NMR STUDIES OF CELLULAR METABOLISM

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This program is aimed at the development and application of in vivo NMR spectroscopic methods for studying metabolism and its perturbation by chemical toxins. The two primary applications during the past year were: (1) measurements or oxygen levels in the vitreous compartment of the rabbit eye, and its perturbation by various agents, and (2) studies of the effects of boric acid on the carbohydrate metabolism of Sertoli cells. In the first series of studies, oxygen levels have been determined based on the concentration-dependent perturbation of the spin lattice relaxation rate of perfluorotributyl amine. This approach requires that either all or a portion of the vitreous humor be replaced by the perfluorocarbon. Two types of measurement were carried out, one in which the vitreous was entirely replaced, and a second in which small, 5 um spheres of perfluorocarbon were placed in the eye. Effects of damage to the blood- retinal barrier on the oxygen level of the vitreous were quantified, and a protective effect of steroids was demonstrated. A second series of studies is aimed at understanding the physiological effects of boric and boronic acids, and the potential basis for the toxic effects of these compounds which have been reported. Although boron is an essential element for plants, no need in animal systems has been established. Recently it has been demonstrated that at relatively high levels boric acid is selectively toxic to the male reproductive system. NMR studies of the effects of boric acid on the metabolism of sertoli cell cultures have been carried out using carbon-13 labeled glucose. An initial series of measurements indicates that the glutamine/glutamate ratio is significantly reduced in cells exposed to boric acid.