A Metabolic Inhomogeneity of Glycine in Viwo

Amino acids are known to be compartmented within the cell, as in glutamine synthesis in rat brain (1, 2) and in protein synthesis in Can&&z utilis (3) and rat diaphragm and lymph node preparations (4). Such compartmentations are often detected by the observation that the specific activity of a synthesis product is greater than that of its apparent precursor for some length of time. Experiments are described in the preceding paper (5) in which a synthetic product (hippurate) had a higher specific activity than its precursor (glycine-C14) for short periods of time (several minutes) in viuo. Here the existence of a glycine compartmentation is questionable; the specific activity effect is transient, and no anatomical or cytological structure coincides with a possible compartment from which the active glycine for hippurate might originate. The time course of the phenomenon seems to depend on the size of the animal in the same way as metabolism (smaller animals are faster), and appreciable changes result from such mild procedures as anesthesia. The location of an active glycine compartment cannot be simply determined from the location of the mitochondria, which are the site of hippurate synthesis (6, 7); liver mitochondria are scattered uniformly throughout the cell, and no one intracellular volume will enclose them all without including almost everything else. Nor can Zilversmit’s rule (8), the handiest method of establishing a precursor compartment, be applied in this case (5). Mitochondria synthesize hippurate of approximately the same specific activity as external glycine, but contain glycine of lower specific activity (9). The amount of this intramitochondrial glycine is too small for it to constitute an inactive glycine compartment capable of accounting for the observed results. Mathematical models of this situation can account for these results semiquantitatively without requiring the assumption of a specific glycine compartment. Information regarding the regulatory mechanisms of the cell may be obtained from such models.