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Deoxythymidine monophosphate
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Glyceraldehyde-3-phosphate
Methylmalonyl coenzyme-A
Nicotinamide adenine dinucleotide
Succinyl coenzyme-A
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This patient who presents with fatigue and pallor but a normal neurologic exam after restricting her dietary intake most likely has anemia due to folate deficiency. Folate is required for the production of deoxythymidine monophosphate. Dietary folate is converted to tetrahydrofolate, which serves as a coenzyme for methylation reactions. These reactions are important for the synthesis of nitrogenous bases using enzymes such as thymidylate synthase. Patients with folate deficiency will therefore have defective production of deoxythymidine monophosphate and inhibited synthesis of DNA. Clinically, this defect in DNA production is seen most prominently in hematologic precursors as these cells are constantly dividing to regenerate circulating erythrocytes. Abnormal and delayed division due to this DNA formation defect will therefore result in a macrocytic, megaloblastic anemia with hypersegmented neutrophils. Odewole et al. discuss how folate deficiency has been almost eliminated in the American population after mandatory folic acid fortification of most cereal grains. Less than 0.5% of the population still has folate deficiency due to dietary reasons. Incorrect Answers: Answer 2: Glyceraldehyde-3-phosphate production requires the cofactor thiamine. Thiamine deficiency can also be caused by malnutrition; however, it will present with either beriberi (peripheral neuropathy and muscle wasting) or Wernicke/Korsakoff syndrome (ataxia, confusion, ophthalmoplegia, and confabulations). Answer 3: Methylmalonyl coenzyme-A production requires the cofactor biotin. Biotin deficiency can be caused by excessive consumption of raw eggs and presents with dermatitis, alopecia, and gastroenteritis. Answer 4: Nicotinamide adenine dinucleotide production requires the cofactor pyridoxine. Pyridoxine deficiency can be caused by isoniazid and would present with peripheral neuropathy, sideroblastic anemia, and stomatitis. Answer 5: Succinyl coenzyme-A production requires the cofactor cobalamin. Cobalamin deficiency can also present with megaloblastic anemia; however, it will also present with neurologic symptoms such as paresthesias due to subacute combined degeneration of the dorsal columns of the spinal cord. Bullet Summary: Folate deficiency presents with megaloblastic anemia without neurologic findings due to defective production of deoxythymidine monophosphate.
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