Elevated deoxyuridine triphosphate nucleotidohydrolase (dUTPase) activity in the cobalamin-deficient megaloblastic bone marrow cells.
The biochemical basis underlying the pathogenesis of megaloblastic anemia due to vitamin B12 deficiency was examined. Megaloblastic bone marrow cells show a marked imbalance in the deoxynucleoside triphosphate pools. If cellular dUTP concentration is elevated due to metabolic block in a similar way to dCTP, ensuing uracil misincorporation into DNA would result in deranged DNA composition and impaired cell function. Therefore, dUTP-degrading activity was measured in blood cells from various diseases. dUTPase (dUTP nucleotidohydrolase) activity of bone marrow cells was, on average, 4.4 times higher in 8 patients with untreated megaloblastic anemia than that of other normoblastic conditions. Such elevated dUTPase may help lower cellular dUTP levels in megaloblastic anemia. However, it is not clear whether the observed increase of dUTPase in megaloblastic cells is sufficient to suppress uracil misincorporation below the harmful level.
Sugita
Y
Y
Third Department of Internal Medicine, Gunma University School of Medicine, Japan.
Yamauchi
H
H
Omine
M
M
Maekawa
T
T
D000749:Anemia, Megaloblastic / Q000209:etiology*; D001853:Bone Marrow / Q000196:embryology*; D001854:Bone Marrow Cells; D004247:DNA / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D006801:Humans; D011755:Pyrophosphatases / Q000097:blood / Q000378:metabolism*; D014498:Uracil / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000201:enzymology*
D003845:Deoxycytosine Nucleotides; C024107:2'-deoxycytidine 5'-triphosphate; D014498:Uracil; D004247:DNA; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase