Metabolism of the vitamin D analog EB 1089: identification of in vivo and in vitro liver metabolites and their biological activities

Biochemical Pharmacology
A M KissmeyerG Jones

Abstract

1(S),3(R)-dihydroxy-20(R)-(5'-ethyl-5'-hydroxy-hepta-1'(E),3'(E)-dien -1'-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene (EB 1089) is a novel analog of the vitamin D hormone, calcitriol that has been modified in the side-chain resulting in an increased metabolic stability relative to other side-chain modified analogs (e.g. calcipotriol and 22-oxacalcitriol). To further investigate the metabolism of EB 1089, we set out to study this metabolism both in the rat in vivo as well as in the postmitochondrial liver fractions from rat, man, and minipig in vitro. The same pattern of metabolism was observed in all biological systems employed, both in vivo and in vitro, namely 26- and 26a-hydroxylation of EB 1089. The same metabolites were produced using cultured cell systems (Shankar et al., see this issue). All the possible isomers of 26- and 26a-hydroxy EB 1089 were synthesised and these were compared to biologically generated material using HPLC, NMR, and GC-MS techniques. The predominant natural isomer observed in vitro and in vivo in rats as well as in vitro in humans was identified to be (25S),26R-hydroxy EB 1089. The biological activities of the EB 1089 metabolites on cell growth regulation were 10- to 100-fold lower than that of EB 1...Continue Reading

References

Dec 15, 1992·Biochemical and Biophysical Research Communications·A J BrownE Slatopolsky
May 29, 1992·Biochemical and Biophysical Research Communications·M GrieffA J Brown
Apr 1, 1991·Endocrinology·A S DussoA J Brown
Apr 13, 1989·The New England Journal of Medicine·H ReichelA W Norman
Mar 16, 1981·Biochemical and Biophysical Research Communications·T A ReinhardtR L Horst
Aug 1, 1981·Archives of Biochemistry and Biophysics·Y TanakaH F DeLuca
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·Y D GuoG Jones
Dec 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S RoyH S Tenenhouse
Sep 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·I S MathiasenL Binderup

❮ Previous
Next ❯

Citations

Apr 6, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·John M StrotherRobert Dreicer
Jul 10, 2003·Molecular and Cellular Endocrinology·Veronica A Tovar Sepulveda, Miriam Falzon
May 8, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·A M KissmeyerE Binderup
Feb 13, 2001·Molecular and Cellular Endocrinology·G Pirianov, K W Colston
May 19, 2001·The Journal of Steroid Biochemistry and Molecular Biology·C M HansenL Binderup
Oct 19, 2000·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A M Kissmeyer, J T Mortensen
Jul 1, 2004·The Journal of Steroid Biochemistry and Molecular Biology·John H White
Nov 19, 2013·The Prostate·Declan DohertyPaul Daniel Thompson
Jun 1, 2010·Endocrinology and Metabolism Clinics of North America·Glenville Jones
Jul 11, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Amit Kumar, D Fernando Estrada
Jan 10, 2002·Journal of Andrology·Tara C Polek, Nancy L Weigel
Oct 28, 1998·Physiological Reviews·G JonesH F DeLuca
May 23, 2002·Science·Makoto MakishimaDavid J Mangelsdorf
Feb 23, 2011·Archives of Biochemistry and Biophysics·Steve Y RhieuG Satyanarayana Reddy

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.