Amino Acid Metabolism Practice Questions

Q: In urea cycle disorder, which of the following substances can be used to reduce the levels of ammonia?

Phenylbutyrate. **Explanation:** In **Urea Cycle Disorders (UCDs)**, the body lacks the enzymes necessary to convert toxic ammonia into urea for excretion. This leads to hyperammonemia, which is neurotoxic. **Why Phenylbutyrate is correct:** Sodium phenylbutyrate acts as an **ammonia scavenger**. Once ingested, it is rapidly metabolized into phenylacetate. Phenylacetate conjugates with **glutamine** (which contains two nitrogen atoms) to form phenylacetylglutamine, which is then excreted by the kidneys. By removing glutamine, the body is forced to use ammonia to synthesize more glutamine, thereby effectively lowering circulating ammonia levels through an alternative pathway. **Analysis of Incorrect Options:** * **L-carnitine:** While used in organic acidemias to conjugate with organic acids, it does not directly lower ammonia in primary urea cycle defects. * **Isoleucine:** This is a branched-chain amino acid. While protein restriction (including essential amino acids) is managed in UCDs, isoleucine itself does not reduce ammonia levels. * **Glutamate:** Adding glutamate would be counterproductive. In hyperammonemia, ammonia combines with glutamate to form glutamine; adding more substrate does not aid excretion and may contribute to the nitrogen load. **NEET-PG High-Yield Pearls:** * **Drug of Choice:** Sodium Phenylbutyrate and Sodium Benzoate (conjugates with Glycine) are the mainstays for chronic management of UCDs. * **Most Common UCD:** Ornithine Transcarbamylase (OTC) deficiency (the only X-linked UCD). * **Acute Management:** In severe neonatal hyperammonemia, **hemodialysis** is the most effective method to rapidly reduce ammonia levels. * **Dietary Rule:** High-calorie, low-protein diet is essential to prevent catabolism.

Q: Xanthurenic acid, the accumulation of which occurs due to pyridoxine deficiency, is a metabolite of which amino acid?

Tryptophan. **Explanation:** The correct answer is **Tryptophan**. **Why Tryptophan is correct:** Tryptophan is metabolized via the **Kynurenine pathway** to produce Niacin (Vitamin B3). A critical step in this pathway involves the conversion of 3-hydroxykynurenine to 3-hydroxyanthranilic acid, catalyzed by the enzyme **Kynureninase**. This enzyme requires **Pyridoxal Phosphate (PLP)**, the active form of Vitamin B6, as a cofactor. In **Pyridoxine (B6) deficiency**, kynureninase activity is impaired. As a result, 3-hydroxykynurenine cannot be converted further down the niacin pathway and is instead shunted toward an alternative metabolic route, leading to the excessive formation and urinary excretion of **Xanthurenic acid**. **Why other options are incorrect:** * **Tyrosine & Phenylalanine:** These are precursors to catecholamines (Dopamine, Epinephrine), Melanin, and Thyroxine. Their metabolism involves enzymes like Phenylalanine hydroxylase and p-hydroxyphenylpyruvate hydroxylase, but they do not produce xanthurenic acid. * **Alanine:** This is a non-essential amino acid primarily involved in the Glucose-Alanine cycle (Cahill cycle) for transporting nitrogen to the liver. Its transamination requires B6, but it does not lead to xanthurenic acid formation. **High-Yield Clinical Pearls for NEET-PG:** * **Xanthurenic Acid Index:** The measurement of xanthurenic acid in urine after a tryptophan load test is a sensitive indicator of **Vitamin B6 deficiency**. * **Niacin Link:** Since Tryptophan is a precursor to Niacin, a B6 deficiency can secondary lead to **Pellagra-like symptoms** because the kynurenine pathway is blocked. * **Hartnup Disease:** A defect in the transport of neutral amino acids (like Tryptophan) can also lead to niacin deficiency and pellagra symptoms.

Q: Phenylketonuria I is due to deficiency of which enzyme?

Phenylalanine hydroxylase. **Explanation:** **Phenylketonuria (PKU) Type I**, also known as Classical PKU, is an autosomal recessive disorder caused by a deficiency of the enzyme **Phenylalanine hydroxylase (PAH)**. 1. **Why Option A is correct:** Under normal physiological conditions, PAH converts the essential amino acid Phenylalanine into Tyrosine. This reaction requires the cofactor **Tetrahydrobiopterin (BH4)**. A deficiency in PAH leads to the accumulation of Phenylalanine in the blood and tissues, which is then alternatively metabolized into phenylketones (like phenylpyruvate), causing neurotoxicity and intellectual disability. 2. **Why other options are incorrect:** * **Option B (Homogentisate oxidase):** Deficiency of this enzyme leads to **Alkaptonuria**, characterized by ochronosis (darkening of tissues) and urine that turns black upon standing. * **Option C (Tyrosinase):** Deficiency of tyrosinase leads to **Oculocutaneous Albinism**, as this enzyme is critical for converting tyrosine into melanin. * **Note on PKU Type II & III:** These are "Malignant PKU" caused by a deficiency in **Dihydrobiopterin reductase** or enzymes synthesizing BH4, rather than the PAH enzyme itself. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Intellectual disability, "mousy" or musty body odor (due to phenylacetic acid), and hypopigmentation (fair skin/blue eyes) because tyrosine is a precursor to melanin. * **Diagnosis:** Guthrie Test (bacterial inhibition assay) or Tandem Mass Spectrometry. * **Management:** Dietary restriction of Phenylalanine and supplementation of Tyrosine (which becomes an "essential" amino acid in PKU patients). * **Maternal PKU:** If a pregnant woman with PKU doesn't maintain a strict diet, the high phenylalanine levels act as a teratogen, causing microcephaly and congenital heart defects in the fetus.

Q: Hyperammonemia inhibits the TCA cycle by depleting which intermediate?

α-ketoglutarate. **Explanation:** The primary mechanism by which hyperammonemia inhibits the TCA cycle is through the **depletion of α-ketoglutarate**. When blood ammonia ($NH_3$) levels rise, the body attempts to detoxify it, particularly in the brain. This occurs via two sequential reactions: 1. **Reductive Amination:** Ammonia reacts with **α-ketoglutarate** to form Glutamate, catalyzed by *Glutamate Dehydrogenase*. 2. **Glutamine Synthesis:** Glutamate further reacts with another molecule of ammonia to form Glutamine, catalyzed by *Glutamine Synthetase*. Because α-ketoglutarate is a vital intermediate of the TCA cycle, its excessive consumption to "mop up" ammonia leads to its depletion. This halts the TCA cycle, resulting in a failure of aerobic respiration and a subsequent **ATP deficit** in neurons, which manifests as encephalopathy. **Analysis of Incorrect Options:** * **Oxaloacetate:** While it can be converted to Aspartate via transamination, it is not the primary substrate consumed during acute ammonia detoxification. * **Citrate:** This is the product of the first step of the TCA cycle; its levels fall secondary to the lack of α-ketoglutarate and slowed cycle turnover, but it is not the direct target of depletion. * **Succinyl CoA:** This is a downstream intermediate. Its levels decrease as a consequence of the cycle's failure, not as the primary cause. **NEET-PG High-Yield Pearls:** * **Brain's main detoxification route:** Glutamine synthesis (this causes osmotic swelling of astrocytes, leading to cerebral edema). * **Key Enzyme inhibited:** High ammonia also inhibits the **α-ketoglutarate dehydrogenase** complex directly. * **Clinical Presentation:** Asterixis (flapping tremors), altered sensorium, and elevated blood lactate (due to shifted metabolism toward glycolysis).

Q: Which amino acid undergoes hepatic deamination?

Glutamate. **Explanation:** The correct answer is **Glutamate**. In amino acid metabolism, the primary mechanism for removing nitrogen is a two-step process: **Transamination** followed by **Oxidative Deamination**. 1. **Why Glutamate is Correct:** Most amino acids transfer their $\alpha$-amino group to $\alpha$-ketoglutarate via transamination, forming **Glutamate**. Glutamate then acts as a "collection center" for amino groups. In the liver mitochondria, Glutamate undergoes rapid **oxidative deamination** catalyzed by the enzyme **Glutamate Dehydrogenase (GDH)**. This reaction releases free ammonia ($NH_3$), which enters the Urea Cycle for detoxification. Glutamate is the only amino acid that undergoes oxidative deamination at a significant rate in mammalian tissues. 2. **Why Other Options are Incorrect:** * **Alanine:** It is the primary carrier of nitrogen from muscles to the liver (Glucose-Alanine cycle). However, it must first be transaminated to Glutamate before the nitrogen can be released. * **Aspartate:** It participates in the Urea Cycle by providing the second nitrogen atom (reacting with Citrulline), but it does not undergo direct deamination to release free ammonia. * **Glycine:** While glycine can be broken down by the Glycine Cleavage System, it is not the primary substrate for hepatic deamination in the context of the general nitrogen pool. **High-Yield NEET-PG Pearls:** * **Glutamate Dehydrogenase (GDH):** It is unique because it can use either $NAD^+$ or $NADP^+$ as a coenzyme. * **Allosteric Regulation:** GDH is inhibited by **ATP/GTP** (high energy) and activated by **ADP/GDP** (low energy). * **Transdeamination:** The combined action of Aminotransferases and GDH is termed "Transdeamination," which is the major pathway for the catabolism of amino acids.

Q: What is the chemical process involved in the conversion of noradrenaline to adrenaline?

Methylation. **Explanation:** The conversion of **Noradrenaline to Adrenaline** is the final step in the catecholamine biosynthetic pathway. This reaction is a **Methylation** process catalyzed by the enzyme **Phenylethanolamine N-methyltransferase (PNMT)**. 1. **Why Methylation is Correct:** In this reaction, a methyl group (–CH₃) is transferred from **S-adenosylmethionine (SAM)**, which acts as the universal methyl donor, to the nitrogen atom of noradrenaline. This N-methylation increases the lipophilicity of the molecule, allowing it to act on different adrenergic receptors (primarily β-receptors). 2. **Why Other Options are Incorrect:** * **Hydroxylation:** This occurs earlier in the pathway (e.g., Phenylalanine to Tyrosine by Phenylalanine hydroxylase, or Tyrosine to DOPA by Tyrosine hydroxylase). * **Carboxylation:** This involves adding CO₂. In catecholamine synthesis, the opposite occurs: **Decarboxylation** (DOPA to Dopamine). * **Dehydrogenation:** This involves the removal of hydrogen (redox reaction), which is not the mechanism for this specific conversion. **High-Yield Clinical Pearls for NEET-PG:** * **Rate-limiting step:** Tyrosine hydroxylase is the rate-limiting enzyme for catecholamine synthesis. * **Glucocorticoid Influence:** PNMT is induced by **cortisol**. This is why the adrenal medulla (where noradrenaline is converted to adrenaline) is anatomically surrounded by the adrenal cortex. * **Location:** While noradrenaline is the primary neurotransmitter in sympathetic postganglionic neurons, adrenaline is primarily produced in the **adrenal medulla**. * **Cofactor:** Always remember **SAM** is the donor for this methylation; Vitamin B12 and Folate are indirectly required to regenerate SAM.

Q: In alkaptonuria, what substance is found in the urine?

Homogentisic acid. **Explanation:** **Alkaptonuria** is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme **homogentisate 1,2-dioxygenase**. This enzyme is essential in the catabolic pathway of the aromatic amino acids **phenylalanine and tyrosine**. 1. **Why Homogentisic Acid is Correct:** Due to the enzyme deficiency, the body cannot break down homogentisic acid (HGA). Consequently, HGA accumulates in the blood and is excreted in large quantities in the **urine**. Upon standing or exposure to air, HGA undergoes oxidation and polymerization to form a melanin-like pigment, causing the urine to turn **dark or black**. 2. **Why Incorrect Options are Wrong:** * **Phenylalanine:** Elevated in Phenylketonuria (PKU) due to phenylalanine hydroxylase deficiency, not alkaptonuria. * **Ketones:** Found in the urine (ketonuria) during diabetic ketoacidosis, starvation, or prolonged fasting. * **Acetates:** These are common metabolic intermediates but are not specific diagnostic markers for amino acid metabolism disorders like alkaptonuria. **High-Yield Clinical Pearls for NEET-PG:** * **Ochronosis:** The deposition of black pigment in connective tissues, cartilage (blue-black ears), and sclera. * **Arthritis:** Chronic accumulation of HGA in joints leads to severe, early-onset large-joint arthritis and intervertebral disc calcification. * **Diagnostic Test:** The addition of an alkali (like KOH) to the urine sample will rapidly darken it. It also gives a **false-positive** result with Benedict’s test (reducing property). * **Treatment:** Low protein diet (restricting Phenylalanine/Tyrosine) and **Nitisinone**, which inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase to reduce HGA production.

Question 1

An 8-year-old child presents with tall stature, long limbs, scoliosis, pectus carinatum, ectopia lentis, and a history of recurrent thromboembolic events. He shows improvement with pharmacologic doses of vitamin B6. Which enzyme is most likely deficient in this child?

Accepted Answer

Cystathionine beta-synthase

Answer

S-Adenosylhomocysteine hydrolase

Answer

Methionine synthase

Answer

N5,N10-Methylenetetrahydrofolate reductase

Question 2

In urea cycle disorder, which of the following substances can be used to reduce the levels of ammonia?

Accepted Answer

Phenylbutyrate

Answer

L-carnitine

Answer

Isoleucine

Answer

Glutamate

Question 3

A 40-year-old woman presents with progressive palmoplantar pigmentation. X-ray of the spine shows calcification of intervertebral discs. On adding Benedict's reagent to her urine, a greenish-brown precipitate forms, and the supernatant fluid appears blue-black. What is the diagnosis?

Accepted Answer

Alkaptonuria

Answer

Phenylketonuria

Answer

Tyrosinemia type-2

Answer

Argininosuccinic aciduria

Question 4

Xanthurenic acid, the accumulation of which occurs due to pyridoxine deficiency, is a metabolite of which amino acid?

Accepted Answer

Tryptophan

Answer

Tyrosine

Answer

Phenylalanine

Answer

Alanine

Question 5

Phenylketonuria I is due to deficiency of which enzyme?

Accepted Answer

Phenylalanine hydroxylase

Answer

Homogentisate oxidase

Answer

Tyrosinase

Answer

None of the above

Question 6

Hyperammonemia inhibits the TCA cycle by depleting which intermediate?

Accepted Answer

α-ketoglutarate

Answer

Oxaloacetate

Answer

Citrate

Answer

Succinyl CoA

Question 7

A 6-year-old child presents with mental retardation, failure to walk, failure to grow, seizures, hyperactivity, and tremors. Examination reveals microcephaly, fair hair, light skin color, and blue eyes. Which enzyme is deficient in this child?

Accepted Answer

Phenylalanine hydroxylase

Answer

Homogentisate dioxygenase

Answer

Tyrosinase

Answer

Fumaryl acetoacetate hydroxylase

Question 8

Which amino acid undergoes hepatic deamination?

Accepted Answer

Glutamate

Answer

Alanine

Answer

Aspartate

Answer

Glycine

Question 9

What is the chemical process involved in the conversion of noradrenaline to adrenaline?

Accepted Answer

Methylation

Answer

Hydroxylation

Answer

Carboxylation

Answer

Dehydrogenation

Question 10

In alkaptonuria, what substance is found in the urine?

Accepted Answer

Homogentisic acid

Answer

Phenylalanine

Answer

Ketones

Answer

Acetates

Amino Acid Metabolism — MCQs

Amino Acid Metabolism — MCQs

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