Which of the following is affected in Megaloblastic anemia?
Ref: Harrison's Principles of Internal Medicine, 18edExplanation:"The common feature of all megaloblastic anemias is a defect in DNA synthesis that affects rapidly dividing cells in the hone marrow" Ref: HarrisonCauses of Megaloblastic Anemia* Vitamin B12. Cobalamin deficiency or abnormalities of cobalamin metabolismFolate deficiency or abnormalities of folate metabolismTherapy with antifolate drugs (e.g., methotrexate)Independent of either cobalamin or folate deficiency and refractory to cobalamin and folate therapy:Acute myeloid leukemiaMyelodysplasiaTherapy with drugs interfering with synthesis of DNA Orotic aciduria (responds to uridine) Thiamine-responsive Megaloblastic anemiaBiochemical Basis of Megaloblastic AnemiaFolates (as the intracellular polyglutamate derivatives) aet as coenzymes in the transfer of single-carbon units.Two of these reactions are involved in purine synthesis and one in pyrimidine synthesis necessary for DNA and RNA replication.Folate is also a coenzyme for methionine synthesis, in which methylcohalamin is also involved and in which THE is regenerated. THF is the acceptor of single carbon units newly entering the active pool via conversion of serine to glycine. Methionine, the other produet of the methionine synthase reaction, is the precursor for S-adenosylmethionine (SAM), the universal methyl donor involved in >100 methyltransferase reactionsThe common feature of all megaloblastic anemias is a defect in DNA synthesis that affects rapidly dividing cells in the bone marrowAll conditions that give rise to megaloblastic changes have in common a disparity in the rate of synthesis or availability of the four immediate precursors of DNAIn deficiencies of either folate or cobalamin. there is failure to convert deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), the precursor of dTTPThis is the ease because folate is needed as the coenzyme 5,10-methylene-THE polyglutamate for conversion of dUMP to dTMP: the availability of 5,10-methylene-THF is reduced in either cobalamin or folate deficiency.
DNA
RNA
Giobin
Iron absorption
Anemia and RBC Disorders