WBR0972

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A newborn baby who was normal at birth is noted to be lethargic, hypothermic and feeding poorly at his first days of life. The nurse witnesses an episode of seizure following which blood laboratory tests are ordered. An elevated level of ammonia is detected. Subsequent studies reveals deficiency in N acetylglutamate synthase. N acetylglutamate is recognized as the regulator of the rate-limiting step of the urea cycle, and its absence leads to abnormalities in urea production and elevated ammonia levels. Shown below is a diagram depicting the different steps of the urea cycle occurring in the mitochondria and cytoplasm of hepatocytes. Which of the following reactions is the rate-limiting step of the urea cycle? ]]
Answer A	AnswerA::A
Answer A Explanation	AnswerAExp::A corresponds to the enzyme carbamoyl phosphate synthetase I which is the rate limitng step of the urea cycle and it is activated by N acetylglutamate.
Answer B	AnswerB::B
Answer B Explanation	[[AnswerBExp::B corresponds to ornithine transcarbamoylase which is not involved in the rate limiting step of the urea cycle.]]
Answer C	AnswerC::C
Answer C Explanation	[[AnswerCExp::C corresponds to arginosuccinate synthetase which is not involved in the rate limiting step of the urea cycle.]]
Answer D	AnswerD::D
Answer D Explanation	[[AnswerDExp::D corresponds to arginosuccinase which is not involved in the rate limiting step of the urea cycle.]]
Answer E	AnswerE::E
Answer E Explanation	[[AnswerEExp::E corresponds to arginase which is not involved in the rate limiting step of the urea cycle.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::The urea cycle involves a set of 5 enzymes that help in the conversion of ammonia into urea which is excreted in the urine. A part of the reactions in the urea cycle occurs in the mitochondria whereas the remaining reactions occur in the cytoplasm of the hepatocytes. The mitochondrial enzymes are: carbamoyl phosphate synthetase I and ornitithine transcarbamoylase (OTC). The cytoplasmic enzymes are: arginosuccinate synthetase, arginosuccinase and arginase. The rate limiting step is the conversion of ammonia and carbon dioxide into carbamoyl phosphate. This reaction is catalyzed by the mitochondrial enzyme carbamoyl phosphate synthetase I. This rate limiting step is activated by N acetylglutamate. Deficiency in N acetylglutamate synthetase, as reported in this newborn, leads to a decreased level of the regulator N acetylglutamate and subsequent dysregulation of the urea cycle. Shown below is a diagram depicting the different steps of the urea cycle. Educational objective: The rate limiting step of the urea cycle involves the enzyme carbamoyl phosphate synthetase I that is activated by N acetylglutamate. Reference: First Aid for the USMLE step 1, 2013. Page 97-106. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::urea cycle, WBRKeyword::carbamoyl phosphate synthetase I, WBRKeyword::N acetylglutamate
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::