present, the patient's other key symptoms of **multiple fractures** and **tall, lanky stature** are not characteristic of Alport syndrome.
*Type 3 collagen*
- Defects in **Type 3 collagen** are linked to **Ehlers-Danlos syndrome, vascular type**, which is characterized by fragile blood vessels, organs, and skin, leading to easy bruising, arterial rupture, and bowel perforation.
- While Type 3 collagen is found in connective tissues, its primary clinical manifestations do not align with the patient's presentation of recurrent fractures and hearing loss.
*Fibrillin*
- Mutations in **fibrillin-1** are responsible for **Marfan syndrome**, which presents with tall stature, long limbs (**arachnodactyly**), and cardiovascular issues like aortic dilation.
- While tall stature is observed, the patient's primary complaints of **recurrent fractures** and hearing loss are not typical features of Marfan syndrome.
*Fibroblast growth factor receptor*
- Mutations in **fibroblast growth factor receptor 3 (FGFR3)** are most commonly associated with **achondroplasia**, a form of dwarfism characterized by short stature, short limbs, and a large head.
- This is inconsistent with the patient's **tall and lanky stature** and does not account for the recurrent fractures or hearing difficulties.
Question 100: A 38-year-old woman presents to the clinic complaining of fatigue and recurrent stomach pain for the past 3 years. She reports an intermittent, dull ache at the epigastric region that is not correlated with food intake. Antacids seem to help a little, but the patient still feels uncomfortable during the episodes. She reports that she has been getting increasingly tired over the past week. The patient denies fevers, chills, nausea, vomiting, melena, hematochezia, or diarrhea but does endorse intermittent abdominal bloating. Her past medical history is significant for type 1 diabetes that is currently managed with an insulin pump. Physical examination demonstrates pale conjunctiva and mild abdominal tenderness at the epigastric region. Laboratory studies are shown below:
Leukocyte count: 7,800/mm^3
Segmented neutrophils: 58%
Bands: 4%
Eosinophils: 2%
Basophils: 0%
Lymphocytes: 29%
Monocytes: 7%
Hemoglobin: 10 g/dL
Platelet count: 170,000/mm^3
Mean corpuscular hemoglobin concentration: 36 g/dL
Mean corpuscular volume: 103 µm^3
Homocysteine: 15 mmol/L (Normal = 4.0 – 10.0 mmol/L)
Methylmalonic acid: 0.6 umol/L (Normal = 0.00 – 0.40 umol/L)
What substance would you expect to be decreased in this patient?
A. Lipase
B. Gastrin
C. Helicobacter pylori
D. Intrinsic factor (Correct Answer)
E. Lactase
Explanation: ***Intrinsic factor***
- The patient presents with **fatigue**, **pale conjunctiva**, and **macrocytic anemia** (Hgb 10 g/dL, MCV 103 µm^3), along with elevated **homocysteine** and **methylmalonic acid (MMA)**, which are classic signs of **vitamin B12 deficiency**.
- **Intrinsic factor** is essential for vitamin B12 absorption in the terminal ileum. Its decrease or absence, often due to **autoimmune atrophic gastritis** (a known association with type 1 diabetes), would directly lead to the observed deficiency.
*Lipase*
- **Lipase** is an enzyme involved in fat digestion, and its decrease is typically associated with **pancreatic insufficiency**.
- The patient's symptoms are not indicative of malabsorption of fats (e.g., steatorrhea), making decreased lipase unlikely to be the primary issue.
*Gastrin*
- **Gastrin** is a hormone that stimulates gastric acid secretion. In **atrophic gastritis** (which causes intrinsic factor deficiency), gastrin levels are typically **elevated (hypergastrinemia)** due to loss of negative feedback from reduced acid production.
- This option is incorrect because gastrin would be **increased**, not decreased, in the setting of pernicious anemia with atrophic gastritis.
*Helicobacter pylori*
- While **Helicobacter pylori** infection is a common cause of gastritis and can sometimes lead to peptic ulcers, the patient's symptoms (particularly the macrocytic anemia and elevated MMA) are more directly indicative of **vitamin B12 deficiency** due to an intrinsic factor issue.
- **H. pylori** itself is an infectious organism, not a substance expected to be decreased in the context of this B12 deficiency presentation.
*Lactase*
- **Lactase** is an enzyme that digests lactose. A decrease in lactase would lead to **lactose intolerance**, presenting with symptoms such as bloating, abdominal pain, and diarrhea after consuming dairy products.
- The patient's symptoms do not align with lactose intolerance, and there is no evidence to suggest lactase deficiency as the underlying cause of her macrocytic anemia.
