The renal mitochondrial metabolism of 25-hydroxyvitamin D-3: a possible role for phospholipids

The effect of exogenous phospholipids on chick kidney mitochondrial 25-hydroxyvitamin D-3 metabolism was examined. Phosphatidylserine, phosphatidylcholine and phosphatidylinositol had no effect on either the 1- or 24-hydroxylation of 25-hydroxyvitamin D-3. Phosphatidylethanolamine and cardiolipin both brought about a dose-dependent decrease in the 1-hydroxylase activity in mitochondria from vitamin D-deficient chicks but not from vitamin D-replete chicks. There were no major differences in the phospholipid composition of mitochondria from vitamin D-deficient and -replete chicks nor in the fatty acid composition of these phospholipids. Preliminary kinetic studies suggest that cardiolipin acts as a noncompetitive inhibitor of the 1-hydroxylase in mitochondria isolated from vitamin D-deficient chicks. It does not appear to exert its effect by virtue of altering the distribution of substrate or products. Investigation of the effect of fatty acid methyl esters on the hydroxylase activities suggests that it may be the fatty acid moiety of the phospholipid, rather than the phosphate moiety in the polar head group, that is involved in the phospholipid effect on the hydroxylation of 25-hydroxyvitamin D-3.