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Vitamin D3-25-hydroxylase: Tissue occurrence and apparent lack of regulation

1973; Elsevier BV; Volume: 155; Issue: 1 Linguagem: Inglês

10.1016/s0003-9861(73)80008-6

1096-0384

Gabriel F. Tucker, Ruth E. Gagnon, Mark R. Haussler,

Muscle metabolism and nutrition

Vitamin D3-25-hydroxylase is the initial enzyme which participates in the pathway of conversion of vitamin D3 to its hormonal form, 1,25-dihydroxy-vitamin D3. This enzyme was discovered by Horsting and DeLuca (Biochem. Biophys. Res. Commun.36, 251–256 (1969)) and has been reported to occur only in liver and to be controlled via feedback inhibition by the product sterol. Our studies, measuring the conversion of vitamin D3 to 25-hydroxy-vitamin D3 by chick tissue homogenates, indicate that significant amounts of enzyme exist in kidney and intestine as well as liver. Since the kidney is the unique site of the 25-hydroxy-vitamin D3-1-hydroxylase enzyme, renal homogenates are capable of complete conversion of vitamin D3 to its 1,25-dihydroxylated form. Further investigation of the vitamin D3-25-hydroxylase of chick liver homogenates demonstrates that it catalyzes 25-hydroxylation at a slow rate and is not strongly inhibited in the presence of excess product. The enzyme also appears to be unaffected by the vitamin D-status of the chick. Complementary experiments showing the strict control of the 25-hydroxy-vitamin D3-1-hydroxylase enzyme by the vitamin D and calcium status of chicks suggest that the regulation of production of the hormonal form of vitamin D resides almost totally at the level of the kidney 25-hydroxy-vitamin D3-1-hydroxylase.