Role of organic osmolytes in adaptation of renal cells to high osmolality.

Kidney cells accumulate organic osmolytes in order to protect themselves from the high concentrations of NaCl and urea in the blood and interstitial fluid of the renal medulla. The renal medullary organic osmolytes are sorbitol, inositol, betaine and GPC. The concentrations of these solutes in renal medullary NaCl and urea concentration, as summarized in Fig. 8 (the putative controlled steps are highlighted). Sorbitol accumulates by synthesis from glucose, catalyzed by aldose reductase. Hypertonicity increases the transcription of the gene that encodes this enzyme. GPC is synthesized from choline, and the amount retained apparently may be controlled by the activity of GPC diesterase, an enzyme that catabolizes GPC. Inositol and betaine are taken up from the medium by sodium-dependent transport, and this transport is increased by hypertonicity. Control of these processes is slow (hours to days), but a decrease in tonicity causes a transient, rapid efflux of the solutes, which prevents the cells from becoming overly distended. Similar strategies are used by all types of cells, including bacteria and those in plants and animals, that can adapt to hyperosmotic stress.