WBR0423

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 3-month-old boy is brought by his mother to the physician's office for hypotonia. The mother was recently told that her son's disease may be caused by an enzyme deficiency. Upon further work-up, the physician explains that the deficient enzyme is normally responsible to convert pyruvate to acetyl CoA, and the patient is required to be on a ketogenic diet. Which of the following cofactors is required for the normal functioning of the enzyme deficient in this patient?]]
Answer A	AnswerA::Vitamin B1
Answer A Explanation	AnswerAExp::Vitamin B1 is a cofactor of pyruvate dehydrogenase.
Answer B	AnswerB::Vitamin C
Answer B Explanation	AnswerBExp::Vitamin C is a cofactor for dopamine beta-hydroxylase.
Answer C	AnswerC::Vitamin B3
Answer C Explanation	AnswerCExp::Vitamin B12 is a cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase.
Answer D	AnswerD::Vitamin K
Answer D Explanation	AnswerDExp::Vitamin K is a cofactor for the carboxylase enzyme that catalyzes carboxylation of glutamic acid residues.
Answer E	AnswerE::Vitamin B6
Answer E Explanation	AnswerEExp::Vitamin B6 is required for the synthesis of cystathionine, heme, GABA, dopamine, niacin, and histamine. It is not a cofactor of pyruvate dehydrogenase.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Pyruvate dehydrogenase deficiency is a congenital disease characterized by the inability to convert pyruvate to acetyl-CoA and build-up of lactic acid. The patterns of inheritance of pyruvate dehydrogenase deficiency are numerous and several genetic mutations have been implicated. Typically, pyruvate dehydrogenase deficiency manifests with neurological symptoms (cortical atrophy and delayed development and motor skills) that first appear shortly following birth. Patients with pyruvate dehydrogenase deficiency are required to be on ketogenic diets rich in lysine and leucine, both of which are considered ketogenic amino acids. Pyruvate dehydrogenase contains 3 enzymes that require 5 cofactors for proper functioning: Vitamins B1, B2, B3, B5, and lipoic acid. Educational Objective: Pyruvate dehydrogenase deficiency is characterized by the inability to convert pyruvate to acetyl-CoA. Pyruvate dehydrogenase normally contains 3 enzymes that require 5 cofactors for proper functioning: Vitamins B1, B2, B3, B5, and lipoic acid. References: First Aid 2014 page 92]]
Approved	Approved::Yes
Keyword	WBRKeyword::Pyruvate dehydrogenase, WBRKeyword::Vitamin, WBRKeyword::Enzyme, WBRKeyword::Deficiency, WBRKeyword::Cofactors, WBRKeyword::Acetyl-CoA, WBRKeyword::Pyruvate, WBRKeyword::Hypotonia, WBRKeyword::Pyruvate dehydrogenase deficiency
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::