Error in biochem rapid review?

[snd5014]

Rapid Review Biochemistry has carbamoyl phosphate synthetase deficiency (CPS) listed as the cause of orotic acidemia (pg 126). They say that it would elevate carbamoyl phosphate in the cytosol, pushing the path to elev. orotate.

This really doesn't make sense, how would a deficiency of CPS lead to accumulation of its product? Also it is unclear if they meant CPSI or CPSII (although deficiency of neither would elevate carabmoyl phosphate).

My thought is that a deficiency of CPSI, would lead to findings similar to OTC deficiency with elev. urea.

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[lackli]

I agree with you; seems like a mistake to me. A deficiency in either carbomoyl phosphatase I or II would not result in excess orotic acid.

There two ways to get orotic aciduria:

1. OTC deficiency which would increase levels of carbomoyl phosphate and this excess is converted to orotic acid. There is also hyperammonia in this type of deficiency because the urea cycle is interfered with.

2. Enzyme deficiencies converting orotic acid to UMP. This would be without hyperammonia.

This is directly from pg 68 and 105 of first aid 2011.

 

[bbydoc]

a kaplan biochem video explained this very well and you are right, RR is wrong in this case.

orotic aciduria is one way to differentiate between CPS deficiency and OTC deficiency. literally everything else in clinical presentation as well as blood biochemistry is the same, the only difference is in OTC you have orotic aciduria and it is x-linked recessive as opposed to autosomal recessive (CPS).

 

[snd5014]

Actually another thought real quick.

With Orotic aciduria the deficiency is pyrimidine synthesis, so this would make sense to elevate orotic acid and have megaloblastic anemia (since no pyrimidine synthesis). There is no elevated NH4 because the urea cycle is not affected.

In OTC deficiency carabamoyl phosphate backs up into the pyrimidine pathway and resulting in elevated orotic acid, also have NH4 elevated because can't process carabamoyl phosphate from NH4 backs that up.

If CPSI is defiicient then of course NH4 is elevated, but the carbamoyl phosphate was never made so it shouldn't back up pyrimidine synthesis so orotic acid levels are normal????

Also witht the genetics just want to check: Pyrimidine synthesis enzyme deficiency in orotic aciduria is autosomal recessive, OTC deficiency is X recessive, what is CPSI deficiency?