Biomaterial Database

Localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron. 1981

H Kawashima, and S Torikai, and K Kurokawa

Defined nephron segments were microdissected from the kidney of vitamin D-deficient rats, normal rats, and normal rats treated with 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3]. Tubule segments were incubated with 3H]labeled 25-hydroxyvitamin D3 and the rates of production of 3H]labeled 1 alpha, 25-(OH)2D3 and 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] were determined. Nephron segments tested include the glomerulus, proximal convoluted tubules (PCT), proximal straight tubules (PST), medullary and cortical thick ascending limbs of Henle's loop, distal tubules, and collecting tubules. Production of 1 alpha, 25-(OH)2D3 was detected only in PCT of vitamin D-deficient rats (mean +/- SEM, 0.70 +/- 0.05 fmol/mm per hr); the value decreased to 0.11 +/- 0.05 after parathyroidectomy. By contrast, significant 24,25-(OH)2D3 production occurred in PCT of normal rats (0.23 +/- 0.05 fmol/mm per hr). After administration of 1 alpha, 25-(OH)2D3 to normal rats, the rate of production of 24,25-(OH)2D3 in PCT increased to 0.64 +/- 0.06 fmol/mm per hr and also became apparent in PST (1.07 +/- 0.21). The rates of production of 1 alpha, 25-(OH)2D3 and 24,25-(OH)2D3 in these nephron segments were linear with tubule length over a wide range of lengths per incubation and with the incubation time. The results define the localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron: PCT is capable of producing both 1 alpha, 25-(OH)2D3 and 24,25-(OH)2D3 and PST can produce 24,25-(OH)2D3. the use of defined nephron segments may be useful for study of the distribution and regulation of 25-hydroxyvitamin D3 hydroxylases in the kidney.

UI	MeSH Term	Description	Entries
D007678	Kidney Glomerulus	A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.	Glomerulus, Kidney
D008297	Male		Males
D009399	Nephrons	The functional units of the kidney, consisting of the glomerulus and the attached tubule.	Nephron
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D000262	Adenylyl Cyclases	Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP.	Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013250	Steroid Hydroxylases	Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.	Steroid Hydroxylase,Steroid Monooxygenases,Hydroxylase, Steroid,Hydroxylases, Steroid,Monooxygenases, Steroid
D014808	Vitamin D Deficiency	A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)	Deficiency, Vitamin D,Deficiencies, Vitamin D,Vitamin D Deficiencies
D015090	25-Hydroxyvitamin D3 1-alpha-Hydroxylase	A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol).	25-Hydroxycholecalciferol 1-Hydroxylase,CYP27B1,Calcidiol 1-Monooxygenase,Cytochrome P-450 CYP27B1,25-Hydroxycholecalciferol-1-Hydroxylase,25-Hydroxyergocalciferol 1-alpha-Hydroxylase,25-Hydroxyvitamin D 1-alpha-Hydroxylase,25-Hydroxyvitamin D(3) 1 alpha-Hydroxylase,25-Hydroxyvitamin D2 1-hydroxylase,1-alpha-Hydroxylase, 25-Hydroxyergocalciferol,1-alpha-Hydroxylase, 25-Hydroxyvitamin D,1-hydroxylase, 25-Hydroxyvitamin D2,25 Hydroxycholecalciferol 1 Hydroxylase,25 Hydroxyergocalciferol 1 alpha Hydroxylase,25 Hydroxyvitamin D 1 alpha Hydroxylase,25 Hydroxyvitamin D2 1 hydroxylase,25 Hydroxyvitamin D3 1 alpha Hydroxylase,Calcidiol 1 Monooxygenase,Cytochrome P 450 CYP27B1
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus