In urea cycle disorder, which of the following substance can be used to reduce the levels of ammonia?
Ans. (B) Phenylbutyrate(Ref: Harper's Illustrated Biochemistry 31st Ed; Page no- 534)Phenylbutyrate diverts urea into an alternate pathway and reduces the amount of ammonia. Hence, acting as ammonia scavenger.Other drugs that can be used to achieve the same outcome (ammonia scavengers) are:#Phenylacetate and benzoate: Excess nitrogen can be removed by giving IV Phenylacetate and Benzoate which respectively binds with glutamine and glycine to produce phenylacetylglutamine and hippuric acid which are excreted in urine.#Arginine: It is an essential amino acid and it provided IV to resume protein synthesis except in arginine deficiency.#IV glucose is the primary treatment in urea cycle disorder along with lipid infusion in comatose patients to avoid catabolism and ammonia production.Extra MileThe Urea Cycle DisordersDefective enzymeMetabolites that accumulate in the blood/urineDisorderArgininosuccinate lyaseAmmonia, Argininosuccinate* Argininosuccinic aciduria* Trichorrhexis nodosa is seen in Argininosuccinic aciduriaArginaseAmmonia, arginine* Hyperargininemia* The clinical symptoms of the condition are quite different from those of urea cycle enzyme defects.* A progressive spastic diplegia with scissoring of the lower extremities, choreoathetotic movements and loss of developmental mile stone in a previously normal infant.Argininosuccinate synthetaseAmmonia, citrulline* Citrullinemia Type-I (Classic citrullinemia).* It is the second most common defect in urea cycle as with an OTC deficiency.* If not treated earlier; it can leads to severe Mental retardation.Carbamoyl phosphate synthetase IAmmonia* Hyperammonemia Type-I* It is one of the fatal disorders, very rarely seen.* No treatment existsOrnithine transcarbamylaseAmmonia, orotic acid* Hyperammonemia Type-II* It is the most common defect in urea cycle as with an OTC deficiency.* It is an X-linked partially dominant inheritance. (All other urea cycle disorders are Autosomal recessive.* Ornithine transcarbamylase defective hence carbamoyl phosphate accumulates in the mitochondria diffusing into the cytoplasm and activating pyrimidine synthesis.
L-carnitine
Phenylbutyrate
Isoleucine
Glutamate
Environment and Health