Active Transport, with Special Reference to the Amino Acids

ACTIVE TRANSPORT, WITH SPECIAL REFERENCE TO THE AMINO ACIDS HALVOR N. CHRISTENSEN, Ph.D.* I. Active and Inactive Transport Accumulation—the apparent concentration of a substance into an anatomic compartment—usually arises from the partial conversion ofthe substance entering the compartment into something else (for example, a bound form), which, however, appears analytically to be an excess ofthe original substance. The term probably should be applied only when we begin with a reasonable expectation that the analytical method will be specific to the free unmodified form, since the mainjustification for calling attention to this behavior is to promote the discovery of an unexpected structural change. Without this restraint, we could designate almost all assimilation as accumulation. In a large number of instances, however, no structural change in the solute has so far been recognized, and the transfer appears to occur against an electrochemical gradient. In diis case the modified form of the substance presumably is converted back to the original structure after passing a barrier. Perhaps the only completely unequivocal instances ofsuch concentrative transfer are those in which the transfer occurs across a barrier of cells, from one extracellular phase to another, in which case the activity of the solute in the two phases can be measured simultaneously, as in gastric or renal secretion of the hydrogen ion or transfer of the sodium ion across short-circuited frog skin. Cells appear to concentrate a number of solutes into their interior, but here it is much more difficult to establish diat concentration has occurred. * Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan. This paper is based upon a presentation before the Fiftieth Anniversary Session, Division of Medical Sciences, Harvard University, May 30, 1958. The studies mentioned here which derive from the author's laboratory have been supported in part by grants to Tufts University and the University of Michigan by the National Cancer Institute, U.S. Public Health Service. 228 Halvor N. Christensen · Active Transport: Amino Acids Perspectives in Biology and Medicine · Winter 1939 Although measurements in broken cells may show an elevated chemical activity of the substance, one can always argue that the molecular architecture has been profoundly altered in breaking the cells. Some of the peculiarities ofradioactive potassium exchange shown by excised muscle (but not by muscle in situ) have been interpreted to support a major restraint ofcellular potassium and other solutes. Biochemists and microbiologists have frequently assumed, without concern for any of these difficulties, that the accumulation they observe is concentrative. Indeed, active transport is occasionally invoked in investigations where only a facilitation ofaccess has been detected. An exogenous substrate may fail to gain access—that is, to mix with its endogenous equivalent—because of either structural differences between the two or the presence ofanatomic barriers. Mandelstam's results (i) emphasize that these two obstacles to access deserve careful differentiation. Neither is necessarily related to active transport. True, barriers to diffusion are always observed wherever active transport can be detected; otherwise back-diffusion would cancel die active transport. Consequently, in the past, cells often were considered impermeable to many ofthe substances we now believe to be actively concentrated by them; for example, delayed transport led to the conclusion that erythrocytes were impermeable to amino acids. Active transport may probably be considered a specialtype of"mediated transport"—that is, the movement of a substance across a boundary as a transiently formed complex. Most cells do not appear to concentrate sugars; nevertheless, evidence has been obtained that sugars passing into cells interact with a membrane constituent, which suggests mediated transport . Is the glucose concentration by the renal tubular cells an elaboration ofa more widespread cellular process ofmediated glucose transport? A. WHAT DO WE MEAN BY A MEMBRANE? Conceivably inulin may penetrate a cell freely to one depdi, raffinose to a second depdi, and sodium ions to a diird. We might then define any one ofthese three limits as a "membrane." A priori, there are no compelling reasons for regarding the cellular locus ofthe discontinuity in potassium distribution, for example, to be the same as the locus ofthe discontinuity in amino acid distribution, but observations ofclose interactions in the transfer of these solutes now support this possibility (2). In...