A 12-year-old boy is brought to the emergency department with severe chest pain. He has had intermittent substernal chest pain for the past few months that typically occurs after heavy activity. The boy's activities have been limited due to the chest pain, and he is no longer able to play on the soccer team. The patient does not use tobacco or illicit drugs. His temperature is 36.7 C (98 F), blood pressure is 130/80 mm Hg, pulse is 132/min, respirations are 24/min, and pulse oximetry is 98% on room air. BMI is 17 kg/m². Physical examination shows an anxious-appearing boy with a rapid but regular pulse. No abnormalities are seen. Troponin is elevated, and ECG reveals ST segment elevations in leads II, III, and aVF. After acute stabilization and treatment, further laboratory workup shows an increased serum methionine level. Which of the following amino acids is most likely essential in this patient?

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11ec160b_36a5_32af_9249_9940394494f5_MD0001_00 The amino acid methionine can be metabolized into S-adenosyl-methionine (SAM), which acts as a methyl-donor for many methyltransferase reactions. After the transfer of a methyl group, SAM is converted into S-adenosyl-homocysteine, which is broken down to form adenosine and homocysteine. Subsequently, the conversion of homocysteine to cystathionine requires the enzyme cystathionine synthase, the amino acid serine, and the cofactor vitamin B₆. Cystathionine is then converted to cysteine by the enzyme cystathionase, which also requires vitamin B₆ as a cofactor. Alternatively, the enzyme methionine synthase uses vitamin B₁₂ as a cofactor to revert homocysteine back to methionine. This patient most likely has homocystinuria, a condition that leads to hypercoagulability and thromboembolic occlusion. Because homocysteine is prothrombotic, individuals with complete cystathionine synthase deficiency can develop premature acute coronary syndrome, as seen in this patient (based on his troponin level and ECG findings). Other clinical features include ectopia lentis (ocular lens displacement) and intellectual disability. The most common cause of homocystinuria is a defect in cystathionine synthase. Affected patients cannot form cysteine from homocysteine; therefore, cysteine is essential in their diet. In addition, homocysteine buildup results in hypermethioninemia, as seen in this patient. (Choice A) The enzyme asparagine synthase converts aspartate to asparagine, the amino acid that is essential for rapidly dividing tumor cells that cannot produce it quickly enough on their own. The chemotherapy drug asparaginase decreases asparagine concentration in tumor cells and leads to lysis of these rapidly growing cells. (Choices C, D, and F) Maple syrup urine disease is an amino acid disorder caused by deficiency of branched-chain α-ketoacid dehydrogenase. This deficiency leads to toxic buildup of branched-chain amino acids (leucine, isoleucine, and valine) and their metabolites, resulting in feeding difficulties, seizures, cerebral edema, and a sweet odor of the urine. (Choice E) Phenylalanine hydroxylase catalyzes the hydroxylation of the essential amino acid phenylalanine to form tyrosine. Deficiency of phenylalanine hydroxylase is the most common cause of phenylketonuria, which results in severe intellectual disability if left untreated. Educational objective: Homocystinuria is most commonly caused by a defect in cystathionine synthase, resulting in an inability to form cysteine from homocysteine. Cysteine becomes essential in affected patients, and homocysteine buildup leads to elevated methionine. Homocysteine is prothrombotic, resulting in premature thromboembolic events (eg, atherosclerosis, acute coronary syndrome) in these patients. __________ References: Hypermethioninemias of genetic and non-genetic origin: A review. (http://www.ncbi.nlm.nih.gov/pubmed/21308989) Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. (http://www.ncbi.nlm.nih.gov/pubmed/20814827)

A 12-Year-Old Boy Is Brought to the Emergency Department with Severe