Acute metabolic acidosis stimulates 3H-25 hydroxyvitamin D production by the rachitic rat liver.

Acute metabolic acidosis alters 1,25 dihydroxyvitamin D metabolism in experimental animals. We have used the NH4Cl-treated rachitic rat as a model to investigate the effect of acidosis on hepatic 25 hydroxyvitamin D (25 OHD) production. NH4Cl ingestion for 4 days was associated with a significant decrease in blood pH (7.44 +/- 0.03 vs 7.17 +/- 0.03, P less than 0.001) and bicarbonate (22.2 +/- 0.9 vs 10.5 +/- 1.6 mEq/liter, P less than 0.001). Acute metabolic acidosis stimulated 3H-25 hydroxyvitamin D production in liver homogenates. Acidosis resulted in a 52% decrease in Km (50.9 nM vs 24.5 nM) and an 11% decrease in the Vmax (554 picomoles/g liver protein/3 h vs 491 picomoles/g liver protein/3 h). The data collectively suggest that an acid load in vivo increases hepatic 25 OHD production and apparently enhances enzyme affinity for substrate.