A 5-year-old boy is brought into your office by his mother. His father recently passed away, and his mother states she just lost her job. She has been unable to buy food regularly, and they have had to eat boiled and preserved vegetables. His mother denies that the boy has any prior medical conditions, but the patient states that his gums bleed when he brushes his teeth. On exam, the patient's vital signs are normal, but he appears malnourished. There is gum hypertrophy present on exam along with small, curled hairs over his head. CBC is significant for a Hgb of 9.5 g/dL with an MCV of 85. PT, aPTT, and bleeding time are all normal. What is the most likely cause?
Q72
An 82-year-old woman is brought to the emergency room after her neighbor saw her fall in the hallway. She lives alone and remarks that she has been feeling weak lately. Her diet consists of packaged foods and canned meats. Her temperature is 97.6°F (36.4°C), blood pressure is 133/83 mmHg, pulse is 95/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable for a weak, frail, and pale elderly woman. Laboratory studies are ordered as seen below.
Hemoglobin: 9.1 g/dL
Hematocrit: 30%
Leukocyte count: 6,700/mm^3 with normal differential
Platelet count: 199,500/mm^3
MCV: 110 fL
Which of the following is the most likely deficiency?
Q73
A graduate student at the biochemistry laboratory decides to research the different effects of vitamin deficiencies in mice by completely depriving the mice of one vitamin. The symptoms of this deficiency include posterior column and spinocerebellar tract demyelination, as well as hemolytic anemia. Further analysis is negative for megaloblastic anemia, hypersegmented neutrophils, and elevated serum methylmalonic acid. What characteristic of the vitamin is causing the symptoms in the mice?
Q74
A 25-year-old man presents to the emergency department with sudden-onset severe pain in the right shoulder that occurred when he threw a bowling ball 2 hours ago. He has a history of dislocations in both shoulders and subluxation of the right knee and left wrist. There is no history of fractures. On physical examination, the right arm is slightly abducted and externally rotated. An anterior bulge is seen near the shoulder joint. The neurovascular examination of the right arm shows no abnormalities. The skin examination shows multiple widened atrophic scars around the knees, elbows, and ankles. The skin of the neck and around the elbow can easily be extended up to 4 cm. The sclera is white. The remainder of the physical examination shows no abnormalities. A defect in which of the following proteins is the most likely cause of the findings in this patient?
Q75
A 24-year-old man comes to the physician with his wife because of difficulty conceiving during the past year. He emigrated from rural Romania 2 years ago and has a history of recurrent respiratory infections since childhood for which he has not sought treatment. Physical examination shows mild hepatomegaly and clubbing of the nail beds. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are increased. Microscopic analysis of centrifuged seminal fluid shows no sperm cells. This patient's condition is most likely caused by impaired function of a channel protein that normally opens in response to binding of which of the following?
Q76
A 20-year-old male is brought by ambulance to the emergency room in extremis. He is minimally conscious, hypotensive, and tachypneic, and his breath gives off a "fruity" odor. An arterial blood gas and metabolic panel show anion gap metabolic acidosis. This patient is most likely deficient in which of the following metabolic actions?
Q77
A 55-year-old man with alcoholic cirrhosis is admitted to the hospital for routine evaluation before liver transplantation. The physician asks the patient to stop eating 10 hours before surgery. Which of the following structures contributes directly to preventing fasting hypoglycemia by producing glucose in this patient?
Q78
After being warned by the locals not to consume the freshwater, a group of American backpackers set off on a week-long hike into a region of the Ecuadorean Amazon forest known for large gold mines. The group of hikers stopped near a small stream and used the water they filtered from the stream to make dinner. Within the next half hour, the hikers began to experience headaches, vertigo, visual disturbances, confusion, tachycardia, and altered levels of consciousness. Which of the following enzymes was most likely inhibited in this group of hikers?
Q79
A 38-year-old, working, first-time mother brings her 9-month-old male infant to the pediatrician for "wounds that simply won't heal" and bleeding gums. She exclaims, "I have been extra careful with him making sure to not let him get dirty, I boil his baby formula for 15 minutes each morning before I leave for work to give to the caregiver, and he has gotten all of his vaccinations." This infant is deficient in a molecule that is also an essential co-factor for which of the following reactions?
Q80
On a medical trip to Nicaragua, you observe a sweet odor in the cerumen of a 12-hour-old female newborn. Within 48 hours, the newborn develops ketonuria, poor feeding, and a sweet odor is also noticed in the urine. By 96 hours, the newborn is extremely lethargic and opisthotonus is observed. In order to prevent a coma and subsequent death, which of the following amino acids is one of those that should be withheld from this newborn's diet?
Metabolism US Medical PG Practice Questions and MCQs
Question 71: A 5-year-old boy is brought into your office by his mother. His father recently passed away, and his mother states she just lost her job. She has been unable to buy food regularly, and they have had to eat boiled and preserved vegetables. His mother denies that the boy has any prior medical conditions, but the patient states that his gums bleed when he brushes his teeth. On exam, the patient's vital signs are normal, but he appears malnourished. There is gum hypertrophy present on exam along with small, curled hairs over his head. CBC is significant for a Hgb of 9.5 g/dL with an MCV of 85. PT, aPTT, and bleeding time are all normal. What is the most likely cause?
A. Vitamin C deficiency (Correct Answer)
B. Vitamin K deficiency
C. Vitamin B3 deficiency
D. Vitamin B12 deficiency
E. Iron deficiency
Explanation: ***Vitamin C deficiency***
- The patient's history of **malnutrition**, consumption of only **boiled and preserved vegetables** (which deplete vitamin C), **bleeding gums**, and **curled hairs** ("corkscrew hairs") are classic signs of scurvy, caused by vitamin C deficiency.
- **Vitamin C** is essential for **collagen synthesis** and *antioxidant function*, and its deficiency leads to impaired wound healing, fragile capillaries, and anemia.
*Vitamin K deficiency*
- This deficiency primarily affects **blood clotting**, leading to increased PT/aPTT, but the patient's **PT, aPTT, and bleeding time are all normal**.
- While bleeding gums can occur, it's not typically associated with **curled hairs** or caused by a diet of boiled vegetables in this manner.
*Vitamin B3 deficiency*
- Also known as **niacin deficiency**, it causes pellagra, characterized by the "3 Ds": **dermatitis**, **diarrhea**, and **dementia**.
- These symptoms are not present in the patient, and bleeding gums or curled hairs are not typical manifestations of niacin deficiency.
*Vitamin B12 deficiency*
- This deficiency usually results in **macrocytic anemia** (high MCV), **neurological symptoms**, and **glossitis** (sore, smooth tongue).
- The patient has a **normal MCV** (85) and none of the characteristic neurological or oral findings of B12 deficiency.
*Iron deficiency*
- Iron deficiency leads to **microcytic anemia** (low MCV) and symptoms like **fatigue**, **pallor**, and **pica**.
- The patient has **normocytic anemia** (MCV 85), and while anemia is present, the specific constellation of bleeding gums and curled hairs is not characteristic of iron deficiency.
Question 72: An 82-year-old woman is brought to the emergency room after her neighbor saw her fall in the hallway. She lives alone and remarks that she has been feeling weak lately. Her diet consists of packaged foods and canned meats. Her temperature is 97.6°F (36.4°C), blood pressure is 133/83 mmHg, pulse is 95/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable for a weak, frail, and pale elderly woman. Laboratory studies are ordered as seen below.
Hemoglobin: 9.1 g/dL
Hematocrit: 30%
Leukocyte count: 6,700/mm^3 with normal differential
Platelet count: 199,500/mm^3
MCV: 110 fL
Which of the following is the most likely deficiency?
A. Zinc
B. Vitamin B12
C. Thiamine
D. Niacin
E. Folate (Correct Answer)
Explanation: ***Folate***
- The patient's **macrocytic anemia** (MCV 110 fL, hemoglobin 9.1 g/dL) combined with a diet of **packaged foods and canned meats** with **no fresh fruits or vegetables** strongly suggests folate deficiency.
- **Folate is found exclusively in fresh produce** (leafy greens, fruits, legumes), which is completely absent from this patient's diet.
- **Elderly individuals** living alone with inadequate nutrition are at particularly high risk for **folate deficiency**.
*Vitamin B12*
- While vitamin B12 deficiency also causes **macrocytic anemia**, her diet includes **canned meats which retain B12** (heat-stable vitamin).
- B12 deficiency typically requires years to develop due to large hepatic stores, and often presents with **neurological manifestations** (subacute combined degeneration, peripheral neuropathy), which are absent here.
- The dietary pattern makes folate deficiency more likely than B12 deficiency.
*Zinc*
- Zinc deficiency causes impaired immune function, delayed wound healing, skin lesions, and **taste disturbances**, but **not macrocytic anemia**.
- No clinical or laboratory findings suggest zinc deficiency.
*Thiamine*
- Thiamine (vitamin B1) deficiency causes **Wernicke-Korsakoff syndrome** or **beriberi** (wet or dry), presenting with neurological symptoms, heart failure, or peripheral neuropathy.
- Thiamine deficiency does **not cause macrocytic anemia**.
*Niacin*
- Niacin (vitamin B3) deficiency causes **pellagra**, characterized by the \"3 D's\": **dermatitis, diarrhea, and dementia**.
- Niacin deficiency is **not associated with macrocytic anemia**.
Question 73: A graduate student at the biochemistry laboratory decides to research the different effects of vitamin deficiencies in mice by completely depriving the mice of one vitamin. The symptoms of this deficiency include posterior column and spinocerebellar tract demyelination, as well as hemolytic anemia. Further analysis is negative for megaloblastic anemia, hypersegmented neutrophils, and elevated serum methylmalonic acid. What characteristic of the vitamin is causing the symptoms in the mice?
A. The vitamin is important in rod and cone cells for vision
B. Deficiency causes the impaired production of blood clotting factors in the liver
C. The vitamin facilitates iron absorption
D. The vitamin controls serum calcium levels
E. The vitamin acts as a major antioxidant protecting cell membranes from oxidative damage (Correct Answer)
Explanation: ***The vitamin acts as a major antioxidant protecting cell membranes from oxidative damage***
- The symptoms of **posterior column and spinocerebellar tract demyelination** and **hemolytic anemia** are classic signs of **vitamin E deficiency**.
- **Vitamin E** is a **major lipid-soluble antioxidant** that protects cell membranes (including those in neurons and red blood cells) from **oxidative damage** by free radicals.
*The vitamin is important in rod and cone cells for vision*
- This statement describes the function of **vitamin A**, which is crucial for the synthesis of **rhodopsin** in rod cells and **iodopsin** in cone cells.
- **Vitamin A deficiency** typically causes **night blindness** and **xerophthalmia**, not demyelination or hemolytic anemia.
*Deficiency causes the impaired production of blood clotting factors in the liver*
- This describes **vitamin K deficiency**, which leads to a coagulopathy due to its role in the **gamma-carboxylation** of clotting factors **II, VII, IX, and X** in the liver.
- **Vitamin K deficiency** presents with **bleeding tendencies**, not neurological symptoms or hemolytic anemia.
*The vitamin facilitates iron absorption*
- This describes **vitamin C (ascorbic acid)**, which enhances **non-heme iron absorption** by reducing ferric iron (Fe3+) to ferrous iron (Fe2+).
- **Vitamin C deficiency** causes **scurvy**, characterized by **gingivitis**, **petechiae**, and impaired wound healing, not the symptoms listed.
*The vitamin controls serum calcium levels*
- This function is primarily attributed to **vitamin D**, which plays a critical role in **calcium and phosphate homeostasis** by regulating their absorption from the gut and reabsorption from the kidneys.
- **Vitamin D deficiency** causes **rickets** in children and **osteomalacia** in adults, primarily affecting bone health.
Question 74: A 25-year-old man presents to the emergency department with sudden-onset severe pain in the right shoulder that occurred when he threw a bowling ball 2 hours ago. He has a history of dislocations in both shoulders and subluxation of the right knee and left wrist. There is no history of fractures. On physical examination, the right arm is slightly abducted and externally rotated. An anterior bulge is seen near the shoulder joint. The neurovascular examination of the right arm shows no abnormalities. The skin examination shows multiple widened atrophic scars around the knees, elbows, and ankles. The skin of the neck and around the elbow can easily be extended up to 4 cm. The sclera is white. The remainder of the physical examination shows no abnormalities. A defect in which of the following proteins is the most likely cause of the findings in this patient?
A. Collagen (Correct Answer)
B. Keratin
C. Fibrillin-1
D. Tau
E. Elastin
Explanation: ***Collagen***
- This patient's symptoms, including **recurrent dislocations**, easy **skin extensibility**, and **atrophic scars**, are classic signs of **Ehlers-Danlos syndrome (EDS)**, which is primarily caused by defects in **collagen synthesis or processing**.
- The shoulder dislocation from a minor activity (throwing a bowling ball), along with multisystem hypermobility (shoulders, knee, wrist), strongly points to a **connective tissue disorder** affecting collagen.
*Keratin*
- **Keratin** is a structural protein primarily found in **epithelial cells**, forming hair, skin, and nails.
- Defects in keratin typically manifest as disorders of **skin fragility**, such as **epidermolysis bullosa**, not joint hypermobility or tissue extensibility.
*Fibrillin-1*
- **Fibrillin-1** defects cause **Marfan syndrome**, characterized by **tall stature**, **arachnodactyly**, **aortic root dilation**, and **lens dislocation**.
- While Marfan syndrome involves connective tissue, the patient's presentation of easy skin extensibility and atrophic scars is not characteristic of fibrillin-1 defects, and there is no mention of cardiovascular or ocular issues typical of Marfan.
*Tau*
- **Tau protein** is a **microtubule-associated protein** primarily found in neurons and is involved in stabilizing microtubules.
- Defects or abnormal aggregation of tau protein are associated with **neurodegenerative diseases** like **Alzheimer's disease** and **frontotemporal dementia**, not connective tissue disorders.
*Elastin*
- **Elastin** provides elasticity to tissues, allowing them to stretch and recoil. Defects can lead to conditions like **cutis laxa** or **Williams syndrome**.
- While some features of increased skin extensibility might overlap, the constellation of recurrent joint dislocations and specific atrophic scars seen in this patient is more indicative of **collagen defects** common in Ehlers-Danlos syndrome.
Question 75: A 24-year-old man comes to the physician with his wife because of difficulty conceiving during the past year. He emigrated from rural Romania 2 years ago and has a history of recurrent respiratory infections since childhood for which he has not sought treatment. Physical examination shows mild hepatomegaly and clubbing of the nail beds. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are increased. Microscopic analysis of centrifuged seminal fluid shows no sperm cells. This patient's condition is most likely caused by impaired function of a channel protein that normally opens in response to binding of which of the following?
A. Cyclic guanosine monophosphate
B. γ-aminobutyric acid
C. Cyclic adenosine monophosphate (cAMP) (Correct Answer)
D. N-methyl-D-aspartate
E. Dynein
Explanation: ***Cyclic adenosine monophosphate (cAMP)***
- This patient presents with **infertility** (azoospermia), **recurrent respiratory infections**, **hepatomegaly**, and **elevated liver enzymes**, which are highly suggestive of **cystic fibrosis**.
- **Cystic fibrosis** is caused by mutations in the **CFTR gene**, which encodes a **chloride channel protein** that is activated by **cAMP-dependent protein kinase A phosphorylation**.
*Cyclic guanosine monophosphate*
- **Cyclic GMP (cGMP)** is involved in the activation of certain **ion channels**, notably in **phototransduction** and the regulation of **vascular tone** via nitric oxide signaling.
- It does not directly regulate the chloride channels implicated in cystic fibrosis.
*γ-aminobutyric acid*
- **GABA** is the primary **inhibitory neurotransmitter** in the central nervous system, acting on **ligand-gated chloride channels** (GABA-A receptors) and G-protein coupled receptors (GABA-B receptors).
- Its function is unrelated to the **CFTR chloride channel** or the pathophysiology of cystic fibrosis.
*N-methyl-D-aspartate*
- **NMDA receptors** are a type of **glutamate receptor** that are **ligand-gated ion channels** permeable to calcium, sodium, and potassium, crucial for synaptic plasticity and learning.
- They are not involved in the function of the **CFTR protein** or the manifestations of cystic fibrosis.
*Dynein*
- **Dynein** is a **motor protein** responsible for the movement of **cilia and flagella**, and defects in dynein are associated with **primary ciliary dyskinesia (PCD)**.
- While PCD can cause recurrent respiratory infections and infertility due to immotile sperm, the hepatomegaly and elevated liver enzymes point more strongly towards **cystic fibrosis**, where the defect is in a **channel protein** regulated by cAMP, not a motor protein.
Question 76: A 20-year-old male is brought by ambulance to the emergency room in extremis. He is minimally conscious, hypotensive, and tachypneic, and his breath gives off a "fruity" odor. An arterial blood gas and metabolic panel show anion gap metabolic acidosis. This patient is most likely deficient in which of the following metabolic actions?
A. Glucagon production
B. Cortisol secretion
C. Formation of ketone bodies
D. Glucose production
E. Cellular uptake of glucose (Correct Answer)
Explanation: ***Cellular uptake of glucose***
- The patient's symptoms, including **fruity odor breath**, **anion gap metabolic acidosis**, and being found in extremis, are classic signs of **diabetic ketoacidosis (DKA)**.
- DKA results from a profound lack of **insulin**, which is essential for cells (especially muscle and adipose tissue) to take up glucose from the bloodstream, leading to hyperglycemia and a shift to fat metabolism.
*Glucagon production*
- **Glucagon** is a counter-regulatory hormone that *raises* blood glucose levels, and its production is often *increased* in DKA as the body attempts to provide fuel to cells in the absence of insulin's effect.
- A deficiency in glucagon production would more likely lead to **hypoglycemia**, not the profound hyperglycemia seen in DKA.
*Cortisol secretion*
- **Cortisol** is another counter-regulatory hormone that *increases* blood glucose, and its secretion is typically *elevated* in stress states like DKA.
- A deficiency in cortisol (e.g., in adrenal insufficiency) would present with different symptoms such as **hypoglycemia**, **hyponatremia**, and **hyperkalemia**, without the classic DKA picture.
*Formation of ketone bodies*
- The patient's **fruity odor breath** and **anion gap metabolic acidosis** are direct consequences of the *overproduction* of **ketone bodies**.
- This overproduction occurs when the body, lacking glucose for fuel due to insulin deficiency, switches to **fat metabolism**, leading to excessive formation of acetoacetate, beta-hydroxybutyrate, and acetone.
*Glucose production*
- **Glucose production** (gluconeogenesis and glycogenolysis) is typically *increased* in DKA as the liver tries to supply glucose to the body due to perceived cellular starvation (despite high blood glucose).
- A deficiency in glucose production, such as in certain glycogen storage diseases or severe liver failure, would lead to **hypoglycemia**, not the hyperglycemia characteristic of DKA.
Question 77: A 55-year-old man with alcoholic cirrhosis is admitted to the hospital for routine evaluation before liver transplantation. The physician asks the patient to stop eating 10 hours before surgery. Which of the following structures contributes directly to preventing fasting hypoglycemia by producing glucose in this patient?
A. Adrenal cortex
B. Skeletal muscle
C. Red blood cells
D. Skin
E. Intestine (Correct Answer)
Explanation: ***Correct: Intestine***
- The **intestine** (particularly the small intestine) possesses the enzymatic machinery for **gluconeogenesis**, including glucose-6-phosphatase, allowing it to directly produce and release free glucose into the bloodstream.
- During prolonged fasting (>10 hours), intestinal gluconeogenesis can contribute up to **20-25% of total glucose production**, utilizing substrates like glutamine and glycerol.
- In patients with **alcoholic cirrhosis**, hepatic gluconeogenesis is impaired, making extrahepatic sites like the intestine and kidneys increasingly important for maintaining euglycemia.
- The intestine directly produces glucose and releases it into the portal circulation, making it a direct contributor to preventing fasting hypoglycemia.
*Incorrect: Skeletal muscle*
- **Skeletal muscle lacks glucose-6-phosphatase**, the enzyme required to convert glucose-6-phosphate to free glucose for release into the bloodstream.
- Muscle undergoes proteolysis during fasting, releasing amino acids (particularly alanine and glutamine) that serve as gluconeogenic substrates for the liver and kidneys.
- This represents an **indirect contribution** to glucose homeostasis through substrate provision, not direct glucose production.
*Incorrect: Red blood cells*
- **Red blood cells** lack mitochondria and can only perform anaerobic glycolysis, producing lactate.
- Lactate from RBCs can be recycled to glucose in the liver via the **Cori cycle**, but RBCs themselves are net glucose consumers, not producers.
- They contribute indirectly through substrate provision, not direct glucose synthesis.
*Incorrect: Skin*
- The **skin** has no significant role in glucose production or gluconeogenesis.
- Its primary functions are protection, thermoregulation, and sensation; it does not possess the enzymatic capacity for gluconeogenesis.
- Skin does not contribute to maintaining blood glucose homeostasis during fasting.
*Incorrect: Adrenal cortex*
- The **adrenal cortex** secretes hormones (cortisol, aldosterone) that regulate glucose metabolism indirectly.
- **Cortisol** promotes hepatic and renal gluconeogenesis and decreases peripheral glucose utilization, but the adrenal gland itself does not synthesize or release glucose.
- This is a regulatory role, not direct glucose production.
Question 78: After being warned by the locals not to consume the freshwater, a group of American backpackers set off on a week-long hike into a region of the Ecuadorean Amazon forest known for large gold mines. The group of hikers stopped near a small stream and used the water they filtered from the stream to make dinner. Within the next half hour, the hikers began to experience headaches, vertigo, visual disturbances, confusion, tachycardia, and altered levels of consciousness. Which of the following enzymes was most likely inhibited in this group of hikers?
A. NADH dehydrogenase
B. ATP synthase
C. Cytochrome c oxidase (Correct Answer)
D. Cytochrome bc1 complex
E. Succinate dehydrogenase
Explanation: ***Cytochrome c oxidase***
- The symptoms described (headaches, vertigo, visual disturbances, confusion, tachycardia, altered consciousness occurring within 30 minutes) are characteristic of **acute cyanide poisoning**.
- **Cyanide** is commonly found in water near **gold mining operations**, where it is used in the gold extraction process and can contaminate local water sources.
- **Cyanide** is a potent inhibitor of **cytochrome c oxidase** (Complex IV) in the electron transport chain, binding to the heme iron (Fe³⁺) and preventing oxygen utilization, leading to **histotoxic hypoxia**.
- This results in cellular energy failure, particularly affecting high-energy-demand organs like the brain and heart, explaining the acute neurological and cardiovascular symptoms.
*NADH dehydrogenase*
- While NADH dehydrogenase (Complex I) is a component of the electron transport chain, it is not the primary target of **cyanide poisoning**.
- Inhibitors of Complex I include rotenone and barbiturates, which cause different clinical presentations and do not produce the rapid onset of symptoms seen with cyanide.
*ATP synthase*
- **ATP synthase** (Complex V) synthesizes ATP using the proton gradient, but it is not directly inhibited by **cyanide**.
- Inhibitors of ATP synthase, such as oligomycin, prevent ATP synthesis by blocking the enzyme directly, whereas cyanide acts upstream at Complex IV.
*Cytochrome bc1 complex*
- The **cytochrome bc1 complex** (Complex III) is involved in electron transfer and proton pumping, but it is not the primary enzyme inhibited by **cyanide**.
- Inhibitors of Complex III include antimycin A, which would disrupt the electron transport chain but do not cause the characteristic rapid-onset symptoms of cyanide poisoning.
*Succinate dehydrogenase*
- **Succinate dehydrogenase** (Complex II) participates in both the citric acid cycle and the electron transport chain, but it is not targeted by **cyanide**.
- Inhibitors of Complex II, such as malonate, competitively block succinate oxidation but do not produce the acute systemic toxicity characteristic of cyanide poisoning.
Question 79: A 38-year-old, working, first-time mother brings her 9-month-old male infant to the pediatrician for "wounds that simply won't heal" and bleeding gums. She exclaims, "I have been extra careful with him making sure to not let him get dirty, I boil his baby formula for 15 minutes each morning before I leave for work to give to the caregiver, and he has gotten all of his vaccinations." This infant is deficient in a molecule that is also an essential co-factor for which of the following reactions?
A. Conversion of homocysteine to methionine
B. Conversion of alpha ketoglutarate to succinyl-CoA
C. Conversion of dopamine to norepinephrine (Correct Answer)
D. Conversion of pyruvate to acetyl-CoA
E. Conversion of pyruvate to oxaloacetate
Explanation: ***Conversion of dopamine to norepinephrine***
- The infant's symptoms of "wounds that simply won't heal" and **bleeding gums** are classic signs of **scurvy**, caused by a deficiency in **vitamin C (ascorbic acid)**.
- **Vitamin C** is an essential cofactor for **dopamine beta-hydroxylase**, the enzyme responsible for converting **dopamine to norepinephrine**.
*Conversion of homocysteine to methionine*
- This reaction is catalyzed by **methionine synthase**, which requires **vitamin B12** (cobalamin) and **folate (vitamin B9)** as cofactors.
- Deficiency in these vitamins would lead to **megaloblastic anemia** and neurological symptoms, not delayed wound healing and bleeding gums.
*Conversion of alpha ketoglutarate to succinyl-CoA*
- This step in the **Krebs cycle** is catalyzed by **alpha-ketoglutarate dehydrogenase**, which requires **thiamine (vitamin B1)**, **lipoic acid**, **Mg2+**, **NAD+**, and **FAD** as cofactors.
- Thiamine deficiency can cause **beriberi** or **Wernicke-Korsakoff syndrome**, not scurvy symptoms.
*Conversion of pyruvate to acetyl-CoA*
- This reaction is catalyzed by the **pyruvate dehydrogenase complex**, which requires **thiamine (vitamin B1)**, **lipoic acid**, **coenzyme A**, **FAD**, and **NAD+** as cofactors.
- A deficiency in any of these, particularly thiamine, leads to impaired carbohydrate metabolism and lactic acidosis.
*Conversion of pyruvate to oxaloacetate*
- This reaction is catalyzed by **pyruvate carboxylase**, which requires **biotin (vitamin B7)** as a cofactor and is essential for **gluconeogenesis**.
- Biotin deficiency is rare and can present with dermatitis, hair loss, and neurological symptoms, not the classic signs of scurvy.
Question 80: On a medical trip to Nicaragua, you observe a sweet odor in the cerumen of a 12-hour-old female newborn. Within 48 hours, the newborn develops ketonuria, poor feeding, and a sweet odor is also noticed in the urine. By 96 hours, the newborn is extremely lethargic and opisthotonus is observed. In order to prevent a coma and subsequent death, which of the following amino acids is one of those that should be withheld from this newborn's diet?
A. Methionine
B. Valine (Correct Answer)
C. Phenylalanine
D. Threonine
E. Tyrosine
Explanation: ***Valine***
- The clinical presentation with a **sweet odor in cerumen** and urine, followed by **ketonuria**, poor feeding, lethargy, and opisthotonus, is highly characteristic of **Maple Syrup Urine Disease (MSUD)**.
- MSUD is an autosomal recessive disorder caused by a deficiency in the **branched-chain alpha-keto acid dehydrogenase complex (BCKDC)**, which is responsible for the metabolism of the branched-chain amino acids (BCAAs): **leucine, isoleucine, and valine**. Therefore, restricting these amino acids from the diet is crucial.
*Methionine*
- **Methionine** is an essential amino acid, but its dietary restriction is primarily associated with conditions like **homocystinuria**, not MSUD.
- The deficiency in MSUD specifically impacts the branched-chain amino acid pathway, not the methionine metabolism pathway.
*Phenylalanine*
- **Phenylalanine** is restricted in the diet of individuals with **phenylketonuria (PKU)**, a different inborn error of metabolism.
- PKU is characterized by the inability to metabolize phenylalanine to tyrosine, leading to its accumulation and neurotoxicity, with different clinical features than described.
*Threonine*
- **Threonine** is a different essential amino acid and is not one of the branched-chain amino acids whose catabolism is impaired in MSUD.
- Restricting threonine would not directly address the metabolic defect seen in MSUD.
*Tyrosine*
- **Tyrosine** is a non-essential amino acid that becomes essential in conditions like **phenylketonuria (PKU)**, where it cannot be synthesized from phenylalanine.
- It is not directly implicated in the pathogenesis or dietary management of MSUD.
