Transport of β-Hydroxy-β-Methyl-Glutarate and β-Hydroxbutyrate by Renal Brushborder Membrane Vesicles

Summary: The uptake of β-hydroxy-β-methyl-glutarate (HMG) and β-hydroxy-butyrate (β-HB) by renal brushborder membrane vesicles prepared from normal and starved rats was examined. HMG and β-HB uptake show a Na+ gradient-induced overshoot, suggesting luminal cotransport of these organic acids. Kinetic analysis of HMG and β-HB uptake revealed a single component carrier system and a diffusional component for each compound. Vesicles from starved rats exhibit the same transport characteristics as those from normal rats. The transport interactions of other organic acids with HMG were examined and revealed that citrate is a competitive inhibitor, which implies that the compounds share a common organic acid carrier. Speculation: The possibility exists that by administration of high oral doses of citrate, urinary citrate can be elevated sufficiently to competitively inhibit the tubular reabsorption of β-hydroxy-β-methyl-glutarate. This, in addition to the buffering properties of citrate, could be of significance in the treatment of the severe metabolic acidosis seen in patients with β-hydroxy-β-methyl-glutarate-CoA lyase deficiency.