Amino Acid Metabolism Practice Questions

Q: Abnormal mousy/mushy odour of urine is associated with which condition?

Phenylketonuria. **Explanation:** The correct answer is **Phenylketonuria (PKU)**. PKU is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme **phenylalanine hydroxylase**, which converts phenylalanine to tyrosine. This leads to the accumulation of phenylalanine and its metabolites, such as **phenylacetic acid**, in the urine. The characteristic **mousy or musty odor** is specifically attributed to phenylacetic acid. **Analysis of Options:** * **Phenylketonuria (Correct):** Associated with a mousy/musty odor, intellectual disability, seizures, and hypopigmentation (fair skin/blue eyes) due to decreased melanin synthesis. * **Tyrosinemia:** Characterized by a **boiled cabbage-like** or **rancid butter** odor. It often presents with liver failure, renal tubular dysfunction (Fanconi syndrome), and rickets. * **Maple Syrup Urine Disease (MSUD):** Caused by a deficiency in the branched-chain alpha-keto acid dehydrogenase complex. It results in a distinct **burnt sugar or maple syrup** odor of the urine. * **Hawkinsuria:** A rare defect in tyrosine metabolism (4-hydroxyphenylpyruvate dioxygenase deficiency) that typically presents with a **swimming pool or chlorine-like** odor. **Clinical Pearls for NEET-PG:** * **Isovaleric Acidemia:** Sweaty feet odor. * **Trimethylaminuria:** Fishy odor. * **Multiple Carboxylase Deficiency:** Tomcat urine odor. * **Oasthouse Urine Disease (Methionine Malabsorption):** Dried malt or hops odor. * **Screening:** The **Guthrie Test** (bacterial inhibition assay) is the classic screening method for PKU, though Tandem Mass Spectrometry (TMS) is now the gold standard.

Q: Inherited hyperammonemia is a result of deficiency of which enzyme of the Krebs-Henseleit urea cycle?

N-acetyl glutamate synthetase. ### Explanation **Correct Option: C. N-acetyl glutamate synthetase (NAGS)** The **Krebs-Henseleit cycle (Urea Cycle)** is the primary mechanism for detoxifying ammonia into urea. The first and rate-limiting enzyme of this cycle is **Carbamoyl Phosphate Synthetase I (CPS-I)**. However, CPS-I is inactive without its essential allosteric activator, **N-acetylglutamate (NAG)**. NAG is synthesized from acetyl-CoA and glutamate by the enzyme **N-acetylglutamate synthetase (NAGS)**. A deficiency in NAGS leads to a failure to activate CPS-I, resulting in a complete block of the urea cycle. This causes a toxic buildup of ammonia in the blood (**Hyperammonemia**), leading to encephalopathy and cerebral edema. **Analysis of Incorrect Options:** * **A, B, and D (Malate, Isocitrate, and Succinate Dehydrogenase):** These are enzymes of the **TCA Cycle (Krebs Cycle)**, not the Urea Cycle. While the TCA cycle provides the ATP and aspartate required for the urea cycle, deficiencies in these specific enzymes do not typically present with isolated primary hyperammonemia. **Clinical Pearls for NEET-PG:** * **Most Common Urea Cycle Disorder:** Ornithine Transcarbamoylase (OTC) deficiency (X-linked recessive). * **NAGS Deficiency Mimicry:** NAGS deficiency clinically mimics CPS-I deficiency. Both present with hyperammonemia and **low/absent orotic acid** levels. * **Treatment:** NAGS deficiency is unique because it can be treated with **Carglumic acid** (an analog of N-acetylglutamate), which directly activates CPS-I. * **Mnemonic:** "NAGS is the key that unlocks CPS-I."

Q: A 2-month-old infant presents with poor feeding, vomiting, and lethargy. Laboratory studies show hyperammonemia and elevated levels of orotic acid in the urine. Which of the following is the most likely enzyme deficiency?

Ornithine transcarbamylase (OTC) deficiency. ***Ornithine transcarbamylase (OTC) deficiency*** - **Most common X-linked urea cycle disorder** presenting in infancy with hyperammonemia - **Classic triad:** Hyperammonemia + elevated urinary orotic acid + low blood urea nitrogen - **Biochemical mechanism:** OTC converts carbamoyl phosphate + ornithine → citrulline. When deficient, carbamoyl phosphate accumulates and spills into the pyrimidine synthesis pathway, producing excess orotic acid - Clinical features: poor feeding, vomiting, lethargy, seizures, developmental delay *Carbamoyl phosphate synthetase I (CPS I) deficiency* - Also causes hyperammonemia but **NO orotic aciduria** (defect occurs before OTC step) - Carbamoyl phosphate is not formed, so cannot enter pyrimidine pathway - Cannot be distinguished clinically from OTC deficiency without measuring orotic acid *Argininosuccinate lyase deficiency* - Causes hyperammonemia with elevated **argininosuccinate** in blood/urine - Does not cause orotic aciduria (defect is downstream of OTC) - May present with trichorrhexis nodosa (brittle hair) *Orotidine 5′-phosphate decarboxylase deficiency* - Causes hereditary **orotic aciduria** but **NO hyperammonemia** (not a urea cycle disorder) - Defect in de novo pyrimidine synthesis pathway - Presents with megaloblastic anemia, growth retardation, responds to uridine supplementation

Q: A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

Homogentisate oxidase. ***Homogentisate oxidase***- Deficiency of this enzyme causes **Alkaptonuria**, resulting in the accumulation of **homogentisic acid**, which oxidizes into dark polymeric pigment called **ochronotic pigment**.- This pigment deposits in cartilage and connective tissues (**Ochronosis**), leading to severe destructive arthritis, especially in large joints, and causing the characteristic **blackening of joint tissues** observed on arthroscopy.*Branched-chain alpha-ketoacid dehydrogenase*- Deficiency of this enzyme causes **Maple Syrup Urine Disease (MSUD)**, leading to the accumulation of **branched-chain amino acids** (leucine, isoleucine, valine).- MSUD is characterized by severe neurologic dysfunction and a distinctive maple syrup odor in the urine, not chronic arthritis or joint pigmentation.*Tyrosinase*- This enzyme is crucial for the synthesis of **melanin** from tyrosine.- Deficiency results in conditions like **Albinism**, characterized by hypopigmentation of the skin, hair, and eyes, which is distinct from ochronotic arthritis.*Fumarase*- Deficiency of this enzyme (Fumarate hydratase) impairs the **Krebs cycle** (TCA cycle).- Clinical features include severe intellectual disability, microcephaly, and metabolic acidosis, without the development of ochronosis or black joints.

Q: Nitric oxide is synthesized from which of the following amino acids?

Arginine. ***Arginine*** - **L-arginine** is the sole biological precursor for nitric oxide (NO), a crucial signaling molecule involved in vasodilation, neurotransmission, and immune response. - The synthesis is catalyzed by the family of enzymes known as **nitric oxide synthases (NOS)**, which convert L-arginine into NO and **L-citrulline**. *Tryptophan* - Tryptophan is an essential amino acid that serves primarily as the precursor for the synthesis of the neurotransmitter **serotonin** and the hormone **melatonin**. - It is metabolized via the **kynurenine pathway** and is not utilized in the reaction catalyzed by NOS. *Lysine* - Lysine is an essential amino acid important for protein synthesis, and it is a precursor for **carnitine**, which is vital for fatty acid metabolism. - It is a basic amino acid and is not the substrate required by nitric oxide synthase for NO generation. *Tyrosine* - Tyrosine is the precursor amino acid necessary for the synthesis of **catecholamines** (dopamine, norepinephrine, epinephrine) and the **thyroid hormones**. - Though part of various metabolic pathways, it is not involved in the direct enzymatic conversion that yields nitric oxide.

Q: A patient has elevated phenylalanine levels (40 mg/dL), but phenylalanine hydroxylase enzyme levels are normal. Which cofactor deficiency is most likely responsible for this condition?

Tetrahydrobiopterin (BH4). ***Tetrahydrobiopterin (BH4)*** - The conversion of **phenylalanine to tyrosine** by phenylalanine hydroxylase (PAH) absolutely requires the cofactor **Tetrahydrobiopterin (BH4)**. - Normal PAH enzyme levels combined with high phenylalanine (hyperphenylalaninemia) strongly indicates a defect in the essential cofactor (BH4 deficiency), often leading to a potentially treatable condition known as **Malignant PKU**. *Tetrahydrofolate* - **Tetrahydrofolate (THF)** is primarily involved in **one-carbon metabolism** and the transfer of methyl groups, crucial for purine and pyrimidine synthesis. - Its deficiency typically leads to **megaloblastic anemia** and neurological symptoms but does not directly impair phenylalanine hydroxylase activity. *Thiamine* - The active form, **Thiamine Pyrophosphate (TPP)**, is an essential cofactor for **dehydrogenase enzymes**, such as pyruvate dehydrogenase and $\alpha$-ketoglutarate dehydrogenase. - Deficiency is classically associated with impaired carbohydrate metabolism and results in conditions like **Beriberi**. *Pyridoxine* - **Pyridoxal phosphate (PLP)**, derived from pyridoxine, is a cofactor for manifold reactions in amino acid metabolism, including **transaminases** and decarboxylases. - While vital for general amino acid handling, it is not the required cofactor for the specific hydroxylation reaction catalyzed by **phenylalanine hydroxylase**.

Q: The image shows a biochemical pathway. Name the enzyme marked as X.

Creatine Kinase. ***Creatine Kinase*** - The image shows the synthesis of creatine, and the final step involves the conversion of **creatine** to **creatine phosphate** using **ATP**, which is typical of a kinase enzyme. - **Creatine kinase** (CK) catalyzes the reversible transfer of a phosphate group from ATP to creatine, forming phosphocreatine and ADP, or vice versa, playing a crucial role in energy storage in muscle. *Creatine Phosphorylase* - This term is not a standard or commonly recognized name for an enzyme in biochemistry. While it might sound related to phosphorylation of creatine, **creatine kinase (CK)** is the correct and widely accepted enzyme name. - Enzymes are named based on their function and substrate; "phosphorylase" usually refers to enzymes that cleave bonds using inorganic phosphate, which is not the reaction shown here. *Argininosuccinase* - **Argininosuccinase (argininosuccinate lyase)** is an enzyme involved in the **urea cycle**, catalyzing the cleavage of argininosuccinate into arginine and fumarate. - This enzyme is not involved in creatine metabolism and its reaction mechanism is distinct from the phosphorylation shown in the diagram. *Ornithine transcarbamoylase* - **Ornithine transcarbamoylase** (OTC) is another enzyme of the **urea cycle**, catalyzing the reaction between carbamoyl phosphate and ornithine to form citrulline. - Its function is entirely unrelated to the synthesis or phosphorylation of creatine and does not involve ATP-ADP interconversion in this manner.

Question 1

Which of the following clinical laboratory observations is suggestive of Maple syrup urine disease?

Accepted Answer

High fecal levels of tryptophan and indole derivatives

Answer

Burnt sugar smell in urine

Answer

High plasma phenylalanine levels

Answer

Extremely high levels of citrulline in urine

Question 2

Diagnosis of carcinoid tumors is done by?

Accepted Answer

5-HIAA

Answer

DHEA

Answer

DHEA

Answer

Metanephrines

Question 3

A 1-year-old child presents with delayed milestones. Examination reveals fair skin with hypopigmented hair and blue eyes. The child also has eczema and is irritable. What is the most likely diagnosis?

Accepted Answer

Phenylketonuria

Answer

Albinism

Answer

Alkaptonuria

Answer

Cystinosis

Question 4

Abnormal mousy/mushy odour of urine is associated with which condition?

Accepted Answer

Phenylketonuria

Answer

Tyrosinemia

Answer

Maple syrup urine disease

Answer

Hawkinsuria

Question 5

Inherited hyperammonemia is a result of deficiency of which enzyme of the Krebs-Henseleit urea cycle?

Accepted Answer

N-acetyl glutamate synthetase

Answer

Malate dehydrogenase

Answer

Isocitrate dehydrogenase

Answer

Succinate dehydrogenase

Question 6

A 2-month-old infant presents with poor feeding, vomiting, and lethargy. Laboratory studies show hyperammonemia and elevated levels of orotic acid in the urine. Which of the following is the most likely enzyme deficiency?

Accepted Answer

Ornithine transcarbamylase (OTC) deficiency

Answer

Orotidine 5′-phosphate decarboxylase deficiency

Answer

Carbamoyl phosphate synthetase I deficiency

Answer

Argininosuccinate lyase deficiency

Question 7

A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

Accepted Answer

Homogentisate oxidase

Answer

Fumarase

Answer

Tyrosinase

Answer

Branched-chain alpha-ketoacid dehydrogenase

Question 8

Nitric oxide is synthesized from which of the following amino acids?

Accepted Answer

Arginine

Answer

Tryptophan

Answer

Lysine

Answer

Tyrosine

Question 9

A patient has elevated phenylalanine levels (40 mg/dL), but phenylalanine hydroxylase enzyme levels are normal. Which cofactor deficiency is most likely responsible for this condition?

Accepted Answer

Tetrahydrobiopterin (BH4)

Answer

Tetrahydrofolate

Answer

Pyridoxine

Answer

Thiamine

Question 10

The image shows a biochemical pathway. Name the enzyme marked as X.

Accepted Answer

Creatine Kinase

Answer

Creatine Phosphorylase

Answer

Argininosuccinase

Answer

Ornithine transcarbamoylase

Amino Acid Metabolism — MCQs

Amino Acid Metabolism — MCQs

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