CYP27A1 is a
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
encoding a
cytochrome P450 oxidase
Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherich ...
, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
. It is most prominently involved in the biosynthesis of
bile acids.
Function
CYP27A1 participates in the degradation of
cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils.
Cholesterol is biosynthesis, biosynthesized by all anima ...
to
bile acids in both the classic and acidic pathways.
It is the initiating enzyme in the acidic pathway to bile acids, yielding
oxysterol
An oxysterol is a derivative of cholesterol obtained by Redox, oxidation involving enzymes and / or pro-oxidants. Such compounds play important roles in various biological processes such as cholesterol homeostasis, lipid metabolism (sphingolipids, ...
s by introducing a
hydroxyl group to the carbon at the 27 position in
cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils.
Cholesterol is biosynthesis, biosynthesized by all anima ...
. In the acidic pathway, it produces
27-hydroxycholesterol from cholesterol whereas in the classic or neutral pathway, it produces
3β-hydroxy-5-cholestenoic acid.
While CYP27A1 is present in many different tissues, its function in these tissues is largely uncharacterized. In
macrophages
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
, 27-hydroxycholesterol generated by this enzyme may be helpful against the production of
inflammatory factors associated with
cardiovascular disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
.
Clinical significance
Mutations in CYP27A1 are associated with
cerebrotendineous xanthomatosis, a rare
lipid
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
storage disease.
Inhibitors of CYP27A1 may be effective as
adjuvants in the treatment of
ER-positive
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
due to inhibition of the production of 27-hydroxycholesterol (which has
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
ic actions and stimulates the growth of ER-positive breast cancer cells).
Some marketed drugs that have been identified as CYP27A1 inhibitors include
anastrozole,
fadrozole,
bicalutamide,
dexmedetomidine,
ravuconazole, and
posaconazole.
Interactive pathway map
See also
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Steroidogenic enzyme
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CYP27 family
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Cerebrotendinous Xanthomatosis*
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