Question

Which of the following would be the worst enzymatic failure?

Ornithin Transcarbamoylase

   Argininosuccinase

Carbamoyl Phosphate Synthetase I

Answer 1

There are mostly six enzymes that play important role in the break down and removal of nitrogen in the body, a process known as the urea cycle. Three of them are

1. Ornithin Transcarbamoylase (OTC)
2. Argininosuccinate lyase (ASL)
3. Carbamoyl Phosphate Synthetase I (CPS1)

Ornithine transcarbamylase (OTC) deficiency is a rare X-linked genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase (OTC). Absence of OTC activity in males is as severe as CPS1 deficiency. Approximately 15% of carrier females develop hyperammonemia during their lifetime and many require chronic medical management for hyperammonemia. Individuals may be lacking in energy (lethargic) or unwilling to eat, and have a poorly-controlled breathing rate or body temperature. Infants with this disorder may be described as "floppy" and can experience seizures or coma.

Argininosuccinic aciduria is a rare genetic disorder characterized by deficiency or lack of the enzyme argininosuccinate lyase (ASL). It is the second most common Urea Cycle deficiency (UCD). It is present with rapid-onset hyperammonemia in the newborn period. This enzyme defect is past the point in the metabolic pathway at which all the waste nitrogen has been incorporated into the cycle. Some affected individuals develop chronic hepatic enlargement and elevation of transaminases.

Carbamoylphosphate synthetase I deficiency (CPS1 deficiency) is the most severe of the urea cycle disorders. Individuals with complete CPS1 deficiency rapidly develop hyperammonemia in the newborn period. Children who are successfully rescued from crisis are chronically at risk for repeated bouts of hyperammonemia. It catalyzes the ATP-dependent synthesis of carbamoyl phosphate from glutamine or ammonia and bicarbonate

Thus, Carbamoylphosphate synthetase I is considered as the worst enzymatic failure,