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CYP24A1 enzyme and Vitamin D - many studies

Proper activationmakes sure that Vitamin D does not accumulate in the body
Too much activationLess vitamin D actually gets to cells
Too little activation Vitamin D accumulates to toxic levels ( <1 in 10,000 people)


VitaminDWiki pages with CYP24A1 in title (32 as of Nov 2022)

This list is automatically updated

Items found: 31
Title Modified
CYP24A1 enzyme and Vitamin D - many studies 04 Nov, 2022
Vitamin D non-responders may have one or more poor genes: GC, LIPC, CYP24A1, and PDE3B – Oct 2022 03 Oct, 2022
Increased Phosphorus increases Vitamin D getting to cells (CYP24A1, pigs) - Aug 2022 25 Aug, 2022
Vitamin D resistant genes (CYP24A1, SMRT, SNAIL) behind a paywall – July 2022 20 Jul, 2022
Poor genes (DBP, CYP24A1, CYP2R, etc.) restrict Vitamin D to cells, increasing COVID hospitalization – May 2022 18 May, 2022
Suicide attempts by males 3.7 X more likely if poor Vitamin D gene (CYP24A1) – Oct 2021 08 May, 2022
Vitamin D Metabolite Profiling and genes (CYP24A1, CYP27B1)– Nov 2021 08 Dec, 2021
3X higher risk of oral cancer if CYP27B1 and CYP24A1 genes were different – May 2012 22 Jan, 2021
Hypertension 2X more likely if poor CYP24A1 vitamin D gene (China) – Jan 2020 10 Jan, 2020
Eye vitamin D may not be associated with blood VitD, but is associated with CYP27B1 and CYP24A1 – Nov 2019 18 Nov, 2019
Kidney Stones are related to poor genes – example of CYP24A1 (Vitamin D) – Nov 2019 16 Nov, 2019
Prostate Cancer associated with various genes, including Vitamin D Receptor and CYP24A1 – Nov 2019 15 Nov, 2019
Acute Coronary Syndrome is associated with poor Vitamin D genes (CYP27B1, CYP24A1) – Nov 2019 15 Nov, 2019
Increased risk of weight gain when gene restricts Vitamin D getting to tissues (CYP24A1 in this case) – Nov 2019 07 Nov, 2019
CYP24A1 gene in cancer cells may actually remove vitamin D from the blood – Oct 2012 16 May, 2019
Hepatitis C 1.4X more likely if poor CYP24A1 gene – May 2019 08 May, 2019
Natural pregnancy 4X more likely if sperm had a lot of CYP24A1 – April 2019 10 Apr, 2019
Vitamin D accumulation in 1 in 300 people due to gene (CYP24A1) can cause Calcium problems – June 2018 31 Dec, 2018
CYP24A1 gene mutation is a cause of rare infant vitamin D toxicity – Aug 2011 31 Dec, 2018
Maternal diabetes with poor Vitamin D gene (CYP24A1) increases risk of diabetes in female offspring by 40 percent – Jan 2018 24 Jan, 2018
Vitamin D gene (CYP24A1) changes decrease breast and pancreatic cancers – meta-analysis Nov 2017 20 Dec, 2017
Calcium problems associated with CYP24A1 (a Vitamin D gene) – Oct 2017 08 Nov, 2017
If Lupus in family – 5 times more likely to get Lupus if low vitamin D and poor CYP24A1 – June 2016 07 Jun, 2017
Rare mutation of gene (CYP24A1) results in Vitamin D accumulating in the body – Jan 2017 23 Jan, 2017
Breast Cancer rate reduced 72 percent by vitamin D gene polymorphism CYP24A1 – Nov 2014 30 Mar, 2016
Colon cancer 30 percent more likely if problems with Vitamin D genes CYP24A1 or CYP27B1 – Nov 2015 16 Nov, 2015
Genes such as CYP27B1, CYP24A1 and Vitamin D – JAMA Nov 2012 16 Nov, 2015
Mutations in CYP24A1 gene (vitamin D) associated with kidney problems – Jan 2013 16 Nov, 2015
Activation (methylation) of CYP2R1 and CYP24A1 predict response to dose of vitamin D – Oct 2013 24 Feb, 2015
Breast cancer and Vitamin D receptors, CP27B1, and CYP24A1 – Sept 2010 26 Nov, 2014
CYP24A1 gene, kidney disease, and vitamin D - May 2011 02 Nov, 2012

Cancers may change CYP24A1 gene


CYP24A1 and Vitamin D - 2011

25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D.
Arch Biochem Biophys. 2012 Jul 1;523(1):9-18. doi: 10.1016/j.abb.2011.11.003. Epub 2011 Nov 12.
Jones G1, Prosser DE, Kaufmann M.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6. gj1 at queensu.ca

CYP24A1 is the cytochrome P450 component of the 25-hydroxyvitamin D(3)-24-hydroxylase enzyme that catalyzes the conversion of 25-hydroxyvitamin D(3) (25-OH-D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) into 24-hydroxylated products, which constitute the degradation of the vitamin D molecule. This review focuses on recent data in the CYP24A1 field, including biochemical, physiological and clinical developments. Notable among these are: the first crystal structure for rat CYP24A1; mutagenesis studies which change the regioselectivity of the enzyme; and the finding that natural inactivating mutations of CYP24A1 cause the genetic disease idiopathic infantile hypercalcemia (IIH). The review also discusses the emerging correlation between rising serum phosphate/FGF-23 levels and increased CYP24A1 expression in chronic kidney disease, which in turn underlies accelerated degradation of both serum 25-OH-D(3) and 1,25-(OH)(2)D(3) in this condition. This review concludes by evaluating the potential clinical utility of blocking this enzyme with CYP24A1 inhibitors in various disease states.
Outline
CYP24A1: biochemistry and catalytic properties
CYP24A1: crystal structure, homology modeling and mutagenesis studies
CYP24A1: physiological role
CYP24A1: regulation by 1,25-(OH)2D3, PTH and FGF-23
CYP24A1: pharmacological role
CYP24A1: human polymorphisms and genome-wide linkage studies
CYP24A1: pathological role and implications in disease
CYP24A1 and genetically-linked idiopathic infantile hypercalcemia
CYP24A1 and genetically-linked hypophosphatemia
CYP24A1: involvement in chronic kidney disease
CYP24A1: involvement in pathogenesis and treatment of hyperproliferative disorders
CYP24A1 inhibitors
Publisher wants $25 for the PDF


Rifampin (an anti-TB drug) reactivated the CYP24A1 gene in one person, stopping Hypercalcemia - May 2022

Long-term efficacy and safety of rifampin in the treatment of a patient carrying a CYP24A1 loss-of-function variant
J Clin Endocrinol Metab . 2022 May 15;dgac315. doi: 10.1210/clinem/dgac315 PDF is behind a $39 paywall
Alessandro Brancatella 1, Daniele Cappellani 1, Martin Kaufmann 2, Antonella Semeraro 1, Simona Borsari 1, Chiara Sardella 3, Fulvia Baldinotti 4, Maria Adelaide Caligo 4, Glenville Jones 2, Claudio Marcocci 1 3, Filomena Cetani 3

Background: Pharmacological therapy may be useful in the treatment of moderate to severe hypercalcemia in patients with infantile hypercalcemia-1 (HCINF1) due to pathogenic variants in the cytochrome P450 24 subfamily A member 1 (CYP24A1). Rifampin is an antituberculosis drug that is a potent inducer of cytochrome P450 3 subfamily A member 4 (CYP3A4), involved in an alternative catabolic pathway of vitamin D. The efficacy of rifampin in improving hypercalcemia was previously reported but many questions remain on the long-term efficacy and safety. Aim of the study is to test the long-term efficacy and safety of rifampin in a patient with HCINF1.

Methods: We report clinical, biochemical and imaging features of a 23-year-old man affected by HCINF1 with moderate hypercalcemia (12.9 mg/dL), symptomatic nephrolithiasis, nephrocalcinosis and impaired kidney function (eGFR 60 mL/min/1.73 m2) treated with rifampin for an overall period of 24 months. Kidney, liver and adrenal function were evaluated at every follow-up visit.

Results: In 2 months, rifampin induced a normalization of serum calcium (9.6 mg/dL) associated with an improvement of kidney function (eGFR 92 mL/min/1.73 m2) stable during the treatment. After 15 months, rifampin was temporally withdrawn because of asthenia, unrelated to impairment of adrenal function. After three months, the timing of drug administration was shifted from the morning to the evening, obtaining the remission of asthenia. At the end of follow-up, the nephrolithiasis disappeared and the nephrocalcinosis was stable.

Conclusions: Rifampin could represent an effective choice to induce a stable reduction of calcium levels in patients with HCINF1, with a good safety profile.


CYP24A1 and kidney disease - May 2011

Curr Opin Nephrol Hypertens. 2011 May 22.
PMID: 21610497 full text online


Possibility of blocking CYP24A1 to enable the benefits of vitamin D - July 2012

25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D.


CYP24A1 as a potential target for cancer therapy.- Jan 2014

Anticancer Agents Med Chem. 2014 Jan;14(1):97-108.
Sakaki T, Yasuda K, Kittaka A, Yamamoto K, Chen TC1.

Increasing evidence has accumulated to suggest that vitamin D may reduce the risk of cancer through its biologically active metabolite, 1α,25(OH)2D3, which inhibits proliferation and angiogenesis, induces differentiation and apoptosis, and regulates many other cellular functions. Thus, it is plausible to assume that rapid clearance of 1α,25(OH)2D3 by highly expressed CYP24A1 could interrupt the normal physiology of cells and might be one cause of cancer initiation and progression. In fact, enhancement of CYP24A1 expression has been reported in literature for many cancers. Based on these findings, CYP24A1-specific inhibitors and vitamin D analogs which are resistant to CYP24A1-dependent catabolism might be useful for cancer treatment. CYP24A1-specific inhibitor VID400, which is an azole compound, markedly enhanced and prolonged the antiproliferative activity of 1α,25(OH)2D3 in the human keratinocytes. Likewise, CYP24A1-resistant analogs such as 2α-(3-hydroxypropoxy)-1α,25(OH)2D3 (O2C3) and its C2-epimer ED-71 (Eldecalcitol), and 19nor- 2α-(3-hydroxypropyl)-1α,25(OH)2D3 (MART-10) showed potent biological effects. Our in vivo studies using rats revealed that MART-10 had a low calcemic effect, which is a suitable property as an anticancer drug. Much lower affinity of MART-10 for vitamin D binding protein (DBP) as compared with 1α,25(OH)2D3 may be related to its more potent cellular activities.
Based on these results, we conclude that

  • (1) high affinity for VDR,
  • (2) resistance to CYP24A1-dependent catabolism,
  • (3) low affinity for DBP, and
  • (4) low calcemic effect

may be required for designing potent vitamin D analogs for cancer treatment. PMID: 23869781


Determinants of vitamin D status: focus on genetic variations.- July 2011

PMID: 21654390 full text online


Search PubMed cyp24a1 "vitamin d" 1355 hits Jan 2020

Some interesting titles as of June 2017

  • Genetic Variants in CYP2R1, CYP24A1 and VDR Modify the Efficacy of Vitamin D<sub>3</sub> Supplementation for Increasing Serum 25-Hydroxyvitamin D Levels in a Randomized Controlled Trial. - July 2014
  • Development of novel Vitamin D Receptor-Coactivator Inhibitors.Feb 2014
  • Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults.Feb 2014 full text online
  • Genetic Predictors of Circulating 25-Hydroxyvitamin D and Risk of Colorectal Cancer. Aug 2013
  • Stress and vitamin D: Altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats. April 2013
  • Colonic vitamin D metabolism: Implications for the pathogenesis of inflammatory bowel disease and colorectal cancer. July 2011
  • Vitamin D-Related Genetic Variants, Interactions with Vitamin D Exposure, and Breast Cancer Risk among Caucasian Women in Ontario. July 2011
  • Mutations in CYP24A1 and Idiopathic Infantile Hypercalcemia June 2011 free text here and online
  • Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes. May 2011 full text on-line
  • Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells.- with free paper
  • CYP24A1 Is an Independent Prognostic Marker of Survival in Patients with Lung Adenocarcinoma. Feb 2011
  • Effects of 25-hydroxyvitamin D3 on proliferation and osteoblast differentiation of human marrow stromal cells require CYP27B1/1?-hydroxylase.
  • Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects.
  • Vitamin D pathway gene variants and prostate cancer prognosis.
  • Cytochromes P450 are essential players in the vitamin D signaling system.
  • CYP24A1 inhibition enhances the antitumor activity of calcitriol.
  • Epigenetic regulation of vitamin D 24-hydroxylase/CYP24A1 in human prostate cancer.
  • Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet
  • Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease.
  • Epigenetic regulation of vitamin D converting enzymes.
  • The vitamin D / CYP24A1 story in cancer.
  • Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis.
  • Asthma and genes encoding components of the vitamin D pathway. - free text

CLICK HERE for Clinical Trials of CYP24A1: 25 as of May 2022


Clinical trials of Genes and Vitamin D 228 as of May 2022


Wikipedia: P450 enzyme group (CYP24A1 is a member of the group)

https://en.wikipedia.org/wiki/Cytochrome_P450 June 2017

FamilyFunctionMembersNames
CYP1drug and steroid (especially estrogen) metabolism, benzoapyrene toxification (forming (+)-benzoapyrene-7,8-dihydrodiol-9,10-epoxide)3 subfamilies, 3 genes, 1 pseudogeneCYP1A1, CYP1A2, CYP1B1
CYP2drug and steroid metabolism13 subfamilies, 16 genes, 16 pseudogenesCYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP2R1, CYP2S1, CYP2U1, CYP2W1
CYP3drug and steroid (including testosterone) metabolism1 subfamily, 4 genes, 2 pseudogenesCYP3A4, CYP3A5, CYP3A7, CYP3A43
CYP4arachidonic acid or fatty acid metabolism6 subfamilies, 12 genes, 10 pseudogenesCYP4A11, CYP4A22, CYP4B1, CYP4F2, CYP4F3, CYP4F8, CYP4F11, CYP4F12, CYP4F22, CYP4V2, CYP4X1, CYP4Z1
CYP5thromboxane A2 synthase1 subfamily, 1 geneCYP5A1
CYP7bile acid biosynthesis 7-alpha hydroxylase of steroid nucleus2 subfamilies, 2 genesCYP7A1, CYP7B1
CYP8varied2 subfamilies, 2 genesCYP8A1 (prostacyclin synthase), CYP8B1 (bile acid biosynthesis)
CYP11steroid biosynthesis2 subfamilies, 3 genesCYP11A1, CYP11B1, CYP11B2
CYP17steroid biosynthesis, 17-alpha hydroxylase1 subfamily, 1 geneCYP17A1
CYP19steroid biosynthesis: aromatase synthesizes estrogen1 subfamily, 1 geneCYP19A1
CYP20unknown function1 subfamily, 1 geneCYP20A1
CYP21steroid biosynthesis2 subfamilies, 1 gene, 1 pseudogeneCYP21A2
CYP24vitamin D degradation1 subfamily, 1 geneCYP24A1
CYP26retinoic acid hydroxylase3 subfamilies, 3 genesCYP26A1, CYP26B1, CYP26C1
CYP27varied3 subfamilies, 3 genesCYP27A1 (bile acid biosynthesis), CYP27B1 (vitamin D3 1-alpha hydroxylase, activates vitamin D3), CYP27C1 (unknown function)
CYP397-alpha hydroxylation of 24-hydroxycholesterol1 subfamily, 1 geneCYP39A1
CYP46cholesterol 24-hydroxylase1 subfamily, 1 geneCYP46A1
CYP51cholesterol biosynthesis1 subfamily, 1 gene, 3 pseudogenesCYP51A1 (lanosterol 14-alpha demethylase)

Omega-3 reduces problems due to CYP2E1 – Aug 2017

Omega-3 Polyunsaturated Fatty Acids Normalize the Functions of Mitochondria, Pro- and Antioxidant Enzymes of, and Cytochrome P450 2E1 Expression after Isoproterenol-Induced Myocardial Injury
International Journal of Physiology and Pathophysiology, DOI: 10.1615/IntJPhysPathophys.v8.i2.40 , pages 131-139

We studied the effect of dietary ω-3 polyunsaturated fatty acids (ω-3 PUFA) on the subsarcolemmal and interfibrillar mitochondrial fractions of rat myocardium, changes in expression of cytochrome P450 (CYP2E1), and the activity of pro-antioxidant enzymes after isoproterenol-induced myocardial injury. It has been found that ω-3 PUFA (Epadol 0.1 ml/100 g for 4 weeks) significantly reduces the swelling of the subsarcolemmal and interfibrillar mitochondrial fractions by 65.52% and 54.84%, respectively, indicating a decrease in damage to the mitochondrial function during isoproterenol-induced injury (two daily subcutaneous injections of isoproterenol at the dose of 60 mg/kg). In case of isoproterenol-induced myocardial injury, the use of ω-3 PUFAs prevents a decrease in the activity of antioxidant enzymes, namely catalase and superoxide dismutase (2.65 and 7.1 times, respectively). We have revealed that the development of oxidative stress after isoproterenol-induced myocardial injury can be triggered by a significant increase in the expression of cytochrome P450 2E1 (73.3%), and applying of ω-3 PUFAs prevents such changes.


Chart: Blood test does not notice when a poor CYP24A1 gene stops Vitamin D from getting to cells

Blood Test Misses a lot (VDW 3439)
Click here for more information

CYP24A1 enzyme and Vitamin D - many studies        
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