Q.1 – Which of the following is a common compound shared by the TCA (Tricarboxylic Acid) cycle and the Urea cycle?
A. α-Ketoglutarate
B. Succinyl-CoA
C. Oxaloacetate
D. Fumarate
E. Citrate
Correct Answer: D. Fumarate
Explanation: Fumarate is a key intermediate shared between the TCA and Urea cycles. In the Urea cycle, fumarate is produced during the conversion of argininosuccinate to arginine. Fumarate can then enter the TCA cycle as part of metabolic integration.
Incorrect Options:
A. α-Ketoglutarate: While a TCA intermediate, α-ketoglutarate is not involved in the Urea cycle.
B. Succinyl-CoA: This is a TCA intermediate involved in energy production but is not shared with the Urea cycle.
C. Oxaloacetate: Another TCA intermediate, primarily involved in gluconeogenesis and not directly linked to the Urea cycle.
E. Citrate: A TCA intermediate, but it does not play a role in the Urea cycle or its intermediates.
Q.2 – Which of the following is a common nitrogen acceptor for all reactions involving transaminases?
A. α-Ketoglutarate
B. Pyruvate
C. Oxaloacetate
D. Acetoacetate
E. Glutamate
Correct Answer: A. α-Ketoglutarate
Explanation: α-Ketoglutarate is a central nitrogen acceptor in transamination reactions. It accepts an amino group from various amino acids, forming glutamate. This reaction is crucial for amino acid metabolism and the recycling of nitrogen in metabolic pathways.
Incorrect Options:
B. Pyruvate: While pyruvate can act as an acceptor in specific cases (e.g., forming alanine), it is not the universal nitrogen acceptor in transaminase reactions.
C. Oxaloacetate: Functions as a substrate in certain transamination reactions (e.g., forming aspartate) but is not the common nitrogen acceptor.
D. Acetoacetate: A ketone body not involved in transamination reactions or nitrogen metabolism.
E. Glutamate: Glutamate is the product of the transamination reaction when α-ketoglutarate accepts an amino group, not the acceptor itself.
Q.3- A 55-year-old man diagnosed with cirrhosis of the liver is unable to detoxify ammonia, which can damage the brain. Which of the following amino acids can covalently bind ammonia, transport it, and store it in a non-toxic form?
A. Alanine
B. Aspartate
C. Cysteine
D. Glutamate
E. Serine
Correct Answer: D. Glutamate
Explanation: Glutamate can covalently bind ammonia to form glutamine through the action of glutamine synthetase. Glutamine is a non-toxic transport form of ammonia, which can travel safely in the bloodstream to the liver or kidneys for excretion or further metabolism.
Incorrect Options:
A. Alanine: While alanine plays a role in the glucose-alanine cycle for transporting nitrogen, it does not directly bind ammonia for detoxification.
B. Aspartate: Involved in nitrogen metabolism and the Urea cycle but does not serve as a direct ammonia transporter.
C. Cysteine: A sulfur-containing amino acid, not involved in binding or transporting ammonia.
E. Serine: Although serine participates in various metabolic reactions, it does not bind ammonia for detoxification.
Q.4- A newborn presenting with refusal to feed and irritability is diagnosed with a deficiency of cystathionine β-synthase. Which of the following compounds is expected to be elevated in the blood?
A. Glutamate
B. Homocysteine
C. Methionine
D. Serine
E. Valine
Correct Answer: B. Homocysteine
Explanation: Cystathionine β-synthase is an enzyme that converts homocysteine to cystathionine in the transsulfuration pathway. A deficiency of this enzyme leads to an accumulation of homocysteine in the blood, causing hyperhomocysteinemia, which is associated with metabolic disturbances and clinical symptoms.
Incorrect Options:
A. Glutamate: An important amino acid involved in various metabolic pathways but not directly linked to this deficiency.
C. Methionine: While methionine levels may increase in some cases, the primary and more significant elevation occurs in homocysteine.
D. Serine: A substrate in the transsulfuration pathway but not expected to accumulate in this condition.
E. Valine: A branched-chain amino acid unrelated to the pathway involving cystathionine β-synthase.
Q.5 – A 3-month-old child is being evaluated for vomiting and an episode of convulsions. Laboratory results reveal hyperammonemia and orotic aciduria. Which of the following enzyme defects is most likely to be present?
A. Arginase
B. Argininosuccinate synthetase
C. Glutaminase
D. Ornithine Transcarbamoylase
E. Urease
Correct Answer: D. Ornithine Transcarbamoylase
Explanation: A deficiency of ornithine transcarbamoylase (OTC), an enzyme in the urea cycle, leads to the accumulation of carbamoyl phosphate, which spills into the pyrimidine synthesis pathway, causing orotic aciduria. Hyperammonemia results from impaired urea cycle function.
Incorrect Options:
A. Arginase: Arginase deficiency causes hyperammonemia but does not result in orotic aciduria.
B. Argininosuccinate synthetase: Deficiency leads to hyperammonemia but not orotic aciduria, as carbamoyl phosphate does not accumulate.
C. Glutaminase: Not involved in the urea cycle and unlikely to explain the laboratory findings.
E. Urease: Urease is not an enzyme in human metabolism but a bacterial enzyme, irrelevant to this condition.
Q.6- Which of the following amino acids is not converted to succinyl-CoA during metabolism?
A. Threonine
B. Histidine
C. Isoleucine
D. Methionine
E. Valine
Correct Answer: B. Histidine
Explanation: Histidine is not metabolized into succinyl-CoA. Instead, it is converted to glutamate through a series of reactions. Glutamate is further catabolized to α-ketoglutarate, which enters the TCA cycle but does not contribute directly to Succinyl-CoA production.
Incorrect Options:
A. Threonine: Catabolized into pyruvate and succinyl-CoA
C. Isoleucine: Catabolized into Succinyl-CoA and acetyl-CoA, making it one of the amino acids directly linked to Succinyl-CoA formation.
D. Methionine: Converted into succinyl-CoA through intermediate steps, including the formation of homocysteine and methylmalonyl-CoA.
E. Valine: Also metabolized to Succinyl-CoA via the branched-chain amino acid degradation pathway.
Q.7 – A 30-year-old woman presents with symptoms of fatigue, irritability, and a recent history of photosensitive dermatitis. Upon investigation, she is diagnosed with Hartnup disease, caused by a deficiency of the transporter responsible for the absorption of the amino acid tryptophan. Tryptophan is a precursor for many compounds, deficiencies of which can cause such symptoms. Which of the following compounds is not synthesized from tryptophan?
A. Epinephrine
B. Indican
C. Melatonin
D. Niacin
E. Serotonin
Correct Answer: A. Epinephrine
Explanation: Epinephrine is not synthesized from tryptophan. Instead, it is derived from tyrosine through the catecholamine biosynthesis pathway and is unrelated to tryptophan metabolism.
Incorrect Options:
B. Indican: A metabolite formed from tryptophan degradation in the gut. In Hartnup disease, unabsorbed tryptophan is metabolized by intestinal bacteria to indole, which is converted to indican in the liver and excreted in urine.
C. Melatonin: Synthesized from serotonin, a product of tryptophan metabolism. Melatonin regulates sleep-wake cycles.
D. Niacin: Derived from tryptophan via the kynurenine pathway. Niacin is vital for NAD+ and NADP+ synthesis.
E. Serotonin: Directly synthesized from tryptophan and plays a key role in mood regulation.
Q.8 – Histamine, a chemical mediator involved in allergies and anaphylaxis, is synthesized from the amino acid histidine by which of the following processes?
A. Deamination
B. Decarboxylation
C. Dehydrogenation
D. Transamination
E. Hydroxylation
Correct Answer: B. Decarboxylation
Explanation: Histamine is synthesized from histidine through a decarboxylation reaction, which removes the carboxyl group (-COOH) from histidine, forming histamine. This reaction is catalyzed by the enzyme histidine decarboxylase, with pyridoxal phosphate (PLP) as a coenzyme.
Incorrect Options:
A. Deamination: Refers to removing an amino group (-NH2) from an amino acid that is not involved in histamine synthesis.
C. Dehydrogenation: This involves removing hydrogen atoms, typically seen in oxidation reactions, and is unrelated to histamine synthesis.
D. Transamination: Refers to the transfer of an amino group from one amino acid to a keto acid, not the process used for histamine formation.
E. Hydroxylation: Involves adding a hydroxyl group (-OH), as seen in the synthesis of other compounds like tyrosine derivatives, but not in histamine synthesis.
Q.9 – The synthesis of all of the following compounds, except one, is deficient in a patient suffering from Phenylketonuria (PKU). Which one is not affected?
A. Catecholamines
B. Melanin
C. Melatonin
D. Thyroid hormone
Correct Answer: C. Melatonin
Explanation: Melatonin synthesis is not affected in Phenylketonuria (PKU). Melatonin is derived from tryptophan via serotonin, and its pathway does not involve phenylalanine or tyrosine. Therefore, PKU, which disrupts phenylalanine metabolism, has no impact on melatonin production.
Incorrect Options:
A. Catecholamines: PKU leads to a deficiency in tyrosine, the precursor for catecholamines like dopamine, epinephrine, and norepinephrine.
B. Melanin: Tyrosine is also a precursor for melanin synthesis. In PKU, decreased tyrosine results in hypopigmentation due to reduced melanin production.
D. Thyroid hormone: Tyrosine is a precursor for thyroid hormones (T3 and T4). PKU-related tyrosine deficiency can affect thyroid hormone synthesis.
Q.10 – Which of the following amino acids should be low in the diet of a child suffering from Maple Syrup Urine Disease (an amino acid disorder)?
A. Branched-chain amino acids
B. Methionine
C. Phenylalanine
D. Tryptophan
E. Tyrosine
Correct Answer: A. Branched-chain amino acids.
Explanation: Maple Syrup Urine Disease (MSUD) is caused by a defect in the branched-chain α-keto acid dehydrogenase complex, which impairs the metabolism of branched-chain amino acids: leucine, isoleucine, and valine. A diet low in these amino acids is essential to prevent toxic accumulation and associated symptoms such as neurological damage and the characteristic sweet-smelling urine.
Incorrect Options:
B. Methionine: Methionine metabolism is unaffected in MSUD, and its restriction is not required.
C. Phenylalanine: Phenylalanine is restricted in Phenylketonuria (PKU), not MSUD.
D. Tryptophan: Tryptophan metabolism is not impaired in MSUD.
E. Tyrosine: Tyrosine is involved in disorders like PKU and tyrosinemia but is not relevant to MSUD.
Q.13 – A 7-year-old boy presents with confusion, lethargy, and episodes of vomiting. Laboratory tests reveal significantly elevated blood ammonia levels, indicating hyperammonemia. Imaging shows mild cerebral edema. The first line of defense in the brain against hyperammonemia operates through which of the following mechanisms?
A. Asparagine formation
B. Glutamate synthesis
C. Glutamine synthesis
D. Urea formation
E. Ammonia excretion
Correct Answer: C. Glutamine synthesis.
Explanation: In hyperammonemia, the brain detoxifies excess ammonia by converting it to glutamine via the enzyme glutamine synthetase, using glutamate and ammonia as substrates. This mechanism is critical in reducing ammonia toxicity in the brain. However, excessive glutamine accumulation can lead to osmotic imbalances, contributing to cerebral edema and worsening neurological symptoms.
Incorrect Options:
A. Asparagine formation: Asparagine synthesis from aspartate is unrelated to ammonia detoxification.
B. Glutamate synthesis: While glutamate incorporates ammonia, it is a precursor for glutamine synthesis, which is the main detoxification mechanism.
D. Urea formation: Urea synthesis occurs in the liver, not in the brain.
E. Ammonia excretion: The brain does not excrete ammonia; instead, it relies on glutamine synthesis for detoxification.
Q.14 – A 45-year-old man presents with fatigue and muscle weakness. Laboratory tests show elevated levels of alanine and abnormal liver enzyme activity. A deficiency of a coenzyme required for transamination reactions is suspected. Which of the following is required as a coenzyme for transamination reactions?
A. Cobalamin
B. Coenzyme A
C. Folic acid
D. Pyridoxal-P
E. Thiamine pyrophosphate
F. Biotin
Correct Answer: D. Pyridoxal-P
Explanation: Pyridoxal phosphate (Pyridoxal-P or PLP), a derivative of vitamin B6, is the coenzyme required for transamination reactions. These reactions involve the transfer of an amino group from one molecule to another, essential for amino acid metabolism. PLP forms a Schiff base intermediate with amino acids, aiding in the catalytic activity of aminotransferases.
Incorrect Options:
A. Cobalamin: Cobalamin (vitamin B12) is involved in methylation and rearrangement reactions, such as the conversion of homocysteine to methionine, but not in transamination.
B. Coenzyme A: Coenzyme A participates in acyl group transfer reactions, such as the formation of acetyl-CoA, but not in amino group transfer.
C. Folic acid: Folic acid is a coenzyme for one-carbon metabolism, such as in purine and thymidine synthesis, unrelated to transamination.
E. Thiamine pyrophosphate (TPP): TPP is a coenzyme involved in decarboxylation reactions, such as in the pyruvate dehydrogenase complex, but not in transamination.
F. Biotin: Biotin is a coenzyme for carboxylation reactions, such as in pyruvate carboxylase, and does not play a role in transamination.
Q.15 – A 12-year-old patient presents with developmental delay, skeletal abnormalities, and lens dislocation. Laboratory tests confirm elevated levels of homocysteine in the blood, leading to a diagnosis of Homocystinuria. Which of the following vitamins is not recommended for supplementation in this condition?
A. Folic acid
B. Pyridoxal-P
C. Vitamin B12
D. Vitamin C
Correct Answer: D. Vitamin C
Explanation: Vitamin C is not directly involved in the metabolism of homocysteine and is not recommended as part of the treatment for Homocystinuria. Treatment focuses on vitamins that aid in remethylation or transsulfuration pathways.
Incorrect Options:
A. Folic acid: Folic acid is essential for the remethylation of homocysteine to methionine, mediated by methionine synthase.
B. Pyridoxal-P: Pyridoxal phosphate (vitamin B6) is a coenzyme for cystathionine β-synthase, which converts homocysteine to cystathionine in the transsulfuration pathway.
C. Vitamin B12: Vitamin B12 is required for the remethylation of homocysteine to methionine, working alongside folic acid.
Q.16 – Which of the following statements about glutamate dehydrogenase is correct?
A. Required for transamination reactions
B. Universally present in all the cells of the body
C. Can utilize either NAD⁺ or NADP⁺
D. Catalyzes the conversion of glutamate to glutamine
E. Functions exclusively in the cytosol
Correct Answer: C. Can utilize either NAD⁺ or NADP⁺
Explanation: Glutamate dehydrogenase (GDH) is a unique enzyme that can use either NAD⁺ or NADP⁺ as a coenzyme. It catalyzes the oxidative deamination of glutamate to α-ketoglutarate, releasing ammonia. This dual coenzyme specificity enables GDH to function in both catabolic (energy-producing) and anabolic (biosynthetic) pathways.
Incorrect Options:
A. Required for transamination reactions: GDH does not directly participate in transamination, which is catalyzed by aminotransferases using pyridoxal phosphate as a coenzyme.
B. Universally present in all the cells of the body: GDH is predominantly found in the mitochondria of liver and kidney cells, not universally in all cells.
D. Catalyzes the conversion of glutamate to glutamine: This reaction is catalyzed by glutamine synthetase, not glutamate dehydrogenase.
E. Functions exclusively in the cytosol: GDH is localized in the mitochondria, not in the cytosol.
Q.17 – A child was brought to the pediatric OPD with a complaint of the passage of black-colored urine. A disorder of phenylalanine metabolism was diagnosed. A low phenylalanine diet and supplementation with vitamin C were recommended. Which enzyme defect is expected in this child?
A. Fumarylacetoacetate hydrolase
B. Homogentisic acid oxidase
C. Phenylalanine hydroxylase
D. Tyrosine transaminase
E. 4-Hydroxyphenylpyruvate dioxygenase
Correct Answer: B. Homogentisic acid oxidase
Explanation: The black-colored urine is characteristic of alkaptonuria, a disorder caused by a deficiency of homogentisic acid oxidase, which is involved in the degradation of tyrosine in the phenylalanine metabolism pathway. The enzyme defect leads to an accumulation of homogentisic acid, which oxidizes and darkens upon exposure to air, causing the distinctive black urine. Vitamin C supplementation is used to reduce oxidative damage and prevent ochronosis.
Incorrect Options:
A. Fumarylacetoacetate hydrolase: A deficiency in this enzyme causes tyrosinemia type I, leading to liver and kidney failure, not black-colored urine.
C. Phenylalanine hydroxylase: Deficiency in this enzyme results in phenylketonuria (PKU), which is associated with developmental delays and a musty body odor, not black urine.
D. Tyrosine transaminase: Deficiency leads to tyrosinemia type II, characterized by corneal ulcers, hyperkeratosis of the palms and soles, and elevated tyrosine, but not black urine.
E. 4-Hydroxyphenylpyruvate dioxygenase: A defect here leads to tyrosinemia type III, which causes mild intellectual disabilities and ataxia but not black urine.
Q.18 – A 30-year-old male presents with symptoms of depression and tremors. Laboratory evaluation reveals low levels of dopamine in the cerebrospinal fluid. Supplementation with the precursor amino acid is recommended. Dopamine is synthesized from which of the following amino acids?
A. Histidine
B. Methionine
C. Lysine
D. Tryptophan
E. Tyrosine
Correct Answer: E. Tyrosine
Explanation: Dopamine is synthesized from tyrosine through a multi-step enzymatic pathway. Tyrosine is first converted to L-DOPA by tyrosine hydroxylase, and then L-DOPA is converted to dopamine by DOPA decarboxylase. Tyrosine is the direct precursor of dopamine.
Incorrect Options:
A. Histidine: Histidine is a precursor for histamine, not dopamine.
B. Methionine: Methionine is involved in methylation reactions via S-adenosylmethionine (SAM) but not in dopamine synthesis.
C. Lysine: Lysine is primarily involved in protein synthesis and the production of carnitine but not in dopamine synthesis.
D. Tryptophan: Tryptophan is the precursor for serotonin and melatonin, not dopamine.
Q.19 – In mammalian tissue, serine can act as a biosynthetic precursor for which of the following amino acids?
A. Arginine
B. Glycine
C. Lysine
D. Methionine
E. Cysteine
Correct Answer: B. Glycine
Explanation: In mammalian tissues, serine serves as a precursor for glycine through the action of serine hydroxymethyltransferase, which transfers a hydroxymethyl group from serine to tetrahydrofolate (THF), forming glycine and 5,10-methylene-THF.
Incorrect Options:
A. Arginine: Arginine is synthesized from ornithine and citrulline in the urea cycle, not from serine.
C. Lysine: Lysine is an essential amino acid that must be obtained from the diet and cannot be synthesized from serine.
D. Methionine: Methionine is an essential amino acid obtained from the diet, not synthesized from serine.
E. Cysteine: While serine is indirectly involved in cysteine synthesis (via homocysteine in the transsulfuration pathway), it is not a direct precursor.
Q.20 – A 5-year-old child presents with developmental delay, seizures, and a musty body odor. Laboratory tests reveal elevated phenylalanine levels and a deficiency in the enzyme responsible for converting phenylalanine to tyrosine. Hydroxylation of phenylalanine to tyrosine requires all of the following except:
A. Glutathione
B. Molecular oxygen
C. NADPH
D. Tetrahydrobiopterin
Correct Answer: A. Glutathione
Explanation: The hydroxylation of phenylalanine to tyrosine, catalyzed by phenylalanine hydroxylase, requires tetrahydrobiopterin (BH4) as a cofactor, molecular oxygen (O2) as a substrate and NADPH to regenerate BH4. Glutathione, although involved in other enzymatic detoxification and antioxidant processes, is not required for this reaction.
Incorrect Options:
B. Molecular oxygen: Required as a substrate for the hydroxylation reaction.
C. NADPH: Necessary for the regeneration of tetrahydrobiopterin (BH4), which acts as a cofactor for phenylalanine hydroxylase.
D. Tetrahydrobiopterin: BH4 is an essential cofactor for phenylalanine hydroxylase in the conversion of phenylalanine to tyrosine.
