Integration with TCA cycle US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Integration with TCA cycle. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Integration with TCA cycle US Medical PG Question 1: An investigator is studying severely ill patients who experience hypoglycemia and ketonuria during times of fasting. The investigator determines that during these episodes, amino acids liberated from muscle proteins are metabolized to serve as substrates for gluconeogenesis. Nitrogen from this process is transported to the liver primarily in the form of which of the following molecules?
- A. Glutamate
- B. α-ketoglutarate
- C. Alanine (Correct Answer)
- D. Arginine
- E. Pyruvate
Integration with TCA cycle Explanation: ***Alanine***
- During prolonged fasting, **muscle proteins are catabolized** to provide amino acids for gluconeogenesis in the liver.
- **Alanine** is the primary amino acid released from muscle into the bloodstream to transport nitrogen to the liver through the **glucose-alanine cycle (Cahill cycle)**.
- In this cycle, pyruvate in muscle accepts an amino group from glutamate to form alanine, which is then transported to the liver, where it is deaminated back to pyruvate (for gluconeogenesis) and ammonia (for the urea cycle).
- **Glutamine** also serves as an important nitrogen transporter, particularly to the kidneys and intestines.
*Glutamate*
- **Glutamate** is an important amino acid in nitrogen metabolism within tissues, but it is not the primary form in which nitrogen is transported from muscle to the liver in significant quantities.
- While glutamate participates in transamination reactions within muscle, its efflux from muscle into the blood is less prominent than alanine for inter-organ nitrogen transport.
*α-ketoglutarate*
- **α-ketoglutarate** is a key intermediate in the **Krebs cycle** and accepts an amino group to form glutamate.
- It is an alpha-keto acid, not an amino acid, and therefore does not directly transport nitrogen in the form of an amino group to the liver via the bloodstream.
*Arginine*
- **Arginine** is primarily involved in the **urea cycle** within the liver, where it helps in the detoxification of ammonia, but it is not a major transporter of nitrogen from peripheral tissues to the liver for gluconeogenesis.
- Its role is mainly within the liver for urea synthesis, not for inter-organ nitrogen transport in this context.
*Pyruvate*
- **Pyruvate** is a keto acid that can be converted to alanine via transamination.
- While pyruvate is a precursor to alanine and a substrate for gluconeogenesis, it transports carbon skeletons and not nitrogen itself; **alanine is the actual nitrogen carrier** in this cycle.
Integration with TCA cycle US Medical PG Question 2: A 26-year-old African American man comes to the physician because of a 3-day history of fatigue, back pain, and dark urine. One week ago, he developed a headache and was treated with aspirin. He does not smoke or use illicit drugs. Physical examination shows conjunctival pallor. A peripheral blood smear shows erythrocytes with inclusions of denatured hemoglobin. Which of the following enzymes is involved in providing precursors for nucleotide synthesis in this patient?
- A. Glucose-6-phosphatase
- B. Carbamoyl phosphate synthetase I
- C. Pyruvate carboxylase
- D. Transaldolase (Correct Answer)
- E. Enolase
Integration with TCA cycle Explanation: ***Transaldolase***
- This patient likely has **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, indicated by fatigue, dark urine (hemolysis), and **Heinz bodies** (erythrocytes with inclusions of denatured hemoglobin) after aspirin exposure, which is an **oxidative stressor**.
- **Transaldolase** is an enzyme in the **non-oxidative phase of the pentose phosphate pathway (PPP)**, which produces **ribose-5-phosphate**, a precursor for nucleotide synthesis.
*Glucose-6-phosphatase*
- **Glucose-6-phosphatase** is involved in **gluconeogenesis** and glycogenolysis, primarily in the liver and kidneys, to release free glucose into the bloodstream.
- Deficiency leads to **Von Gierke disease**, characterized by hypoglycemia, hepatomegaly, lactic acidosis, and hyperlipidemia, which are not described here.
*Carbamoyl phosphate synthetase I*
- **Carbamoyl phosphate synthetase I (CPS I)** is a mitochondrial enzyme that catalyzes the first committed step in the **urea cycle**, converting ammonia and bicarbonate into carbamoyl phosphate.
- Its deficiency causes **hyperammonemia**, not hemolytic anemia or issues with nucleotide synthesis.
*Pyruvate carboxylase*
- **Pyruvate carboxylase** is a mitochondrial enzyme that converts **pyruvate to oxaloacetate**, a crucial step in **gluconeogenesis** and replenishing intermediates of the citric acid cycle.
- Deficiency can lead to lactic acidosis and hypoglycemia, which are not the primary symptoms here.
*Enolase*
- **Enolase** is an enzyme in **glycolysis** that catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate.
- It is not directly involved in providing precursors for nucleotide synthesis.
Integration with TCA cycle US Medical PG Question 3: A 3-week old boy is brought to the physician for the evaluation of lethargy, recurrent vomiting, and poor weight gain since birth. Physical examination shows decreased skin turgor and a bulging frontal fontanelle. Serum studies show an ammonia concentration of 170 μmol/L (N < 30) and low serum citrulline levels. The oral intake of which of the following nutrients should be restricted in this patient?
- A. Gluten
- B. Lactose
- C. Fructose
- D. Protein (Correct Answer)
- E. Vitamin A
Integration with TCA cycle Explanation: ***Protein***
- Elevated **ammonia** and low **citrulline** levels indicate a **urea cycle disorder**, which impairs the body's ability to excrete nitrogenous waste from protein metabolism.
- Restricting **protein intake** limits the production of ammonia, thereby reducing the toxic burden on the system and preventing further neurological damage.
*Gluten*
- **Gluten restriction** is primarily indicated for **celiac disease**, which presents with gastrointestinal symptoms like diarrhea, malabsorption, and poor weight gain, but not directly with hyperammonemia or urea cycle dysfunction.
- While malabsorption can cause poor weight gain, the specific metabolic derangements here point away from celiac disease.
*Lactose*
- **Lactose intolerance** or **galactosemia** would necessitate **lactose restriction**. Symptoms usually include vomiting, diarrhea, and failure to thrive, but they do not typically present with the extreme hyperammonemia seen here.
- Galactosemia specifically would show elevated galactose and galactose-1-phosphate, not ammonia.
*Fructose*
- **Hereditary fructose intolerance** requires **fructose restriction**. It generally presents with vomiting, hypoglycemia, and liver dysfunction (jaundice, hepatomegaly) upon exposure to fructose, not primarily with hyperammonemia.
- The metabolic pathway for fructose metabolism does not directly generate ammonia in the quantities seen with urea cycle disorders.
*Vitamin A*
- **Vitamin A restriction** is not a primary treatment for any known inborn error of metabolism or hyperammonemia.
- While deficiencies or toxicities of vitamins can occur, they do not present with the specific metabolic profile described (high ammonia, low citrulline).
Integration with TCA cycle US Medical PG Question 4: A startup is working on a novel project in which they claim they can replicate the organelle that is defective in MELAS syndrome. Which of the following metabolic processes must they be able to replicate if their project is to mimic the metabolic processes of this organelle?
- A. Hexose monophosphate shunt
- B. Cholesterol synthesis
- C. Glycolysis
- D. Fatty acid (beta) oxidation (Correct Answer)
- E. Fatty acid synthesis
Integration with TCA cycle Explanation: ***Fatty acid (beta) oxidation***
- **MELAS syndrome** (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is caused by defects in **mitochondrial function**.
- **Beta-oxidation of fatty acids** is a crucial metabolic process that occurs within the mitochondria, generating ATP.
*Hexose monophosphate shunt*
- The **hexose monophosphate shunt** (pentose phosphate pathway) occurs in the **cytosol** and is primarily involved in producing NADPH and synthesizing nucleotides, not a primary mitochondrial function.
- Its dysfunction is not directly linked to the core metabolic defects seen in MELAS syndrome.
*Cholesterol synthesis*
- **Cholesterol synthesis** primarily occurs in the **cytosol** and the **endoplasmic reticulum**, not within the mitochondria.
- While cholesterol metabolism can be indirectly affected by mitochondrial health, it is not a direct mitochondrial metabolic pathway.
*Glycolysis*
- **Glycolysis** is the metabolic pathway that converts glucose into pyruvate, occurring in the **cytosol**.
- Although it precedes mitochondrial oxidative phosphorylation, glycolysis itself does not occur within the mitochondria.
*Fatty acid synthesis*
- **Fatty acid synthesis** primarily takes place in the **cytosol** and endoplasmic reticulum, utilizing NADPH from the hexose monophosphate shunt.
- It is an anabolic process, while MELAS typically involves defects in catabolic/energy-producing mitochondrial pathways.
Integration with TCA cycle US Medical PG Question 5: A newborn boy develops projectile vomiting 48 hours after delivery. He is found to be lethargic, with poor muscle tone, and is hyperventilating. Within hours, he suffers important neurological deterioration, leading to seizures, coma, and, ultimately, death. An autopsy is performed and the pathology team makes a diagnosis of a rare genetic disorder that leads to low levels of N-acetylglutamate. Which of the following enzymes would be secondarily affected by this process?
- A. Argininosuccinate lyase
- B. Carbamoyl phosphate synthetase I (Correct Answer)
- C. Argininosuccinate synthetase
- D. Ornithine transcarbamylase
- E. Arginase
Integration with TCA cycle Explanation: ***Carbamoyl phosphate synthetase I***
- **N-acetylglutamate** is an **obligate activator** for **Carbamoyl phosphate synthetase I (CPS I)**, the rate-limiting enzyme of the **urea cycle**. Low levels of N-acetylglutamate directly impair CPS I activity.
- Reduced CPS I activity leads to a severe **urea cycle disorder**, causing **hyperammonemia**, which manifests with lethargy, poor muscle tone, hyperventilation, neurological deterioration, seizures, coma, and death in newborns.
*Argininosuccinate lyase*
- This enzyme is involved downstream in the **urea cycle**, catalyzing the cleavage of **argininosuccinate** into **arginine** and **fumarate**.
- Its activity is not directly regulated by **N-acetylglutamate**, so it would not be secondarily affected in the same manner as CPS I.
*Argininosuccinate synthetase*
- This enzyme acts after CPS I and ornithine transcarbamylase in the **urea cycle**, synthesizing **argininosuccinate** from **citrulline** and **aspartate**.
- Its function is independent of **N-acetylglutamate** levels, making it unlikely to be secondarily affected.
*Ornithine transcarbamylase*
- This enzyme catalyzes the second step of the **urea cycle**, forming **citrulline** from **ornithine** and **carbamoyl phosphate**.
- While essential for the urea cycle, its activity is not directly modulated by **N-acetylglutamate**; rather, it depends on the availability of carbamoyl phosphate produced by CPS I.
*Arginase*
- This is the final enzyme in the **urea cycle**, converting **arginine** to **ornithine** and **urea**.
- Its activity is not directly or indirectly regulated by **N-acetylglutamate**, nor is it the enzyme primarily affected in this presentation.
Integration with TCA cycle US Medical PG Question 6: A 24-year-old man is running a marathon. Upon reaching the finish line, his serum lactate levels were measured and were significantly increased as compared to his baseline. Which of the following pathways converts the lactate produced by muscles into glucose and transports it back to the muscles?
- A. Citric acid cycle
- B. Glycolysis
- C. Glycogenesis
- D. Pentose phosphate pathway
- E. Cori cycle (Correct Answer)
Integration with TCA cycle Explanation: ***Cori cycle***
- The **Cori cycle** is the metabolic pathway that converts **lactate** produced by anaerobic glycolysis in muscles (especially during intense exercise) back to **glucose in the liver** via gluconeogenesis.
- During strenuous exercise, muscles rely on anaerobic glycolysis when oxygen supply is insufficient, producing lactate and 2 ATP per glucose.
- The lactate is transported via bloodstream to the liver, where it is converted back to glucose (requiring 6 ATP), which then returns to muscles for energy or glycogen storage.
- This cycle allows muscles to continue generating ATP anaerobically while the liver handles lactate clearance.
*Citric acid cycle*
- The **citric acid cycle** (Krebs cycle) oxidizes **acetyl-CoA** to generate ATP, NADH, and FADH₂ in the mitochondrial matrix under aerobic conditions.
- It does not convert lactate to glucose; rather, pyruvate can be converted to acetyl-CoA to enter this cycle for complete oxidation.
- This is an aerobic process and does not involve the liver-muscle lactate-glucose exchange.
*Glycolysis*
- **Glycolysis** is the metabolic pathway that breaks down **glucose into pyruvate**, generating 2 ATP and 2 NADH per glucose molecule.
- Under anaerobic conditions, pyruvate is converted to lactate to regenerate NAD⁺ for continued glycolysis.
- This is the opposite of what the question asks—glycolysis produces lactate from glucose, not glucose from lactate.
*Glycogenesis*
- **Glycogenesis** is the process of synthesizing **glycogen from glucose** for storage, primarily in liver and muscle tissue.
- While it involves glucose storage, it does not convert lactate back to glucose or involve the metabolic exchange between muscles and liver described in the question.
*Pentose phosphate pathway*
- The **pentose phosphate pathway** (hexose monophosphate shunt) produces **NADPH** for reductive biosynthesis and **ribose-5-phosphate** for nucleotide synthesis.
- It branches from glycolysis but is not involved in lactate metabolism or the muscle-liver glucose-lactate exchange.
Integration with TCA cycle US Medical PG Question 7: During normal respiration in the lungs, oxygen is absorbed into the bloodstream and carbon dioxide is released. The oxygen is used in cells as the final electron acceptor during oxidative phosphorylation, and carbon dioxide is generated during each turn of the tricarboxylic citric acid cycle (TCA). Which of the following steps in the TCA cycle represents the first decarboxylation reaction that generates carbon dioxide?
- A. Isocitrate to alpha ketoglutarate (Correct Answer)
- B. Fumarate to Malate
- C. Citrate to isocitrate
- D. Malate to oxaloacetate
- E. Alpha-ketoglutarate to Succinyl-CoA
Integration with TCA cycle Explanation: ***Isocitrate to alpha ketoglutarate***
- This is the **first decarboxylation reaction** in the TCA cycle, catalyzed by **isocitrate dehydrogenase**.
- During this reaction, **isocitrate** is oxidized and a molecule of **carbon dioxide** is released, along with the reduction of NAD+ to NADH.
- This is one of the three irreversible steps in the TCA cycle and a key regulatory point.
*Fumarate to Malate*
- This step involves the **hydration** of **fumarate** to **malate** by the enzyme **fumarase**.
- There is no release of carbon dioxide in this reaction; it's a simple addition of water.
*Citrate to isocitrate*
- This is an **isomerization** reaction, catalyzed by **aconitase**, where **citrate** is rearranged into its isomer, **isocitrate**.
- This step does not involve the removal of carbon atoms or the production of carbon dioxide.
*Malate to oxaloacetate*
- In this step, **malate** is oxidized to **oxaloacetate** by **malate dehydrogenase**, which produces NADH.
- This is an **oxidation** reaction, not a decarboxylation reaction, and no carbon dioxide is released.
*Alpha-ketoglutarate to Succinyl-CoA*
- This is the **second decarboxylation** step in the TCA cycle, catalyzed by the **alpha-ketoglutarate dehydrogenase complex**.
- While this step also produces carbon dioxide and reduces NAD+ to NADH, it occurs after the isocitrate to alpha-ketoglutarate step, making it the second rather than the first decarboxylation reaction.
Integration with TCA cycle US Medical PG Question 8: A 4-day-old boy is brought to the physician because of somnolence, poor feeding, and vomiting after his first few breast feedings. He appears lethargic. His respiratory rate is 73/min. Serum ammonia is markedly increased. Genetic analysis shows deficiency in N-acetylglutamate synthase. The activity of which of the following enzymes is most likely directly affected by this genetic defect?
- A. Ornithine translocase
- B. Carbamoyl phosphate synthetase I (Correct Answer)
- C. Argininosuccinase
- D. Argininosuccinate synthetase
- E. Arginase
Integration with TCA cycle Explanation: ***Carbamoyl phosphate synthetase I***
- **N-acetylglutamate** (NAG) is an essential allosteric activator of **carbamoyl phosphate synthetase I (CPS I)**, the rate-limiting enzyme of the urea cycle.
- A deficiency in **N-acetylglutamate synthase** directly leads to a lack of NAG, significantly impairing CPS I activity and causing severe hyperammonemia.
*Ornithine translocase*
- This enzyme is responsible for transporting **ornithine** into the mitochondria for the urea cycle.
- While a defect in **ornithine translocase** also causes hyperammonemia, it is due to accumulation of ornithine and upstream substrates, not a defect in N-acetylglutamate synthase.
*Argininosuccinase*
- Also known as **argininosuccinate lyase**, this enzyme cleaves argininosuccinate into arginine and fumarate.
- A deficiency would lead to accumulation of **argininosuccinate**, and while it is a urea cycle disorder, it is not directly affected by N-acetylglutamate synthase deficiency.
*Argininosuccinate synthetase*
- This enzyme catalyzes the condensation of **citrulline** and **aspartate** to form argininosuccinate.
- A defect in **argininosuccinate synthetase** causes citrullinemia but is not directly regulated by N-acetylglutamate.
*Arginase*
- **Arginase** is the final enzyme in the urea cycle, hydrolyzing arginine to form urea and ornithine.
- A deficiency would lead to hyperargininemia, which typically presents later in childhood and is not directly affected by N-acetylglutamate.
Integration with TCA cycle US Medical PG Question 9: A 12-year-old boy and his siblings are referred to a geneticist for evaluation of a mild but chronic hemolytic anemia that has presented with fatigue, splenomegaly, and scleral icterus. Coombs test is negative and blood smear does not show any abnormal findings. An enzymatic panel is assayed, and pyruvate kinase is found to be mutated on both alleles. The geneticist explains that pyruvate kinase functions in glycolysis and is involved in a classic example of feed-forward regulation. Which of the following metabolites is able to activate pyruvate kinase?
- A. Fructose-1,6-bisphosphate (Correct Answer)
- B. Alanine
- C. ATP
- D. Glucose-6-phosphate
- E. Glyceraldehyde-3-phosphate
Integration with TCA cycle Explanation: ***Fructose-1,6-bisphosphate***
- **Fructose-1,6-bisphosphate** is a potent **allosteric activator** of pyruvate kinase. This is an example of **feed-forward activation**, where a product of an early irreversible step in glycolysis (catalyzed by phosphofructokinase-1) activates a later enzyme (pyruvate kinase) in the pathway.
- This activation ensures that substrates for the later steps of glycolysis are rapidly utilized when earlier steps are highly active, matching the rate of metabolite flow and increasing the overall efficiency of glycolysis for energy production.
*Alanine*
- **Alanine** is an **inhibitor** of pyruvate kinase, not an activator. It serves as an indicator of a high cellular energy state and ample amino acid supply.
- High levels of alanine signal the cell that there is sufficient energy and building blocks, thus **shutting down** glycolysis at the pyruvate kinase step to conserve glucose for other needs like glycogen synthesis.
*ATP*
- **ATP** (adenosine triphosphate) is an **allosteric inhibitor** of pyruvate kinase. High ATP levels signal a high energy state in the cell.
- When the cell has sufficient energy, ATP binds to a regulatory site on pyruvate kinase, reducing its activity and **slowing down glycolysis** to prevent overproduction of ATP.
*Glucose-6-phosphate*
- **Glucose-6-phosphate** is an intermediate in glycolysis but does not directly activate pyruvate kinase. It can act as an allosteric inhibitor of hexokinase, the first enzyme in glycolysis, but not pyruvate kinase.
- Its accumulation typically signifies a **backup** in the glycolytic pathway (e.g., due to downstream inhibition), leading to a *reduction* in overall glucose flux rather than a direct activation of pyruvate kinase.
*Glyceraldehyde-3-phosphate*
- **Glyceraldehyde-3-phosphate** is an intermediate in glycolysis, but it does not directly activate pyruvate kinase. It is a substrate for glyceraldehyde-3-phosphate dehydrogenase.
- While its presence indicates active glycolysis, it does not exert a specific allosteric regulatory effect on pyruvate kinase in the way fructose-1,6-bisphosphate does.
Integration with TCA cycle US Medical PG Question 10: A 4-year-old boy presents with vomiting and one day of lethargy after a one week history of flu-like symptoms and low-grade fevers. The vomiting is nonbilious and nonbloody. The patient has had no other symptoms aside from mild rhinorrhea and cough. He has no past medical history, and is on no medications except for over-the-counter medications for his fever. His temperature is 98.5°F (36.9°C), pulse is 96/min, respirations are 14/min, and blood pressure is 108/80 mmHg. The patient appears lethargic and is oriented only to person. Otherwise, the physical exam is benign and the patient has no other neurologic symptoms. What is the mechanism of the most likely cause of this patient’s presentation?
- A. Deficient erythrocyte enzyme
- B. Chemical ingestion
- C. Bacterial infection
- D. Irreversible enzyme inhibition (Correct Answer)
- E. Reversible enzyme inhibition
Integration with TCA cycle Explanation: ***Irreversible enzyme inhibition***
- This presentation is highly suggestive of **Reye syndrome**, which is associated with **aspirin use** in children with viral illnesses. Aspirin (acetylsalicylic acid) **irreversibly inhibits cyclooxygenase (COX) enzymes** by acetylating a serine residue at the active site.
- While aspirin's primary mechanism is COX inhibition, **Reye syndrome** involves **mitochondrial dysfunction** in hepatocytes, leading to impaired fatty acid beta-oxidation, hyperammonemia, hepatic steatosis, and **encephalopathy**. This explains the vomiting, lethargy, and altered mental status after flu-like symptoms.
- The key connection is that aspirin acts through **irreversible enzyme inhibition**, making this the correct mechanistic classification for the causative agent.
*Reversible enzyme inhibition*
- While some aspects of Reye syndrome involve mitochondrial enzyme dysfunction, aspirin itself does **not** act through reversible competitive inhibition—it **irreversibly acetylates** COX enzymes.
- Reversible inhibition would imply the drug effect could be easily overcome by increasing substrate concentration, which is not the case with aspirin's mechanism.
*Deficient erythrocyte enzyme*
- This mechanism is associated with conditions like **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, which primarily causes **hemolytic anemia** with jaundice and pallor.
- While G6PD deficiency can be triggered by certain medications, it does not typically present with the **encephalopathy** and liver dysfunction seen in this patient.
*Chemical ingestion*
- While aspirin is technically a chemical, the question asks about the **mechanism** rather than the route of exposure. The specific mechanism is irreversible enzyme inhibition.
- The history of **flu-like symptoms** and use of over-the-counter fever medications strongly suggests aspirin-associated Reye syndrome rather than accidental toxic ingestion.
*Bacterial infection*
- A severe bacterial infection (e.g., **bacterial meningitis** or **sepsis**) could cause lethargy and vomiting, but the clinical picture (normal vital signs, benign physical exam, no fever) is not typical for acute bacterial infection.
- The association with a recent **viral illness** and potential over-the-counter medication use strongly favors Reye syndrome, a non-infectious etiology.
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