5-alpha reductase
Encyclopedia
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s involved in steroid metabolism. They participate in 3 metabolic pathways
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
: bile acid
Bile acid
Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...
biosynthesis, androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
and estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
metabolism, and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
.
5α-reductases catalyze
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the following chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
:
- a 3-oxo-5α-steroid + acceptor
a 3-oxo-Delta4-steroid + reduced acceptor
Thus, the two substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
of these enzymes are an 3-oxo-5α-steroid and acceptor, whereas its two products
Product (chemistry)
Product are formed during chemical reactions as reagents are consumed. Products have lower energy than the reagents and are produced during the reaction according to the second law of thermodynamics. The released energy comes from changes in chemical bonds between atoms in reagent molecules and...
are 3-oxo-Delta4-steroid and a reduced acceptor.
Function
5α-reductases convert testosteroneTestosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
, the male sex hormone, into the more potent dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
:
Note the major difference — the Δ4,5 double-bond on the A (leftmost) ring. (The other differences between the diagrams are unrelated to chemical structure.)
These enzymes also participate in the creation of such neurosteroids as allopregnanolone
Allopregnanolone
Allopregnanolone is a prototypic neurosteroid present in the blood and also the brain. It is a metabolite of progesterone and potent modulator of GABAA receptors...
and THDOC
Tetrahydrodeoxycorticosterone
Tetrahydrodeoxycorticosterone , or more preferred allotetrahydroxycorticosterone, is an endogenous neurosteroid. It is synthesized from the adrenal hormone deoxycorticosterone by the action of two enzymes, 5α-reductase type I and 3α-hydroxysteroid dehydrogenase. THDOC has sedative, anxiolytic and...
.
Isoenzymes
There are two isoenzymes, steroid 5α-reductase 1 and 2 (SRD5A1SRD5A1
3-oxo-5-alpha-steroid 4-dehydrogenase 1 is an enzyme that in humans is encoded by the SRD5A1 gene.Steroid 5-alpha-reductase catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone...
and SRD5A2
SRD5A2
3-oxo-5-alpha-steroid 4-dehydrogenase 2 is an enzyme that in humans is encoded by the SRD5A2 gene.Steroid 5-alpha reductase catalyzes the conversion of the male sex hormone testosterone into the more potent androgen, dihydrotestosterone....
).
The second isoenzyme is deficient in 5α-reductase deficiency
5-alpha-reductase deficiency
5-Alpha-reductase deficiency is an autosomal recessive intersex condition caused by a mutation of the 5-alpha reductase type 2 gene.-Normal function:...
, which leads to a form of intersexualism.
Production and inhibition
The enzyme is produced only in numerous tissues in both males and females especially in tissues of the reproductive tract, testis and ovary, namely the skinSkin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, seminal vesicles, prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
and epididymis
Epididymis
The epididymis is part of the male reproductive system and is present in all male amniotes. It is a narrow, tightly-coiled tube connecting the efferent ducts from the rear of each testicle to its vas deferens. A similar, but probably non-homologous, structure is found in cartilaginous...
.
Inhibition of 5α-reductase results in decreased production of DHT, increased levels of testosterone, and, perhaps, increased levels of estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. Gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
is a possible side-effect of 5α-reductase inhibition.
Pharmacology
5α-reductase inhibitor5-alpha-reductase inhibitor
5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...
drugs are used in benign prostatic hyperplasia
Benign prostatic hyperplasia
Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
, prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, male pattern baldness, and hormone replacement therapy
Hormone replacement therapy
Hormone replacement therapy may refer to:*Hormone replacement therapy *Hormone replacement therapy *Hormone replacement therapy *Androgen replacement therapy -See also:...
(male to female) for transgendered women
Trans woman
A trans woman is a male-to-female transsexual or transgender person and the term trans woman is preferred by some individuals over various medical terms. Other non-medical terms include t-girl, tg-girl and ts-girl...
. Both isoforms are also produced in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, where they serve to create the neurosteroid allopregnanolone
Allopregnanolone
Allopregnanolone is a prototypic neurosteroid present in the blood and also the brain. It is a metabolite of progesterone and potent modulator of GABAA receptors...
(5AR type I) and convert T to DHT(5AR type II)(1). Finasteride
Finasteride
Finasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
inhibits the function of only one of the isoenzymes (type 2), whereas dutasteride
Dutasteride
Dutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
inhibits both forms. Saw palmetto extract
Saw palmetto extract
Saw palmetto extract is an extract of the fruit of Serenoa repens. It is rich in fatty acids and phytosterols. It has been used in traditional, eclectic, and alternative medicine for a variety of indications, most notably benign prostatic hyperplasia....
also inhibits both forms.
Nomenclature
This enzyme belongs to the family of oxidoreductaseOxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...
s, to be specific, those acting on the CH-CH group of donor with other acceptors. The systematic name of this enzyme class is 3-oxo-5α-steroid:acceptor Delta4-oxidoreductase. Other names in common use include steroid
- 5α-reductase
- 3-oxosteroid Δ4-dehydrogenase
- 3-oxo-5α-steroid Δ4-dehydrogenase
- steroid Δ4-5α-reductase
- Δ4-3-keto steroid 5α-reductase
- Δ4-3-oxo steroid reductase
- Δ4-3-ketosteroid-5α-oxidoreductase
- Δ4-3-oxosteroid-5α-reductase
- 3-keto-Δ4-steroid-5α-reductase
- 5α-reductase
- testosterone 5α-reductase
- 4-ene-3-ketosteroid-5α-oxidoreductase
- Δ4-5α-dehydrogenase
- 3-oxo-5α-steroid:(acceptor) Δ4-oxidoreductase.
See also
- Cholestenone 5alpha-reductaseCholestenone 5alpha-reductaseIn enzymology, a cholestenone 5alpha-reductase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are 5alpha-cholestan-3-one and NADP+, whereas its 3 products are cholest-4-en-3-one, NADPH, and H+....
- 5α-reductase inhibitors5-alpha-reductase inhibitor5α-Reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...