Characterisation of 20-hydroxyvitamin D3 metabolism by human liver microsomal cytochromes P450

Chloe Cheng

doi:10.26182/5d1acd143ff30

Characterisation of 20-hydroxyvitamin D3 metabolism by human liver microsomal cytochromes P450

Chloe Cheng

School of Molecular Sciences

Research output: Thesis › Doctoral Thesis

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Abstract

20-Hydroxyvitamin D3 is a derivative of vitamin D3 that exhibits anti proliferative, prodifferentiative and immunomodulatory effects, thus showing promise as a therapeutic drug for the treatment of cancers and inflammatory diseases. To further characterise 20-hydroxyvitamin D3, its metabolism by human liver was investigated and it was found to be metabolised to three products, each with an additional hydroxyl group. The major cytochrome P450 enzyme responsible for these products was CYP3A4, with CYP2R1 playing a lesser role. These metabolic products, present in human serum, displayed stronger inhibition of melanoma cell proliferation than 20-hydroxyvitamin D3. Thus, liver P450s appear to activate 20-hydroxyvitamin D3.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Attwood, Paul, Supervisor Tuckey, Robert, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	17 Jun 2019
DOIs	https://doi.org/10.26182/5d1acd143ff30
Publication status	Unpublished - 2019

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10.26182/5d1acd143ff30

THESIS - DOCTOR OF PHILOSOPHY - CHENG YunnSan Chloe - 2019
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title = "Characterisation of 20-hydroxyvitamin D3 metabolism by human liver microsomal cytochromes P450",

abstract = "20-Hydroxyvitamin D3 is a derivative of vitamin D3 that exhibits anti proliferative, prodifferentiative and immunomodulatory effects, thus showing promise as a therapeutic drug for the treatment of cancers and inflammatory diseases. To further characterise 20-hydroxyvitamin D3, its metabolism by human liver was investigated and it was found to be metabolised to three products, each with an additional hydroxyl group. The major cytochrome P450 enzyme responsible for these products was CYP3A4, with CYP2R1 playing a lesser role. These metabolic products, present in human serum, displayed stronger inhibition of melanoma cell proliferation than 20-hydroxyvitamin D3. Thus, liver P450s appear to activate 20-hydroxyvitamin D3.",

keywords = "Vitamin D, 20-Hydroxyvitamin D3, Cytochrome P450, CYP3A4, Liver metabolism, CYP2R1, Endoplasmic reticulum",

author = "Chloe Cheng",

year = "2019",

doi = "10.26182/5d1acd143ff30",

language = "English",

school = "The University of Western Australia",

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TY - THES

T1 - Characterisation of 20-hydroxyvitamin D3 metabolism by human liver microsomal cytochromes P450

AU - Cheng, Chloe

PY - 2019

Y1 - 2019

N2 - 20-Hydroxyvitamin D3 is a derivative of vitamin D3 that exhibits anti proliferative, prodifferentiative and immunomodulatory effects, thus showing promise as a therapeutic drug for the treatment of cancers and inflammatory diseases. To further characterise 20-hydroxyvitamin D3, its metabolism by human liver was investigated and it was found to be metabolised to three products, each with an additional hydroxyl group. The major cytochrome P450 enzyme responsible for these products was CYP3A4, with CYP2R1 playing a lesser role. These metabolic products, present in human serum, displayed stronger inhibition of melanoma cell proliferation than 20-hydroxyvitamin D3. Thus, liver P450s appear to activate 20-hydroxyvitamin D3.

AB - 20-Hydroxyvitamin D3 is a derivative of vitamin D3 that exhibits anti proliferative, prodifferentiative and immunomodulatory effects, thus showing promise as a therapeutic drug for the treatment of cancers and inflammatory diseases. To further characterise 20-hydroxyvitamin D3, its metabolism by human liver was investigated and it was found to be metabolised to three products, each with an additional hydroxyl group. The major cytochrome P450 enzyme responsible for these products was CYP3A4, with CYP2R1 playing a lesser role. These metabolic products, present in human serum, displayed stronger inhibition of melanoma cell proliferation than 20-hydroxyvitamin D3. Thus, liver P450s appear to activate 20-hydroxyvitamin D3.

KW - Vitamin D

KW - 20-Hydroxyvitamin D3

KW - Cytochrome P450

KW - CYP3A4

KW - Liver metabolism

KW - CYP2R1

KW - Endoplasmic reticulum

U2 - 10.26182/5d1acd143ff30

DO - 10.26182/5d1acd143ff30

M3 - Doctoral Thesis

ER -

Characterisation of 20-hydroxyvitamin D3 metabolism by human liver microsomal cytochromes P450

Abstract

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