HUMAN FETAL XANTHINE OXIDASE

Abstract

Xanthine oxidase (E.C. 1.2.3.2.) has been implicated in the pathogenesis of perinatal postischemic and hyperoxic tissue injuries through its action on the accumulated substrate, hypoxanthine (Hx), and concomitant oxygen free radical production. We measured the activity of xanthine dehydrogenase/oxidase (XOD), and its apparent Km for the main physiological substrate, hypoxanthine, in human fetal liver, intestine, brain, and myocardium. Autopsy samples from 45 fetuses (10-20 gestational weeks), 9 preterm babies (25-28 weeks), and 15 term babies were included in the study. XOD-activity increases in the liver and decreases in the intestine with gestation. During the last trimester the hepatic activity increases almost twofold to a mean of about 0.5 nmol/mg protein/min, while that in the intestine decreases to a third, a mean of about 0.3 nmol/mg protein/min. The apparent Km for Hx is 4.8-5.5 μM in the intestine throughout gestation and in the liver at term, but higher than 30 μM in the liver during the first half of pregnancy. The activity is below 20 pmol/mg protein/min in the brain, and undetectable in the myocardium. Thus, human fetal liver and intestine have substantial enzymatic capacity to convert Hx and/or xanthine to uric acid throughout a gestation. This is a prerequisite but not proof of the involvement of XOD in the pathogenesis of perinatal ischemia-reperfusion injury.