Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly.

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Abstract Text:

G Satyanarayana Reddy,Matthew Robinson,Guochun Wang,G Tayhas R Palmore,Lynn Gennaro,Paul Vouros,Pierre De Clercq,Maurits Vandewalle,Wu Young,Shi Ling,Annemieke Verstuyf,Roger Bouillon,

It is now well established that 1alpha,25(OH)2D3 is metabolized in its target tissues through the modifications of both side chain and A-ring. The C-24 oxidation pathway is the side chain modification pathway through which 1alpha,25(OH)2D3 is metabolized into calcitroic acid. The C-3 epimerization pathway is the A-ring modification pathway through which 1alpha,25(OH)2D3 is metabolized into 1alpha,25(OH)2-3-epi-D3. During the past two decades, a great number of vitamin D analogs were synthesized by altering the structure of both side chain and A-ring of 1alpha,25(OH)2D3 with the aim to generate novel vitamin D compounds that inhibit proliferation and induce differentiation of various types of normal and cancer cells without causing significant hypercalcemia. Previously, we used some of these analogs as molecular probes to examine how changes in 1alpha,25(OH)2D3 structure would affect its target tissue metabolism. Recently, several nonsteroidal analogs of 1alpha,25(OH)2D3 with unique biological activity profiles were synthesized. Two of the analogs, SL 117 and WU 515 lack the C-ring of the CD-ring skeleton of 1alpha,25(OH)2D3. SL 117 contains the same side chain as that of 1alpha,25(OH)2D3, while WU 515 contains an altered side chain with a 23-yne modification combined with hexafluorination at C-26 and C-27. Presently, it is unknown how the removal of C-ring from the CD-ring skeleton of 1alpha,25(OH)2D3 would affect its target tissue metabolism. In the present study, we compared the metabolic fate of SL 117 and WU 515 with that of 1alpha,25(OH)2D3 in both the isolated perfused rat kidney, which expresses only the C-24 oxidation pathway and rat osteosarcoma cells (UMR 106), which express both the C-24 oxidation and C-3 epimerization pathways. The results of our present study indicate that SL 117 is metabolized like 1alpha,25(OH)2D3, into polar metabolites via the C-24 oxidation pathway in both rat kidney and UMR 106 cells. As expected, WU 515 with altered side chain structure is not metabolized via the C-24 oxidation pathway. Unlike in rat kidney, both SL 117 and WU 515 are also metabolized into less polar metabolites in UMR 106 cells. These metabolites displayed GC and MS characteristics consistent with A-ring epimerization and were putatively assigned as C-3 epimers of SL 117 and WU 515. In summary, we report that removal of the C-ring from the CD-ring skeleton of 1alpha,25(OH)2D3 does not alter its target tissue metabolism significantly.

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Publishing Authors By Initials

GS Reddy,M Robinson,G Wang,GT Palmore,L Gennaro,P Vouros,P De Clercq,M Vandewalle,W Young,S Ling,A Verstuyf,R Bouillon,

For similar chemical actions and uses: pharmacologic actions: physiological effects of drugs: growth substances: micronutrients: vitamins research abstracts see: chemical actions and uses: pharmacologic actions: physiological effects of drugs: growth substances: micronutrients: vitamins research

PUBMED ID PMID:

MEDLINE DATE:

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Archives of biochemistry and biophysics

VOLUME: 460

Page Numbers: 254-61

Journal Abbreviation:

ISSN: 0003-9861

DAY: 21

MONTH: 11

YEAR: 2006

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372430

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Keywords Mesh Terms:

KEYWORDS: Vitamins

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly. Information

Substance Name: Calcitriol

Registry Number: 32222-06-3

Grant and Affiliation Information for Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly.

AFFILIATION: Epimer LLC, 4 Richmond Square, Suite 500, Providence, RI 02906, USA. Satya_Reddy@Brown.edu

Country: United States

AGENCY: United States NIDDK

GRANT: DK52488

ACRONYM: DK

MEDLINETA: Arch Biochem Biophys

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly Related Publications

• A New Missense Mutation in the CASR Gene in Familial Interstitial Lung Disease with Hypocalciuric Hypercalcemia and Defective Granulocyte Function.
• A school dental program.
• A thyroid thriller: acute transient and symmetric goiter after fine-needle aspiration of a solitary thyroid nodule.
• Assessment of leisure time exercise behavior by self-report: a concurrent validity study.
• Computer assisted percutaneous placement of augmented iliosacral screws: a reasonable alternative to sacroplasty.
• DENTAL PUBLIC HEALTH IN MONTREAL, 1944-1963.
• Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients.
• How effective is nutritional supplementation for the prevention of stress fractures in female military recruits?
• Hypnotic and opioid anesthetic drug interactions on the CNS, focus on response surface modeling.
• Introduction.
• Management of coagulopathy in the patients with multiple injuries: results from an international survey of clinical practice.
• New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion.
• Red blood cell to plasma ratios transfused during massive transfusion are associated with mortality in severe multiply injury: a retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie.
• Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does not alter its target tissue metabolism significantly.
• The coagulopathy of trauma: a review of mechanisms.
• [Conservative treatment of anal cryptitis and fissure as well as anal thrombosis with a streptokinase-streptodornase gel]
• [The value of scores for therapy planning and therapy evaluation in individual intensive care patients--basic principles]