Question
An infant born to a 25-year-old Caucasian female shows signs of poor feeding and developmental delay. Lab investigations reveal megaloblastic anemia and high levels of homocysteine. Based on laboratory findings, it is suggested that the patient is unable to form methylcobalamin. Synthesis of which of the following substances is most likely impaired in this patient:
| A. |
SAM
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| B. |
Cysteine
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| C. |
Methionine
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| D. |
Cystathionine
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Show Answer
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Correct Answer � C
Explanation
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Ans.C Methionine
Methionine reacts with ATP forming S-adenosylmethionine, “active methionine”. S-adenosyl-methionine is converted to S-adenosyl-homocysteine after transfer of its activated methyl group, and S-adenosyl-homocysteine is then catabolized to form adenosine and homocysteine. Conversion of homocysteine to cystathionine requires the enzyme cystathionine synthase, Vitamin B6 as a cofactor, and the amino acid serine. Alternatively, homocysteine can be converted back to methionine by combining with N-5-methyl-tetrahydrofolate in a reaction requiring vitamin B12 (cobalamin).
In vitamin B12 deficiency, the utilization of the N5-methyl form of tetrahydrofolate in the B12-dependent methylation of homocysteine to methionine is impaired. Because the methylated form cannot be converted directly to other forms of tetrahydrofolate, folate is trapped in the N5-methyl form, which accumulates. The levels of the other forms decrease. Thus, cobalamin deficiency is hypothesized to lead to a deficiency of the tetrahydrofolate forms needed in purine and TMP synthesis, resulting in the symptoms of megaloblastic anemia.
