TY - JOUR
T1 - Vitamin D3-25-hydroxylase
T2 - Tissue occurrence and apparent lack of regulation
AU - Tucker, Gabriel
AU - Gagnon, Ruth E.
AU - Haussler, Mark R.
N1 - Funding Information:
Recent investigations in a number of laboratories have lead to the concept that vitamin D3 ~ is metabolized to more polar forms prior to mediating the transport of calcium in intestine and bone (1-4). The initial metabolite in the sequence is 25- 1 Supported in part by United States Public Health Service Grant AlbI15781-01. 2To whom all correspondence should be addressed. 3 Vitamin D~ (cholecalciferol) is defined as a sterol by the International Union of Pure and Applied Chemistry Commission on Nomenclature of Biological Chemistry (J. Amer. Chem. Soc, 82, 5755 (1960)); its chemical name is 9,10-secocholest a-5,7,10 (19)-trien-3t\]-ol. The accepted trivial name "vitamin D~" is utilized in the present report. One International Unit (IU) of vitamin D~ is equivalent to 0.025 ug or 65 pmoles. In the present context, 1 IU of 25-hydroxy-vitamin D3 or 1,25-dihydroxy-vitamin D3 is also defined as being equivalent to 65 pmoles of sterol.
PY - 1973/3
Y1 - 1973/3
N2 - 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.
AB - 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.
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U2 - 10.1016/S0003-9861(73)80008-6
DO - 10.1016/S0003-9861(73)80008-6
M3 - Article
C2 - 4351347
AN - SCOPUS:0015591727
SN - 0003-9861
VL - 155
SP - 47
EP - 57
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -