THE ADENINE NUCLEOTIDE (AdN) TRANSLOCASE (T): A ROLE IN DEVELOPMENTAL CHANGES

Abstract

Although developmental changes occurring during the first days of extrauterine life have been well-characterized in terms of enzymatic activities, little attention has been given to overall cellular energy metabolism. Investigations of energy metabolism in guinea pig liver mitochondria (m) have shown that m from the newborn (N) have membrane pH gradients and membrane electrical potentials similar to those found in adults. During the first 24 hours after birth, State 3 rates of oxygen consumption (OC) increase 3 fold whereas the uncoupled rates of (OC) increase only 30%. The m AdN increases 3 fold with no change in the ATP/ADP ratio. Titrations with carboxyatractyloside (CAT), a stoichiometric inhibitor of the m AdNT show that the N has only 50% of the AdNT activity of the adult. Furthermore, it is possible to evaluate the role of the AdNT on the regulation of respiration using flux control theory (Eur. J. Biochem. 42:97-105). Briefly, the degree of control (control strength) exerted by a particular step in a pathway is defined as the fractional change in pathway flux produced by a fractional change in the activity of the enzyme comprising that step; the sum of all control strengths in a pathway being equal to 1.0. By applying this theory to inhibitor titrations of the AdNT, it has been shown that at any rate of OC the AdNT has greater control strength over respiration in the N than in the adult. At maximal rates of OC the AdNT has a control strength of 0.98 in the N and 0.56 in the adult. Since the AdNT plays a central role in cellular metabolism and the N period is a time of high energy demand, it seems probable that the AdNT plays a critical role in development.