The red cells of certain mammals are non-glycolytic due to the change in the phenotypes at birth in which a glucose permeable fetal cell is entirely replaced by a glucose impervious postnatal red cell. The in vivo survival mechanism adopted by this non-glycolytic red cell is not known. Our working hypothesis has been that there exists a metabolically symbiotic relationship between various organs of the body and the red cells. A preliminary result emerging during the previous granting period lends further support to this notion. One of the overall aims of this proposal is to define and characterize this phenomenon in detail. In this characterization process, total hepatectomy, in situ and in vivo perfusion, as well as isolated hepatocytes will be utilized to determine the kinetic properties of ATP depletion upon hepatectomy, to ascertain the metabolic capacity of liver in rejuvenating energy depleted cells and, to identify metabolites formed within and released from the liver and other organs. The physiological significance of this symbiotic interaction will further be ascertained by focussing attention on the transitory postnatal period. In particular, we will examine the extent to which the mechanisms of the facilitated diffusion pathways and the metabolic machinery must undergo alteration so as to adapt to dependence on the organ metabolism. The other objective of this proposal is to isolate and characterize the glucose transport carrier molecules. This will be accomplished using mammalian fetal red cells and reticulocytes which discard their membrane permeability to glucose in the course of aging and maturation process. The loss of membrane permeability may occur by either physically eliminating the transport carrier molecules from the membrane or having the carrier molecules undergo certain conformational changes. Tissue culture conditions for in vitro aging of these cells will be used in order to correlate the development of membrane structures to the glucose permeability.