Renal inner medullary choline dehydrogenase activity: characterization and modulation.

Abstract

Betaine belongs to the trimethylamine class of osmolytes (osmotically active substances believed to play an important role in cell volume homeostasis) and has recently been identified in the inner medulla of the mammalian kidney. Trimethylamines accumulate in the renal inner medulla during hypertonic stress, and betaine content in the inner medulla has been shown recently to increase during hypernatremia, yet the mechanisms governing the modulation of trimethylamine content and, in particular, of betaine content are not well understood. In this study, we demonstrate the presence of choline dehydrogenase activity in the renal inner medullas of three separate rat strains. Choline dehydrogenase is the enzyme that catalyzes the first of two successive oxidation steps in the biosynthetic conversion of choline to betaine. The presence of choline dehydrogenase activity in the inner medulla suggests that betaine accumulation in the inner medulla may result, at least in part, through in situ synthesis. The Km and Vmax of the reaction in the inner medullas of Long-Evans rats are 4.7 +/- 0.5 mM and 36.9 +/- 5.0 nmol.mg protein-1.min-1, respectively. These values are similar to the characteristics of choline dehydrogenase in mammalian liver. During hypernatremia, when betaine content of the inner medulla has been shown to increase 1.5-fold, choline dehydrogenase activity remains unchanged (or slightly increased), whereas enzyme activity in the cortex increases approximately 50%. Possible mechanisms of inner medullary betaine accumulation are discussed.