Reddy G S, Tserng K Y
Department of Pediatrics, Boston University School of Medicine, Massachusetts 02118.
Biochemistry. 1989 Feb 21;28(4):1763-9. doi: 10.1021/bi00430a051.
About a decade ago calcitroic acid was isolated as a major side chain cleaved water-soluble metabolite of 1,25-dihydroxyvitamin D3 [Esvelt, R. P., Schnoes, H. K., & Decula, H. F. (1979) Biochemistry 18, 3977]. Presently, calcitroic acid is being considered as the major excretory form of 1,25-dihydroxyvitamin D3. However, the exact site or sites of calcitroic acid production and the possible side chain modified intermediary metabolites that may be formed during the conversion of 1,25-dihydroxyvitamin D3 into calcitroic acid are not fully understood. In the mean time there have been many advances in our understanding of the side-chain metabolism of 1,25-dihydroxyvitamin D3. It is now well established that both the kidney and the intestine metabolize 1,25-dihydroxyvitamin D3 through the C-24 oxidation pathway according to the following steps: 1,25-dihydroxyvitamin D3----1,24,25-trihydroxyvitamin D3----1,25-dihydroxy-24-oxovitamin D3-----1,23,25-trihydroxy-24-oxovitamin D3. Recently, we identified 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 (C-23 alcohol) as a major side chain cleaved lipid-soluble metabolite of 1,25-dihydroxyvitamin D3 and further extended the aforementioned C-24 oxidation pathway in the kidney by demonstrating 1,23,25-trihydroxy-24-oxovitamin D3 as the precursor of C-23 alcohol [Reddy, G. S., Tserng, K. Y., Thomas, B. R., Dayal, R., & Norman, A. W. (1987) Biochemistry 26, 324]. In this present study, we investigated the metabolic fate of 1,25-dihydroxyvitamin D3 (3 X 10(-10) M) in the perfused rat kidney and identified calcitroic acid as the major water-soluble metabolite of 1,25-dihydroxyvitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)
大约十年前，钙三醇酸作为1,25 - 二羟基维生素D3的一种主要的经侧链裂解产生的水溶性代谢产物被分离出来[埃斯韦尔特，R. P.，施诺斯，H. K.，& 德库拉，H. F.（1979年）《生物化学》18卷，3977页]。目前，钙三醇酸被认为是1,25 - 二羟基维生素D3的主要排泄形式。然而，钙三醇酸产生的确切部位以及在1,25 - 二羟基维生素D3转化为钙三醇酸过程中可能形成的经侧链修饰的中间代谢产物尚未完全明确。与此同时，我们对1,25 - 二羟基维生素D3侧链代谢的认识有了许多进展。现已明确，肾脏和肠道均通过C - 24氧化途径代谢1,25 - 二羟基维生素D3，具体步骤如下：1,25 - 二羟基维生素D3→1,24,25 - 三羟基维生素D3→1,25 - 二羟基 - 24 - 氧代维生素D3→1,23,25 - 三羟基 - 24 - 氧代维生素D3。最近，我们鉴定出1,23 - 二羟基 - 24,25,26,27 - 四去甲维生素D3（C - 23醇）是1,25 - 二羟基维生素D3的一种主要的经侧链裂解产生的脂溶性代谢产物，并通过证明1,23,25 - 三羟基 - 24 - 氧代维生素D3是C - 23醇的前体，进一步扩展了上述肾脏中的C - 24氧化途径[雷迪，G. S.，曾，K. Y.，托马斯，B. R.，达亚尔，R.，& 诺曼，A. W.（1987年）《生物化学》26卷，324页]。在本研究中，我们研究了1,25 - 二羟基维生素D3（3×10⁻¹⁰ M）在灌注大鼠肾脏中的代谢归宿，并鉴定出钙三醇酸是1,25 - 二羟基维生素D3的主要水溶性代谢产物。（摘要截取自250词）
