NEET-PG 2019 - Biochemistry Practice Questions

Q: Glutamine is increased in CSF, blood & urine WITHOUT elevated orotic acid in which defect:

CPS-I. ***CPS-I*** - A deficiency in **Carbamoyl Phosphate Synthetase I (CPS-I)** leads to a severe block in the **urea cycle**, resulting in profound hyperammonemia. - The elevated ammonia is then shunted to produce more **glutamine** (via glutamine synthetase), which serves as a detoxification mechanism but also causes high levels of glutamine in CSF, blood, and urine. *Arginase* - **Arginase deficiency** primarily leads to elevated **arginine** levels and mild to moderate hyperammonemia, but not typically a dramatic increase in glutamine due to the block occurring later in the cycle. - Clinical features include progressive spasticity, growth retardation, and intellectual disability. *Argininosuccinate lyase deficiency* - This deficiency causes accumulation of **argininosuccinate** in body fluids, which is a diagnostic marker, rather than primarily increased glutamine. - It presents with severe hyperammonemia, neurological symptoms, and often hepatomegaly. *Arginosuccinate synthetase* - A deficiency in **argininosuccinate synthetase** (also known as citrullinemia type I) leads to a buildup of **citrulline** and severe hyperammonemia. - While hyperammonemia can indirectly increase glutamine, the primary diagnostic marker is elevated citrulline, and the glutamine increase is not as pronounced or directly symptomatic as in CPS-I deficiency. *OTC* - **Ornithine Transcarbamylase (OTC) deficiency** is the most common urea cycle disorder and leads to severe hyperammonemia, accompanied by elevated **orotic acid** due to carbamoyl phosphate shunting to pyrimidine synthesis. - While hyperammonemia drives glutamine synthesis, the presence of elevated orotic acid is a key differentiator from CPS-I deficiency, which does not have increased orotic acid.

Q: Ammonia causes depletion of which of the following in TCA cycle?

Alpha-ketoglutarate. ***Alpha-ketoglutarate*** - Ammonia is detoxified in the brain by conversion to **glutamine**, a process that consumes **alpha-ketoglutarate** in the glutamate dehydrogenase reaction (alpha-ketoglutarate + NH3 + NADH glutamate + NAD+). - The depletion of **alpha-ketoglutarate** in the TCA cycle impairs cellular respiration and ATP production, contributing to the neurological dysfunction seen in hyperammonemia. *Malate* - While malate is a component of the TCA cycle, its depletion is not a direct consequence of ammonia detoxification. - Ammonia metabolism primarily impacts the availability of alpha-ketoglutarate through the synthesis of glutamate and glutamine. *Oxaloacetate* - Although **oxaloacetate** is a key intermediate in the TCA cycle, its levels are not directly depleted by ammonia metabolism. - **Oxaloacetate** can be replenished through anaplerotic reactions, even if the TCA cycle is slightly inhibited due to alpha-ketoglutarate depletion. *Fumarate* - **Fumarate** is an intermediate of the TCA cycle and is not directly consumed or depleted by the ammonia detoxification pathway. - Its levels would only indirectly be affected if the overall flux of the TCA cycle is significantly reduced due to depletion of other intermediates.

Q: Defect in Menkes disease:

ATP7A (Copper-transporting ATPase). ***ATP7A (Copper-transporting ATPase)*** - **Menkes disease** is an X-linked recessive disorder characterized by a defect in the **ATP7A gene**, which encodes a copper-transporting ATPase. - This defect leads to impaired intestinal absorption and cellular transport of copper, resulting in **copper deficiency** in various tissues despite adequate dietary intake. *Prolyl oxidase* - **Prolyl oxidase** is involved in proline metabolism, and defects are not associated with Menkes disease. - Deficiency of this enzyme is usually linked to hyperprolinemia. *Prolyl hydroxylase* - **Prolyl hydroxylase** is an enzyme critical for the hydroxylation of proline residues in collagen, a step essential for collagen stability. - While collagen synthesis requires copper (for lysyl oxidase), a direct defect in prolyl hydroxylase is not the cause of Menkes disease. *Lysyl oxidase* - **Lysyl oxidase** is a copper-dependent enzyme required for the cross-linking of collagen and elastin, contributing to connective tissue strength. - Although lysyl oxidase activity is reduced in Menkes disease due to copper deficiency, the primary defect is in the **ATP7A transporter**, not the lysyl oxidase enzyme itself.

Question 1

Glutamine is increased in CSF, blood & urine WITHOUT elevated orotic acid in which defect:

Accepted Answer

CPS-I

Answer

Arginase

Answer

Argininosuccinate lyase deficiency

Answer

Arginosuccinate synthetase

Answer

OTC

Question 2

Ammonia causes depletion of which of the following in TCA cycle?

Accepted Answer

Alpha-ketoglutarate

Answer

Malate

Answer

Oxaloacetate

Answer

Fumarate

Question 3

Defect in Menkes disease:

Accepted Answer

ATP7A (Copper-transporting ATPase)

Answer

Prolyl oxidase

Answer

Prolyl hydroxylase

Answer

Lysyl oxidase

NEET-PG 2019 — Biochemistry