Amino Acid Metabolism — MCQs

A female neonate presented with lethargy at 24 hours of age, followed by focal seizure activity at 54 hours. A sepsis workup was negative. Her plasma ammonia level was found to be 1,000 mmol/L (normal 5-35 mmol/L). Quantitative plasma amino acid levels revealed a marked elevation of argininosuccinate. Which one of the following enzymic activities is most likely to be deficient in this patient?

Q324Medium

Which of the following amino acids is in order of increasing polarity: Alanine, Valine, Glycine, Isoleucine?

Q325Easy

Which of the following is a purely glucogenic amino acid?

Q326Easy

FIGLU is an intermediate in which metabolic pathway?

Q327Medium

A 16-year-old patient presents with recurrent joint pains, dark spots in the sclera, and blackening of urine on standing. What is the most probable diagnosis?

Q328Medium

Plasma levels of which of the following are likely to be lower than normal in a case of severe liver disease?

Q329Easy

Which condition is characterized by the smell of sweaty feet?

Q330Easy

Urea is formed in:

Amino Acid Metabolism Indian Medical PG Practice Questions and MCQs

Question 321: What biochemical substance supplies ammonia to the liver?

A. Arginine
B. Alanine (Correct Answer)
C. Lactate
D. Pyruvate

Explanation: **Explanation:** The correct answer is **Alanine**. This question tests the understanding of the **Cahill Cycle (Glucose-Alanine Cycle)**, which is the primary mechanism for transporting nitrogen from skeletal muscle to the liver. **Why Alanine is Correct:** During periods of muscle protein catabolism, amino groups are transferred to $\alpha$-ketoglutarate to form glutamate. In the muscle, the enzyme **Alanine Aminotransferase (ALT)** transfers this amino group from glutamate to pyruvate (a product of glycolysis), forming Alanine. Alanine is then released into the blood and travels to the liver. In the liver, ALT reverses the reaction, converting Alanine back into pyruvate and releasing **ammonia**, which enters the **Urea Cycle** for detoxification and excretion. **Why Other Options are Incorrect:** * **Arginine:** While Arginine is an intermediate in the Urea Cycle, it is not a primary transporter of ammonia from peripheral tissues to the liver. Its role is to be cleaved by arginase to produce urea and ornithine. * **Lactate:** Lactate is involved in the **Cori Cycle**, transporting carbon skeletons from muscle to liver for gluconeogenesis during anaerobic metabolism. It does not contain nitrogen and cannot supply ammonia. * **Pyruvate:** Pyruvate is a keto-acid that acts as the carbon skeleton for Alanine. It must be transaminated (receive an amino group) to become Alanine before it can transport nitrogen. **NEET-PG High-Yield Pearls:** * **Glutamine** is the primary transporter of ammonia from **most peripheral tissues** (especially the brain) to the liver/kidneys. * **Alanine** is the specific transporter of ammonia from **skeletal muscle** to the liver. * The Glucose-Alanine cycle serves a dual purpose: it detoxifies ammonia and provides a substrate (pyruvate) for **gluconeogenesis** in the liver. * Key Enzyme: **ALT (Alanine Aminotransferase)** requires **Pyridoxal Phosphate (Vitamin B6)** as a cofactor.

Question 322: Which of the following is NOT an aromatic amino acid?

A. Lysine (Correct Answer)
B. Phenylalanine
C. Tyrosine
D. Tryptophan

Explanation: ### Explanation **1. Why Lysine is the Correct Answer:** Aromatic amino acids are characterized by the presence of a **benzene ring** (phenyl group) or a related cyclic structure in their side chains. **Lysine** is a basic, aliphatic amino acid. Its side chain consists of a straight-chain hydrocarbon (butyl group) ending in a primary amino group ($\epsilon$-amino group). Because it lacks a ring structure, it is not classified as aromatic. **2. Analysis of Incorrect Options:** * **Phenylalanine (Option B):** This is a purely aromatic amino acid containing a phenyl ring attached to alanine. It is an essential amino acid and the precursor for tyrosine. * **Tyrosine (Option C):** This is a hydroxylated derivative of phenylalanine (contains a phenol group). It is technically "amphipathic" but classified as aromatic. It serves as a precursor for thyroxine, melanin, and catecholamines. * **Tryptophan (Option D):** This contains an **indole ring** (a benzene ring fused to a pyrrole ring). It is the most complex aromatic amino acid and serves as the precursor for serotonin, melatonin, and niacin (Vitamin B3). **3. NEET-PG High-Yield Clinical Pearls:** * **Absorbance:** Aromatic amino acids absorb UV light at **280 nm**. Tryptophan has the highest absorbance, followed by Tyrosine. This property is used for protein quantification. * **Essentiality:** Phenylalanine and Tryptophan are **essential**, while Tyrosine is **semi-essential** (it can be synthesized from phenylalanine). * **Metabolic Fate:** All three aromatic amino acids are **both glucogenic and ketogenic**. * **Special Tests:** The **Xanthoproteic test** is used to detect aromatic amino acids, yielding a yellow color upon reaction with concentrated nitric acid.

Question 323: A female neonate presented with lethargy at 24 hours of age, followed by focal seizure activity at 54 hours. A sepsis workup was negative. Her plasma ammonia level was found to be 1,000 mmol/L (normal 5-35 mmol/L). Quantitative plasma amino acid levels revealed a marked elevation of argininosuccinate. Which one of the following enzymic activities is most likely to be deficient in this patient?

A. Arginase
B. Argininosuccinate lyase (Correct Answer)
C. Argininosuccinate synthase
D. Carbamoyl phosphate synthetase I

Explanation: ### **Explanation** The clinical presentation of neonatal hyperammonemia (lethargy, seizures, and ammonia >1,000 mmol/L) after a 24-hour symptom-free interval is characteristic of a **Urea Cycle Disorder (UCD)**. **1. Why Argininosuccinate Lyase is Correct:** The definitive clue is the **marked elevation of argininosuccinate** in the plasma. In the urea cycle, **Argininosuccinate Lyase (ASL)** is responsible for cleaving argininosuccinate into **Arginine** and **Fumarate**. A deficiency in this enzyme (Argininosuccinic Aciduria) leads to a massive buildup of argininosuccinate, which is then excreted in the urine. It is the second most common UCD. **2. Why Other Options are Incorrect:** * **Arginase:** Deficiency leads to **Argininemia**. Unlike other UCDs, it typically presents later (infancy/childhood) with progressive spastic diplegia rather than acute neonatal hyperammonemia. * **Argininosuccinate Synthase:** Deficiency causes **Citrullinemia Type I**. It would result in a marked elevation of **Citrulline**, not argininosuccinate. * **Carbamoyl Phosphate Synthetase I (CPS-I):** This is a proximal urea cycle defect. It causes severe hyperammonemia but with **low levels** of citrulline and argininosuccinate, as the cycle is blocked at the very first step. **3. NEET-PG Clinical Pearls:** * **Argininosuccinic Aciduria** is unique because **Trichorrhexis nodosa** (fragile, node-like hair) is a classic physical finding in survivors. * **Treatment Tip:** Unlike other UCDs, supplementation with high-dose **Arginine** can often help "bypass" the cycle in ASL deficiency by promoting the excretion of nitrogen through argininosuccinate. * **Differential Diagnosis:** Always check **Orotic Acid** levels; if elevated with hyperammonemia, suspect **Ornithine Transcarbamylase (OTC) deficiency** (the most common UCD, X-linked).

Question 324: Which of the following amino acids is in order of increasing polarity: Alanine, Valine, Glycine, Isoleucine?

A. Isoleucine < Valine < Alanine < Glycine (Correct Answer)
B. Valine < Glycine < Alanine < Isoleucine
C. Alanine < Isoleucine < Glycine < Valine
D. Isoleucine < Alanine < Valine < Glycine

Explanation: ### Explanation **Concept: Hydrophobicity and Side-Chain Length** The polarity of non-polar (hydrophobic) amino acids is determined by the size and nature of their R-groups (side chains). In aliphatic amino acids, the longer the hydrocarbon chain, the more **hydrophobic** (less polar) the amino acid becomes. Conversely, the smaller the R-group, the less it interferes with water solubility, making it relatively more polar. * **Isoleucine:** Contains a branched four-carbon aliphatic side chain. It is the most hydrophobic/least polar of the group. * **Valine:** Contains a three-carbon branched side chain. It is less hydrophobic than isoleucine but more so than alanine. * **Alanine:** Contains a simple methyl group (-CH₃). * **Glycine:** The simplest amino acid with only a Hydrogen atom as its R-group. Because it lacks a hydrocarbon chain, it is the least hydrophobic (most polar) among the non-polar amino acids. **Analysis of Options:** * **Option A (Correct):** Correctly ranks them from the longest hydrocarbon chain (Isoleucine) to the shortest/none (Glycine). * **Options B, C, and D:** These are incorrect because they fail to follow the inverse relationship between hydrocarbon chain length and polarity. For example, placing Glycine anywhere but the end of an "increasing polarity" list is incorrect. **High-Yield Clinical Pearls for NEET-PG:** * **Glycine:** The only achiral amino acid (no asymmetric carbon). It is essential for the synthesis of Heme, Purines, Creatine, and Glutathione. * **Branched-Chain Amino Acids (BCAA):** Leucine, Isoleucine, and Valine. Their metabolism is impaired in **Maple Syrup Urine Disease (MSUD)** due to a deficiency in the Branched-chain alpha-keto acid dehydrogenase complex. * **Hydropathy Index:** Isoleucine has the highest hydropathy index, making it frequently buried in the hydrophobic core of globular proteins.

Question 325: Which of the following is a purely glucogenic amino acid?

A. Isoleucine
B. Tyrosine
C. Lysine
D. Proline (Correct Answer)

Explanation: **Explanation:** Amino acids are classified based on their metabolic end-products into three categories: **Purely Glucogenic**, **Purely Ketogenic**, and **Both (Mixed)**. **Why Proline is Correct:** Proline is a **purely glucogenic** amino acid. Its metabolism involves conversion to glutamate-γ-semialdehyde, which is then oxidized to **Glutamate**. Glutamate undergoes oxidative deamination to form **α-ketoglutarate**, a key intermediate of the TCA cycle. Since it enters the TCA cycle and can contribute to the net synthesis of glucose via gluconeogenesis, it is classified as purely glucogenic. **Analysis of Incorrect Options:** * **Isoleucine:** This is a **mixed (both)** amino acid. Its catabolism yields both Succinyl-CoA (glucogenic) and Acetyl-CoA (ketogenic). * **Tyrosine:** This is also a **mixed** amino acid. It is a precursor to both Fumarate (glucogenic) and Acetoacetate (ketogenic). Other mixed amino acids include Phenylalanine, Tryptophan, and Threonine. * **Lysine:** Along with Leucine, Lysine is one of the two **purely ketogenic** amino acids. They are degraded exclusively to Acetyl-CoA or Acetoacetate and cannot be used for glucose synthesis. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Purely Ketogenic:** "The L's" – **L**eucine and **L**ysine. * **Mnemonic for Mixed (Both):** "PITT" – **P**henylalanine, **I**soleucine, **T**yrosine, **T**ryptophan (and Threonine). * **Glucogenic count:** Out of the 20 standard amino acids, 14 are purely glucogenic, 2 are purely ketogenic, and 4 are both. * **Clinical Correlation:** In states of starvation or uncontrolled Diabetes Mellitus, glucogenic amino acids are the primary substrates for maintaining blood glucose levels.

Question 326: FIGLU is an intermediate in which metabolic pathway?

A. Valine metabolism
B. Histidine metabolism (Correct Answer)
C. Methionine metabolism
D. Arginine metabolism

Explanation: **Explanation:** **Histidine metabolism** is the correct answer because FIGLU (**Formiminoglutamate**) is a key intermediate in the catabolism of Histidine to Glutamate. 1. **The Pathway:** Histidine is first converted to urocanate by the enzyme histidase. After a series of steps, it forms FIGLU. The formimino group of FIGLU is then transferred to **Tetrahydrofolate (THF)** by the enzyme *formiminotransferase*, resulting in the formation of Glutamate and $N^5$-formimino-THF. 2. **Clinical Significance:** Since THF is required to clear FIGLU, a deficiency in **Folic Acid** leads to the accumulation and increased urinary excretion of FIGLU. This forms the basis of the **FIGLU Excretion Test** (Histidine loading test) used to diagnose folate deficiency. **Why other options are incorrect:** * **Valine metabolism:** Valine is a branched-chain amino acid (BCAA) that is metabolized into Succinyl-CoA via Methylmalonyl-CoA. * **Methionine metabolism:** Methionine is converted to S-adenosylmethionine (SAM) and eventually Homocysteine. It is linked to the folate cycle but does not produce FIGLU. * **Arginine metabolism:** Arginine is converted to Urea and Ornithine in the urea cycle, or used to produce Nitric Oxide and Creatine. **High-Yield Clinical Pearls for NEET-PG:** * **Histidinemia:** Caused by a deficiency of the enzyme **Histidase**. It is a relatively benign condition but can be associated with mental retardation. * **Folate Trap:** FIGLU levels rise in B12 deficiency as well, because B12 is needed to recycle THF, but FIGLU is specifically used as a functional marker for **Folate status**. * **Mnemonic:** "Histidine goes to Glutamate via FIGLU."

Question 327: A 16-year-old patient presents with recurrent joint pains, dark spots in the sclera, and blackening of urine on standing. What is the most probable diagnosis?

A. Alkaptonuria (Correct Answer)
B. Tyrosinemia
C. Phenylketonuria
D. All of the above

Explanation: **Explanation:** The clinical presentation of dark urine on standing, scleral pigmentation, and joint pain is the classic triad of **Alkaptonuria**, an autosomal recessive disorder of phenylalanine and tyrosine metabolism. **1. Why Alkaptonuria is correct:** The condition is caused by a deficiency of the enzyme **Homogentisate Oxidase**, leading to the accumulation of **Homogentisic Acid (HGA)**. * **Dark Urine:** When urine is exposed to air (standing), HGA is oxidized to benzoquinone acetate, which polymerizes into a black pigment (alkapton). * **Ochronosis:** Over time, this pigment deposits in connective tissues, causing dark spots in the sclera and ears. * **Arthritis:** Pigment deposition in large joints leads to ochronotic arthritis, typically manifesting in the teens or early adulthood. **2. Why other options are incorrect:** * **Tyrosinemia:** Presents primarily with liver failure (Type I), cabbage-like odor, or palmoplantar keratosis (Type II). It does not cause blackening of urine. * **Phenylketonuria (PKU):** Characterized by intellectual disability, seizures, and a "mousy" body odor due to phenylacetate. Patients often have fair skin and blue eyes (hypopigmentation), not hyperpigmentation. **High-Yield Clinical Pearls for NEET-PG:** * **Enzyme Defect:** Homogentisate 1,2-dioxygenase. * **Diagnostic Test:** Ferric chloride test (turns urine deep blue/green) and Silver nitrate test. * **Radiology:** "Bamboo spine" appearance due to calcification of intervertebral discs (mimics Ankylosing Spondylitis). * **Management:** Low protein diet (restriction of Phenylalanine and Tyrosine) and **Nitisinone**, which inhibits the formation of HGA.

Question 328: Plasma levels of which of the following are likely to be lower than normal in a case of severe liver disease?

A. NH3
B. NH4+
C. Urea (Correct Answer)
D. Alanine

Explanation: **Explanation:** The liver is the primary site for the **Urea Cycle (Ornithine Cycle)**, the metabolic pathway responsible for converting toxic ammonia (NH₃) into non-toxic urea for excretion by the kidneys. **Why Urea is the Correct Answer:** In severe liver disease (such as cirrhosis or fulminant hepatic failure), the hepatocytes are damaged, leading to a significant impairment of the urea cycle enzymes. Consequently, the liver cannot efficiently convert ammonia into urea. This results in a **decrease in plasma urea levels** (often reflected as a low Blood Urea Nitrogen - BUN) and a reciprocal increase in toxic nitrogenous waste products. **Analysis of Incorrect Options:** * **A & B (NH₃ and NH₄⁺):** Because the liver cannot convert ammonia into urea, ammonia levels **increase** in the blood. This hyperammonemia is a hallmark of liver failure and is the primary driver of hepatic encephalopathy. * **D (Alanine):** Alanine is a major gluconeogenic amino acid that carries nitrogen from muscles to the liver. In liver disease, the liver's ability to uptake and metabolize amino acids for gluconeogenesis is impaired, typically leading to **elevated** or normal plasma levels of aromatic and certain other amino acids, not a decrease. **High-Yield Clinical Pearls for NEET-PG:** * **BUN/Creatinine Ratio:** A very low BUN in the presence of normal creatinine often points toward severe liver dysfunction or malnutrition. * **Hyperammonemia:** Leads to increased brain **Glutamine** levels (via glutamine synthetase in astrocytes), causing osmotic swelling and cerebral edema. * **Deficiency Sign:** The most common urea cycle enzyme deficiency is **Ornithine Transcarbamoylase (OTC) deficiency** (X-linked), which also presents with low urea and high ammonia.

Question 329: Which condition is characterized by the smell of sweaty feet?

A. Maple syrup urine disease (MSUD)
B. Phenylketonuria
C. Homocystinuria
D. Glutaric acidemia (Correct Answer)

Explanation: ### Explanation The correct answer is **Glutaric acidemia (specifically Type II)**. #### 1. Why Glutaric Acidemia is Correct Glutaric acidemia Type II (Multiple Acyl-CoA Dehydrogenase Deficiency) is a metabolic disorder where the body cannot properly process certain fats and proteins. This leads to the accumulation of organic acids, specifically **isovaleric and glutaric acids**. The characteristic **"sweaty feet" odor** is primarily attributed to the accumulation of **isovaleric acid**. Note: While Isovaleric acidemia is the classic cause of this odor, Glutaric acidemia Type II presents similarly due to the shared metabolic pathway disruption. #### 2. Why Other Options are Incorrect * **A. Maple syrup urine disease (MSUD):** Caused by a deficiency in the Branched-Chain Alpha-Keto Acid Dehydrogenase complex. It is characterized by a **burnt sugar or maple syrup** odor in the urine. * **B. Phenylketonuria (PKU):** Caused by a deficiency of Phenylalanine Hydroxylase. It is characterized by a **mousy or musty** odor. * **C. Homocystinuria:** A defect in cystathionine beta-synthase. It does not typically present with a specific diagnostic odor but is associated with marfanoid habitus and ectopia lentis. #### 3. High-Yield Clinical Pearls for NEET-PG Memorizing characteristic odors is essential for metabolic biochemistry questions: * **Sweaty Feet:** Isovaleric acidemia, Glutaric acidemia Type II. * **Mousy/Musty:** Phenylketonuria (PKU). * **Maple Syrup/Burnt Sugar:** MSUD. * **Rotten Fish:** Trimethylaminuria. * **Cabbage-like/Rancid Butter:** Tyrosinemia Type I. * **Swimming Pool odor:** Hawkinsinuria. * **Boiled Cabbage:** Hypermethioninemia.

Question 330: Urea is formed in:

A. Brain
B. Kidney
C. Liver (Correct Answer)
D. Intestine

Explanation: **Explanation:** The **Liver** is the primary site for the urea cycle (Ornithine cycle) because it is the only organ that expresses all the necessary enzymes in significant quantities. Specifically, the enzyme **Arginase**, which catalyzes the final step of cleaving Arginine into Urea and Ornithine, is almost exclusively found in the liver. This process is vital for detoxifying ammonia—a neurotoxic byproduct of protein catabolism—by converting it into water-soluble urea for excretion. **Why other options are incorrect:** * **Brain:** While the brain produces ammonia, it lacks the full complement of urea cycle enzymes. It detoxifies ammonia primarily by converting it to **Glutamine** via Glutamine Synthetase. * **Kidney:** The kidney is responsible for the **excretion** of urea, not its synthesis. While it can synthesize small amounts of Arginine, it lacks sufficient Arginase to complete the urea cycle. * **Intestine:** The intestine participates in nitrogen metabolism (producing ammonia via bacterial action), but it does not possess the enzymatic machinery to produce urea. **High-Yield Clinical Pearls for NEET-PG:** * **Rate-limiting step:** Carbamoyl Phosphate Synthetase I (CPS-I), which requires **N-acetylglutamate (NAG)** as an essential allosteric activator. * **Subcellular location:** The cycle is "split"; the first two steps occur in the **Mitochondria**, while the remaining steps occur in the **Cytosol**. * **Hyperammonemia:** Deficiency of any urea cycle enzyme leads to ammonia toxicity. **Ornithine Transcarbamoylase (OTC) deficiency** is the most common urea cycle disorder and is X-linked recessive. * **BUN (Blood Urea Nitrogen):** Levels rise in renal failure (Azotemia) but decrease in severe liver disease due to impaired synthesis.

Practice by Chapter

Protein Digestion and Absorption

Practice Questions

Transamination and Deamination

Practice Questions

Urea Cycle

Practice Questions

Disorders of Urea Cycle

Practice Questions

Metabolism of Individual Amino Acids

Practice Questions

Inborn Errors of Amino Acid Metabolism

Practice Questions

Phenylketonuria and Alkaptonuria

Practice Questions

Homocystinuria and Methionine Metabolism

Practice Questions

Synthesis of Biologically Important Compounds from Amino Acids

Practice Questions

Nitrogen Balance

Practice Questions

Ammonia Metabolism and Toxicity

Practice Questions

One-Carbon Transfer Reactions

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free