Urea cycle

Urea cycle US Medical PG Question 1: A 2-day-old male infant is brought to the emergency department by ambulance after his parents noticed that he was convulsing and unresponsive. He was born at home and appeared well initially; however, within 24 hours he became increasingly irritable and lethargic. Furthermore, he stopped feeding and began to experience worsening tachypnea. This continued for about 6 hours, at which point his parents noticed the convulsions and called for an ambulance. Laboratories are obtained with the following results: Orotic acid: 9.2 mmol/mol creatinine (normal: 1.4-5.3 mmol/mol creatinine) Ammonia: 135 µmol/L (normal: < 50 µmol/L) Citrulline: 2 µmol/L (normal: 10-45 µmol/L) Which of the following treatments would most likely be beneficial to this patient?

• A. Galactose avoidance
• B. Aspartame avoidance
• C. Benzoate administration (Correct Answer)
• D. Uridine administration
• E. Fructose avoidance

Urea cycle Explanation: ***Benzoate administration*** - This patient presents with hyperammonemia (135 µmol/L), elevated orotic acid (9.2 mmol/mol creatinine), and **low citrulline (2 µmol/L)**, which is the classic triad for **ornithine transcarbamylase (OTC) deficiency**. - The low citrulline distinguishes OTC deficiency from other urea cycle defects, while elevated orotic acid results from accumulation of carbamoyl phosphate that gets shunted into pyrimidine synthesis. - **Sodium benzoate** is a nitrogen scavenger that conjugates with glycine to form hippurate, which is excreted renally, providing an alternative pathway for nitrogen disposal and reducing toxic ammonia levels. - This is a life-saving acute treatment for hyperammonemia in urea cycle disorders. *Galactose avoidance* - This is the treatment for **galactosemia**, a disorder of galactose metabolism caused by galactose-1-phosphate uridyltransferase deficiency. - Galactosemia presents with hepatomegaly, jaundice, cataracts, intellectual disability, and hypoglycemia after milk feeding. - The patient's hyperammonemia and elevated orotic acid pattern is incompatible with galactosemia. *Aspartame avoidance* - This is relevant for **phenylketonuria (PKU)** dietary management, as aspartame contains phenylalanine. - PKU presents with developmental delay, intellectual disability, musty odor, and eczema, with elevated phenylalanine levels. - Ammonia and orotic acid are normal in PKU, making this diagnosis inconsistent with the lab findings. *Uridine administration* - **Uridine** treats **hereditary orotic aciduria** (UMP synthase deficiency), which presents with megaloblastic anemia, growth retardation, and developmental delays. - While orotic acid is elevated in both conditions, hereditary orotic aciduria has **normal ammonia** and the primary pathology is impaired pyrimidine synthesis, not ammonia disposal. - This patient's life-threatening hyperammonemia requires immediate nitrogen scavenging, which uridine does not provide. *Fructose avoidance* - This treats **hereditary fructose intolerance** (aldolase B deficiency), which causes hypoglycemia, vomiting, hepatomegaly, and jaundice after fructose ingestion. - The presentation is triggered by dietary fructose exposure and does not cause hyperammonemia or elevated orotic acid. - The patient's metabolic profile is inconsistent with a fructose metabolism disorder.

Urea cycle US Medical PG Question 2: A 36-year-old man is brought to the emergency department by his girlfriend because of increasing confusion for the past 6 hours. He drinks large amounts of alcohol daily and occasionally uses illicit drugs. He is lethargic and oriented only to person. Physical examination shows jaundice, hepatomegaly, and scattered petechiae over the trunk and back. Neurologic examination shows normal, reactive pupils and a flapping tremor when the wrists are extended. A drug with which of the following mechanism of action would be most appropriate for this patient's condition?

• A. Production of NH3
• B. Activation of GABA receptors
• C. Excretion of free iron
• D. Inhibition of D2 receptors
• E. Excretion of NH4 (Correct Answer)

Urea cycle Explanation: ***Excretion of NH4*** - The patient presents with **hepatic encephalopathy**, characterized by **confusion**, **jaundice**, **hepatomegaly**, **petechiae**, and a **flapping tremor (asterixis)**, stemming from chronic alcohol abuse and liver damage. The main pathophysiology in hepatic encephalopathy is the accumulation of **ammonia (NH3)**, which is neurotoxic. - Excretion of **NH4** (ammonium) through drug mechanisms such as **lactulose** (which acidifies the colon, trapping ammonia as ammonium for excretion) is the primary therapeutic target to reduce ammonia levels and improve neurological symptoms. *Production of NH3* - This mechanism would exacerbate the patient's condition by increasing the toxic load of **ammonia (NH3)**, which is already elevated in hepatic encephalopathy. - Therapeutic interventions aim to decrease, not increase, ammonia production or absorption. *Activation of GABA receptors* - While **GABA receptor activation** is involved in the neurological effects of some substances that contribute to confusion, it is not the primary target for treating the underlying pathophysiology of **hepatic encephalopathy**. - Medications that activate GABA receptors (e.g., benzodiazepines) can worsen encephalopathy by further depressing CNS function. *Excretion of free iron* - **Iron overload** can cause liver damage, but the acute confusion and flapping tremor are more indicative of **hepatic encephalopathy** due to ammonia toxicity, not primarily iron accumulation. - Excreting free iron (e.g., with chelation therapy) is for conditions like hemochromatosis and would not address the immediate, life-threatening neurological symptoms in this patient. *Inhibition of D2 receptors* - This mechanism is characteristic of some **antipsychotic medications**. While dopamine imbalances can play a role in some neurological disorders, inhibiting D2 receptors is not a primary therapeutic target for **hepatic encephalopathy**. - Such medications could have side effects that might complicate the clinical picture in a patient with acute liver failure.

Urea cycle US Medical PG Question 3: 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

Urea 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.

Urea cycle US Medical PG Question 4: 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)

Urea 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.

Urea cycle US Medical PG Question 5: A 65-year old man comes to the emergency department because of altered mental status for 1 day. He has had headaches, severe nausea, vomiting, and diarrhea for 2 days. He has a history of hypertension, insomnia, and bipolar disorder. His medications include lisinopril, fluoxetine, atorvastatin, lithium, olanzapine, and alprazolam. His temperature is 37.2 °C (99.0 °F), pulse is 90/min, respirations are 22/min, and blood pressure is 102/68 mm Hg. He is somnolent and confused. His mucous membranes are dry. Neurological examination shows dysarthria, decreased muscle strength throughout, and a coarse tremor of the hands bilaterally. The remainder of the examination shows no abnormalities. In addition to IV hydration and electrolyte supplementation, which of the following is the next best step in management?

• A. Bowel irrigation
• B. Intravenous diazepam
• C. Oral cyproheptadine
• D. Intravenous dantrolene
• E. Hemodialysis (Correct Answer)

Urea cycle Explanation: ***Hemodialysis*** - This patient presents with symptoms consistent with **severe lithium toxicity** (altered mental status, somnolence, confusion, dysarthria, decreased muscle strength, coarse tremor) likely exacerbated by dehydration due to nausea, vomiting, and diarrhea. - **Hemodialysis** is indicated for severe lithium toxicity, especially when plasma lithium levels are very high (>4.0 mEq/L), there are signs of cerebellar toxicity or seizures, or if renal impairment prevents adequate lithium excretion. *Bowel irrigation* - **Whole-bowel irrigation** is primarily used for large ingestions of sustained-release or enteric-coated medications, or substances not adsorbed by activated charcoal. - It is generally *not* effective for removing lithium, as lithium is rapidly and completely absorbed from the gastrointestinal tract. *Intravenous diazepam* - **Benzodiazepines** like diazepam are useful for managing seizures or severe agitation associated with drug toxicities but do not address the underlying cause of lithium toxicity by removing the drug from the body. - While agitation and seizures might occur in severe lithium toxicity, the primary initial step in severe cases is to remove the excess lithium. *Oral cyproheptadine* - **Cyproheptadine** is an antihistamine with antiserotonergic properties, used in the treatment of **serotonin syndrome**. - This patient's clinical presentation is classic for **lithium toxicity**, not serotonin syndrome, although fluoxetine can contribute to serotonin syndrome, the tremor and neurological picture coupled with lithium use points to lithium toxicity. *Intravenous dantrolene* - **Dantrolene** is a muscle relaxant primarily used for conditions like **neuroleptic malignant syndrome** (NMS) or malignant hyperthermia due to its direct action on skeletal muscle. - It is not indicated for treating the central nervous system effects or removal of lithium in lithium toxicity.

Urea cycle US Medical PG Question 6: 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

Urea cycle 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.

Urea cycle US Medical PG Question 7: 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

Urea 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.

Urea cycle US Medical PG Question 8: A 2-week-old boy presents to the emergency department because of unusual irritability and lethargy. The patient is admitted to the pediatric intensive care unit and minutes later develops metabolic encephalopathy. This progressed to a coma, followed by death before any laboratory tests are completed. The infant was born at home via vaginal delivery at 39 weeks' of gestation. His mother says that the symptoms started since the infant was 4-days-old, but since he only seemed ‘tired’, she decided not to seek medical attention. Further testing during autopsy shows hyperammonemia, low citrulline, and increased orotic acid. Which of the following enzymes is most likely deficient in this patient?

• A. Branched-chain alpha-ketoacid dehydrogenase
• B. Propionyl-CoA carboxylase
• C. Homogentisic acid dioxygenase
• D. Ornithine transcarbamylase (Correct Answer)
• E. Cystathionine beta-synthase

Urea cycle Explanation: **Ornithine transcarbamylase** - **Hyperammonemia**, **low citrulline**, and **increased orotic acid** are classic findings in **Ornithine Transcarbamylase (OTC) deficiency**. OTC is an X-linked urea cycle disorder. - The rapid progression to **metabolic encephalopathy** and death in a neonate with these laboratory findings is highly characteristic of severe OTC deficiency, often presenting in the first few days of life. *Branched-chain alpha-ketoacid dehydrogenase* - Deficiency of this enzyme causes **Maple Syrup Urine Disease**, characterized by elevated **branched-chain amino acids** and their corresponding ketoacids in blood and urine. - While it can cause neurological symptoms, it does not typically present with the specific constellation of **hyperammonemia**, low citrulline, and high orotic acid. *Propionyl-CoA carboxylase* - Deficiency of this enzyme leads to **Propionic acidemia**, a type of organic acidemia, characterized by **propionic acid accumulation** and often **metabolic acidosis**, ketosis, and hyperammonemia. - However, it would not typically cause **low citrulline** or isolated **elevated orotic acid** as seen in urea cycle disorders. *Homogentisic acid dioxygenase* - Deficiency of this enzyme causes **Alkaptonuria**, an inborn error of metabolism characterized by the accumulation of **homogentisic acid**. - This condition is usually benign in infancy, with symptoms appearing later in life such as **dark urine** on standing and **ochronosis** (darkening of cartilage). It does not present with acute hyperammonemia or metabolic encephalopathy. *Cystathionine beta-synthase* - Deficiency of this enzyme causes **homocystinuria**, an inborn error of methionine metabolism, leading to elevated **homocysteine** and methionine. - Clinical features include **ectopia lentis**, skeletal abnormalities, and intellectual disability, but not usually acute neonatal hyperammonemia or the specific findings of low citrulline and high orotic acid.

Urea cycle US Medical PG Question 9: 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

Urea 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).

Urea cycle US Medical PG Question 10: A 4-year-old girl is brought to the physician by her mother because of fatigue and generalized weakness for 4 months. Examination shows decreased muscle tone. Her fasting serum glucose concentration is 41 mg/dL. The physician suspects a defect in one of the enzymes involved in the carnitine shuttle. Increased serum concentration of which of the following should most raise suspicion of a different diagnosis?

• A. Ammonia (Correct Answer)
• B. Creatine kinase
• C. Alanine aminotransferase
• D. Uric acid
• E. β-hydroxybutyrate

Urea cycle Explanation: ***Ammonia*** - An elevated **ammonia** level in the context of hypoglycemia and muscle weakness in a child suggests an **inborn error of metabolism** that affects the **urea cycle** or **organic acidemia**, not primarily the carnitine shuttle. - Urea cycle disorders lead to **hyperammonemia**, which can cause neurological symptoms, fatigue, and muscle weakness, often exacerbated by catabolic states. - This finding would **strongly suggest a different diagnosis** from a carnitine shuttle defect. *Creatine kinase* - **Creatine kinase (CK)** levels are typically **elevated in carnitine shuttle defects** due to muscle damage and myopathy. - Elevated CK would **support** the suspected diagnosis of a carnitine shuttle defect rather than suggest an alternative. - This is an **expected finding** in fatty acid oxidation disorders. *Alanine aminotransferase* - **Alanine aminotransferase (ALT)** can be elevated in **carnitine shuttle defects** due to liver involvement and hepatic dysfunction. - While elevated ALT indicates liver damage, it can occur in fatty acid oxidation disorders and would not necessarily point away from a carnitine shuttle defect. - This finding is **consistent with** rather than against the suspected diagnosis. *Uric acid* - **Uric acid** levels are not directly affected by defects in the **carnitine shuttle**. - While an elevated uric acid level might prompt investigation into conditions like **glycogen storage diseases** or purine metabolism disorders, it is not a strong discriminator for alternative diagnoses in this clinical context. *β-hydroxybutyrate* - **β-hydroxybutyrate** is a **ketone body** produced from fatty acid oxidation during fasting states. - In carnitine shuttle defects, the body **cannot effectively oxidize fatty acids** to produce ketones, resulting in **hypoketotic hypoglycemia** (low or inappropriately low ketones despite low glucose). - If β-hydroxybutyrate is **elevated** during fasting hypoglycemia, this indicates **intact fatty acid oxidation** and would suggest a different diagnosis such as **hyperinsulinism**, **glycogen storage disease**, or other causes of hypoglycemia where ketogenesis is preserved. - However, **ammonia elevation** is a stronger indicator of an alternative diagnosis (urea cycle disorder) compared to the scenario presented.

Urea cycle Flashcard 1 of 10

Question: In the liver, _____ may transfer a molecule of NH3 to the urea cycle, reforming -ketoglutarate

Answer: glutamate

Urea cycle Flashcard 2 of 10

Question: Ornithine transcarbamylase (OTC) deficiency presents with increased _____ acid in the blood and urine

Answer: orotic

Urea cycle Flashcard 3 of 10

Question: Where does the urea cycle occur?

Answer: steps in both the cytoplasm and mitochondria

Urea cycle Flashcard 4 of 10

Question: urea cycle

Answer: carbomoyl phosphate synthetase I

Urea cycle Flashcard 5 of 10

Question: What is the overall purpose of the urea cycle?

Answer: to get NH4+ from amino acid catabolism into an excretable form

Urea cycle Flashcard 6 of 10

Question: carbomoyl phosphate synthetase I

Answer: urea cycle

Extra Information: N-acetylglutamate

Urea cycle Flashcard 7 of 10

Question: In which pathway is ornithine transcarbamylase involved?

Answer: urea cycle

Urea cycle Flashcard 8 of 10

Question: In which pathways is carbamoyl phosphate involved?

Answer: de novo pyrimidine synthesis; urea cycle

Urea cycle Flashcard 9 of 10

Question: ornithine transcarbamylase (OTC) deficiency

Answer:

Extra Information: inability to eliminate ammoniasomnolence in infantincreased orotic acid in blood and urine, hyperammonemia (and symptoms thereof)same as tx for any hepatic encephalopathy i.e. restrict protein in diet, benzoate or phenylbutyrate, lactulose XR ornithine transcarbamoylase

Urea cycle Flashcard 10 of 10

Question: How do levels of serum BUN change with liver dysfunction? _____

Answer: Decreased

Extra Information:   https://onlinemeded.org/spa/metabolism/urea-cycle/acquire?ref=anki