A steroid is a biologically active
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
with four rings arranged in a specific
molecular configuration. Steroids have two principal biological functions: as important components of
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
s that alter
membrane fluidity; and as
signaling molecules
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellular ...
. Hundreds of steroids are found in
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae excl ...
s,
animal
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage ...
s and
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
. All steroids are manufactured in cells from the
sterols
Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the gon ...
lanosterol (
opisthokonts) or
cycloartenol
Cycloartenol is an important triterpenoid of the sterol class which is found in plants. It is the starting point for the synthesis of almost all plant steroids, making them chemically distinct from the steroids of fungi and animals, which are, ...
(plants). Lanosterol and cycloartenol are derived from the
cyclization of the
triterpene squalene.
The steroid
core structure is typically composed of seventeen
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...
atoms, bonded in four "
fused" rings: three six-member
cyclohexane rings (rings A, B and C in the first illustration) and one five-member
cyclopentane
Cyclopentane (also called C pentane) is a highly flammable alicyclic hydrocarbon with chemical formula C5H10 and CAS number 287-92-3, consisting of a ring of five carbon atoms each bonded with two hydrogen atoms above and below the plane. It occ ...
ring (the D ring). Steroids vary by the
functional groups attached to this four-ring core and by the
oxidation state
In chemistry, the oxidation state, or oxidation number, is the hypothetical charge of an atom if all of its bonds to different atoms were fully ionic. It describes the degree of oxidation (loss of electrons) of an atom in a chemical compound. C ...
of the rings.
Sterols are forms of steroids with a
hydroxy group at position three and a skeleton derived from
cholestane
Cholestane is a saturated tetracyclic triterpene. This 27-carbon biomarker is produced by diagenesis of cholesterol and is one of the most abundant biomarkers in the rock record. Presence of cholestane, its derivatives and related chemical compo ...
.
[ ''Also available with the same authors at'' ; ''Also available online at'' ] Steroids can also be more radically modified, such as by changes to the ring structure, for example,
cutting one of the rings. Cutting Ring B produces
secosteroid
A secosteroid () is a type of steroid with a "broken" ring. The word ''secosteroid ''derives from the Latin verb ''secare'' meaning "to cut", and 'steroid'. Secosteroids are alternatively described as a subclass of steroids; ; or derived from st ...
s one of which is
vitamin D3.
Examples include
anabolic steroids
Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...
, the
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
, the sex hormones
estradiol and
testosterone,
and the
anti-inflammatory drug
dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
.
Nomenclature
Gonane
Gonane is a chemical compound with formula , whose molecule can be described as three molecules or entities of cyclohexane and one of cyclopentane, fused in a particular way. More specifically, the molecule can be described as that of cycloh ...
, also known as steran or cyclopentanoperhydrophenanthrene, the simplest steroid and the nucleus of all steroids and sterols,
is composed of seventeen
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...
atoms in carbon-carbon bonds forming four
fused rings in a
three-dimensional shape. The three
cyclohexane rings (A, B, and C in the first illustration) form the skeleton of a
perhydro derivative of
phenanthrene. The D ring has a
cyclopentane
Cyclopentane (also called C pentane) is a highly flammable alicyclic hydrocarbon with chemical formula C5H10 and CAS number 287-92-3, consisting of a ring of five carbon atoms each bonded with two hydrogen atoms above and below the plane. It occ ...
structure. When the two methyl groups and eight carbon
side chains (at C-17, as shown for cholesterol) are present, the steroid is said to have a cholestane framework. The two common 5α and 5β stereoisomeric forms of steroids exist because of differences in the side of the largely planar ring system where the hydrogen (H) atom at carbon-5 is attached, which results in a change in steroid A-ring conformation. Isomerisation at the C-21 side chain produces a parallel series of compounds, referred to as isosteroids.
Examples of steroid structures are:
File:Testosteron.svg, alt=Chemical diagram, Testosterone, the principal male sex hormone
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
and an anabolic steroid
File:Cholsäure.svg, alt=Chemical diagram, Cholic acid, a bile acid, showing the carboxylic acid and additional hydroxyl groups often present
File:Dexamethasone structure.svg, alt=Chemical diagram, Dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
, a synthetic corticosteroid drug
File:Lanosterin.svg, alt=Chemical diagram, Lanosterol, the biosynthetic precursor to animal steroids. The number of carbons (30) indicates its triterpenoid
Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squal ...
classification.
File:Progesteron.svg, alt=Chemical diagram, Progesterone, a steroid hormone involved in the female menstrual cycle, pregnancy, and embryogenesis
File:Medrogestone.png, alt=Chemical diagram, Medrogestone, a synthetic drug with effects similar to progesterone
File:Sitosterol structure.svg, alt=Chemical diagram, β-Sitosterol, a plant or phytosterol
Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phyt ...
, with a fully branched hydrocarbon side chain at C-17 and an hydroxyl group at C-3
In addition to the ring scissions (cleavages),
expansions and
contractions (cleavage and reclosing to a larger or smaller rings)—all variations in the carbon-carbon bond framework—steroids can also vary:
* in the
bond orders within the rings,
* in the number of methyl groups attached to the ring (and, when present, on the prominent side chain at C17),
* in the functional groups attached to the rings and side chain, and
* in the
configuration of groups attached to the rings and chain.
For instance,
sterols such as cholesterol and lanosterol have a
hydroxyl group attached at position C-3, while
testosterone and
progesterone have a carbonyl (oxo substituent) at C-3; of these,
lanosterol alone has two methyl groups at C-4 and cholesterol (with a C-5 to C-6 double bond) differs from testosterone and progesterone (which have a C-4 to C-5 double bond).
Species distribution and function
In
eukaryotes, steroids are found in fungi, animals, and plants.
Fungal steroids
Fungal steroids include the
ergosterols, which are involved in maintaining the integrity of the fungal cellular membrane. Various
antifungal drugs, such as
amphotericin B
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis ...
and
azole antifungals
Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring.
Their names originate from the Hantzsch–Widman nomenclatur ...
, utilize this information to kill
pathogenic fungi.
Fungi can alter their ergosterol content (e.g. through loss of function mutations in the enzymes
ERG3 or
ERG6, inducing depletion of ergosterol, or mutations that decrease the ergosterol content) to develop resistance to drugs that target ergosterol.
Ergosterol is analogous to the
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
found in the cellular membranes of animals (including humans), or the
phytosterols found in the cellular membranes of plants.
All mushrooms contain large quantities of ergosterol, in the range of tens to hundreds of milligrams per 100 grams of dry weight.
Oxygen is necessary for the synthesis of
ergosterol in fungi.
Ergosterol is responsible for the
vitamin D
Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
content found in mushrooms; ergosterol is chemically converted into provitamin D2 by exposure to
ultraviolet light
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiatio ...
.
Provitamin D2 spontaneously forms vitamin D2.
However, not all fungi utilize ergosterol in their cellular membranes; for example, the pathogenic fungal species ''
Pneumocystis jirovecii
''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. P ...
'' does not, which has important clinical implications (given the mechanism of action of many antifungal drugs). Using the fungus ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'' as an example, other major steroids include
ergosta‐5,7,22,24(28)‐tetraen‐3β‐ol,
zymosterol
Zymosterol is an intermediate in cholesterol biosynthesis. Disregarding some intermediate compounds (e.g. 4-4-dimethylzymosterol) lanosterol can be considered a precursor of zymosterol in the cholesterol synthesis pathway. The conversion of zymo ...
, and
lanosterol. ''S. cerevisiae'' utilizes
5,6‐dihydroergosterol in place of ergosterol in its cell membrane.
Animal steroids
Animal steroids include compounds of
vertebrate and
insect
Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pa ...
origin, the latter including
ecdysteroids such as
ecdysterone (controlling molting in some species). Vertebrate examples include the
steroid hormones and cholesterol; the latter is a structural component of
cell membranes that helps determine the fluidity of
cell membranes and is a principal constituent of
plaque (implicated in
atherosclerosis). Steroid hormones include:
*
Sex hormone
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
s, which influence
sex differences
Sexual dimorphism is the condition where the sexes of the same animal and/or plant species exhibit different morphological characteristics, particularly characteristics not directly involved in reproduction. The condition occurs in most anim ...
and support
reproduction. These include
androgens,
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s, and
progestogens.
*
Corticosteroids, including most synthetic steroid drugs, with
natural product classes the
glucocorticoids (which regulate many aspects of
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
and
immune function) and the
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
s (which help maintain blood volume and control
renal excretion of
electrolytes)
*
Anabolic steroids,
natural
Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans ar ...
and synthetic, which interact with androgen receptors to increase muscle and bone synthesis. In popular use, the term "steroids" often refers to anabolic steroids.
Plant steroids
Plant steroids include steroidal
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of simila ...
s found in
Solanaceae and
Melanthiaceae (specially the genus
Veratrum),
cardiac glycosides,
the
phytosterol
Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phyt ...
s and the
brassinosteroids (which include several plant hormones).
Prokaryotes
In
prokaryotes, biosynthetic pathways exist for the tetracyclic steroid framework (e.g. in
mycobacteria)
– where its origin from
eukaryotes is conjectured
– and the more-common pentacyclic
triterpinoid hopanoid framework.
Types
By function
The major classes of
steroid hormones, with prominent members and examples of related functions, are:
*
Corticosteroids:
**
Glucocorticoids:
***
Cortisol, a
glucocorticoid whose functions include
immunosuppression
**
Mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
s:
***
Aldosterone, a
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
that helps regulate
blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure ...
through water and electrolyte balance
*
Sex steroids:
**
Progestogens:
***
Progesterone, which regulates cyclical changes in the
endometrium of the
uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
and maintains a
pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ...
**
Androgens:
***
Testosterone, which contributes to the development and maintenance of male
secondary sex characteristics
**
Estrogens:
***
Estradiol, which contributes to the development and maintenance of female secondary sex characteristics
Additional classes of steroids include:
*
Neurosteroids such as and
allopregnanolone
*
Bile acids such as
taurocholic acid
*
Aminosteroid neuromuscular blocking agents (mainly synthetic) such as
pancuronium bromide
*
Steroidal antiandrogens (mainly synthetic) such as
cyproterone acetate
*
Steroidogenesis inhibitors (mainly exogenous) such as
alfatradiol
* Membrane sterols such as
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
,
ergosterol, and various
phytosterol
Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phyt ...
s
* Toxins such as steroidal
saponins and
cardenolides/
cardiac glycosides
As well as the following class of
secosteroid
A secosteroid () is a type of steroid with a "broken" ring. The word ''secosteroid ''derives from the Latin verb ''secare'' meaning "to cut", and 'steroid'. Secosteroids are alternatively described as a subclass of steroids; ; or derived from st ...
s (open-ring steroids):
*
Vitamin D
Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
forms such as
ergocalciferol,
cholecalciferol, and
calcitriol
By structure
Intact ring system
Steroids can be classified based on their chemical composition. One example of how
MeSH performs this classification is available at the Wikipedia MeSH catalog. Examples of this classification include:
In biology, it is common to name the above steroid classes by the number of carbon atoms present when referring to hormones: C
18-steroids for the estranes (mostly estrogens), C
19-steroids for the androstanes (mostly androgens), and C
21-steroids for the pregnanes (mostly corticosteroids). The classification "
17-ketosteroid" is also important in medicine.
The gonane (steroid nucleus) is the parent 17-carbon tetracyclic hydrocarbon molecule with no
alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...
sidechains.
Cleaved, contracted, and expanded rings
Secosteroids (Latin ''seco'', "to cut") are a subclass of steroidal compounds resulting,
biosynthetically or conceptually, from scission (cleavage) of parent steroid rings (generally one of the four). Major secosteroid subclasses are defined by the steroid carbon atoms where this scission has taken place. For instance, the prototypical secosteroid
cholecalciferol,
vitamin D3 (shown), is in the 9,10-secosteroid subclass and derives from the cleavage of carbon atoms C-9 and C-10 of the steroid B-ring; 5,6-secosteroids and 13,14-steroids are similar.
Norsteroids (
nor-, L. ''norma''; "normal" in chemistry, indicating carbon removal)
and homosteroids (homo-, Greek ''homos''; "same", indicating carbon addition) are structural subclasses of steroids formed from biosynthetic steps. The former involves enzymic
ring expansion-contraction reactions, and the latter is accomplished (
biomimetically) or (more frequently) through
ring closure
A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where a ...
s of
acyclic precursors with more (or fewer) ring atoms than the parent steroid framework.
Combinations of these ring alterations are known in nature. For instance,
ewes who graze on
corn lily ingest
cyclopamine (shown) and
veratramine, two of a sub-family of steroids where the C- and D-rings are contracted and expanded respectively via a
biosynthetic migration of the original C-13 atom. Ingestion of these C-nor-D-homosteroids results in birth defects in lambs:
cyclopia from
cyclopamine and leg deformity from veratramine.
A further C-nor-D-homosteroid (nakiterpiosin) is excreted by
Okinawa
is a Prefectures of Japan, prefecture of Japan. Okinawa Prefecture is the southernmost and westernmost prefecture of Japan, has a population of 1,457,162 (as of 2 February 2020) and a geographic area of 2,281 Square kilometre, km2 (880 sq mi).
...
n
cyanobacteriosponges. e.g., ''
Terpios
''Terpios'' is a genus of sea sponges belonging to the family Suberitidae.
Species
*'' Terpios aploos'' de Laubenfels, 1954
*'' Terpios australiensis'' Hentschel, 1909
*'' Terpios belindae'' Rützler & Smith, 1993
*'' Terpios cruciata'' (Dendy, ...
hoshinota'', leading to coral mortality from black coral disease. Nakiterpiosin-type steroids are active against the signaling pathway involving the
smoothened and
hedgehog proteins, a pathway which is hyperactive in a number of cancers.
Biological significance
Steroids and their metabolites often function as
signalling molecules (the most notable examples are steroid hormones), and steroids and
phospholipids are components of
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
s. Steroids such as cholesterol decrease
membrane fluidity.
Similar to
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
s, steroids are highly concentrated energy stores. However, they are not typically sources of energy; in mammals, they are normally metabolized and excreted.
Steroids play critical roles in a number of disorders, including malignancies like
prostate cancer, where steroid production inside and outside the tumour promotes cancer cell aggressiveness.
Biosynthesis and metabolism
The hundreds of steroids found in animals, fungi, and
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae excl ...
s are made from
lanosterol (in animals and fungi; see examples above) or
cycloartenol
Cycloartenol is an important triterpenoid of the sterol class which is found in plants. It is the starting point for the synthesis of almost all plant steroids, making them chemically distinct from the steroids of fungi and animals, which are, ...
(in other eukaryotes). Both lanosterol and cycloartenol derive from
cyclization of the
triterpenoid
Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squal ...
squalene.
Lanosterol and cycloartenol are sometimes called protosterols because they serve as the starting compounds for all other steroids.
Steroid biosynthesis is an
anabolic
Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breakin ...
pathway which produces steroids from simple precursors. A unique biosynthetic pathway is followed in animals (compared to many other
organism
In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells ( cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fu ...
s), making the pathway a common target for
antibiotics and other anti-infection drugs. Steroid metabolism in humans is also the target of cholesterol-lowering drugs, such as
statins. In humans and other animals the biosynthesis of steroids follows the mevalonate pathway, which uses
acetyl-CoA as building blocks for
dimethylallyl diphosphate (DMAPP) and
isopentenyl diphosphate (IPP).
In subsequent steps DMAPP and IPP conjugate to form
farnesyl diphosphate (FPP), which further conjugates with each other to form the linear triterpenoid squalene. Squalene biosynthesis is catalyzed by
squalene synthase
Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step react ...
, which belongs to the
squalene/phytoene synthase family
The squalene/phytoene synthase family represents proteins that catalyze the head-to-head condensation of C15 and C20 prenyl units (i.e. farnesyl diphosphate and genranylgeranyl diphosphate). This enzymatic step constitutes part of steroid and caro ...
. Subsequent
epoxidation and cyclization of squalene generate lanosterol, which is the starting point for additional modifications into other steroids (steroidogenesis). In other eukaryotes, the cyclization product of epoxidized squalene (oxidosqualene) is cycloartenol.
Mevalonate pathway
The mevalonate pathway (also called HMG-CoA reductase pathway) begins with
acetyl-CoA and ends with
dimethylallyl diphosphate (DMAPP) and
isopentenyl diphosphate (IPP).
DMAPP and IPP donate
isoprene units, which are assembled and modified to form
terpene
Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ...
s and
isoprenoids
The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes" ...
(a large class of lipids, which include the
carotenoids and form the largest class of plant
natural products. Here, the isoprene units are joined to make
squalene and folded into a set of rings to make
lanosterol.
Lanosterol can then be converted into other steroids, such as cholesterol and
ergosterol.
[
Two classes of drugs target the mevalonate pathway: statins (like ]rosuvastatin
Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, ...
), which are used to reduce elevated cholesterol levels, and bisphosphonates (like zoledronate), which are used to treat a number of bone-degenerative diseases.
Steroidogenesis
Steroidogenesis is the biological process by which steroids are generated from cholesterol and changed into other steroids. The pathways of steroidogenesis differ among species. The major classes of steroid hormones, as noted above (with their prominent members and functions), are the progestogens, corticosteroids (corticoids), androgens, and estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s. Human steroidogenesis of these classes occurs in a number of locations:
*Progestogens are the precursors of all other human steroids, and all human tissues which produce steroids must first convert cholesterol to pregnenolone
Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineralocor ...
. This conversion is the rate-limiting step of steroid synthesis, which occurs inside the mitochondrion of the respective tissue.
*Cortisol, corticosterone, aldosterone, and testosterone are produced in the adrenal cortex.
*Estradiol, estrone and progesterone are made primarily in the ovary, estriol in placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
during pregnancy, and testosterone primarily in the testes (some testosterone is also produced in the adrenal cortex).
*Estradiol is converted from testosterone directly (in males), or via the primary pathway DHEA - androstenedione - estrone and secondarily via testosterone (in females).
* Stromal cells have been shown to produce steroids in response to signaling produced by androgen-starved prostate cancer cells.
*Some neurons and glia in the central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
(CNS) express the enzymes required for the local synthesis of pregnenolone, progesterone, DHEA and DHEAS, ''de novo'' or from peripheral sources.
Alternative pathways
In plants and bacteria, the non-mevalonate pathway (MEP pathway) uses pyruvate and glyceraldehyde 3-phosphate as substrates to produce IPP and DMAPP.[
During diseases pathways otherwise not significant in healthy humans can become utilized. For example, in one form of ]congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex ...
a deficiency in the 21-hydroxylase enzymatic pathway leads to an excess of 17α-Hydroxyprogesterone (17-OHP) – this pathological excess of 17-OHP in turn may be converted to dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...
(DHT, a potent androgen) through among others 17,20 Lyase (a member of the cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
family of enzymes), 5α-Reductase and 3α-Hydroxysteroid dehydrogenase.
Catabolism and excretion
Steroids are primarily oxidized by cytochrome P450 oxidase enzymes, such as CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...
. These reactions introduce oxygen into the steroid ring, allowing the cholesterol to be broken up by other enzymes into bile acids. These acids can then be eliminated by secretion from the liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
in bile. The expression of the oxidase gene can be upregulated by the steroid sensor PXR when there is a high blood concentration of steroids. Steroid hormones, lacking the side chain of cholesterol and bile acids, are typically hydroxylated at various ring positions or oxidized at the 17 position, conjugated with sulfate or glucuronic acid and excreted in the urine.
Isolation, structure determination, and methods of analysis
Steroid ''isolation'', depending on context, is the isolation of chemical matter required for chemical structure
A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...
elucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more or the isolation of "analytical quantities" of the substance of interest (where the focus is on identifying and quantifying the substance (for example, in biological tissue or fluid). The amount isolated depends on the analytical method, but is generally less than one microgram.
The methods of isolation to achieve the two scales of product are distinct, but include extraction Extraction may refer to:
Science and technology
Biology and medicine
* Comedo extraction, a method of acne treatment
* Dental extraction, the surgical removal of a tooth from the mouth
Computing and information science
* Data extraction, the pr ...
, precipitation, adsorption
Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...
, chromatography, and crystallization. In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such as LC-MS, are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample.
''Structure determination'' refers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have included NMR and small-molecule crystallography. ''Methods of analysis'' overlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity.
Chemical synthesis
Microbial catabolism of phytosterol
Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phyt ...
side chains yields C-19 steroids, C-22 steroids, and 17-ketosteroids (i.e. precursor
Precursor or Precursors may refer to:
* Precursor (religion), a forerunner, predecessor
** The Precursor, John the Baptist
Science and technology
* Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...
s to adrenocortical hormone In humans and other animals, the adrenocortical hormones are hormones produced by the adrenal cortex, the outer region of the adrenal gland. These polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to str ...
s and contraceptive
Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
s). The addition and modification of functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
s is key when producing the wide variety of medications available within this chemical classification. These modifications are performed using conventional organic synthesis and/or biotransformation techniques.
Precursors
Semisynthesis
The semisynthesis
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
of steroids often begins from precursors such as cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
, phytosterol
Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phyt ...
s, or sapogenin
Sapogenins are the aglycones, or non-saccharide, portions of the family of natural products known as saponins. Sapogenins contain steroid or other triterpene frameworks as their key organic feature. For example, steroidal sapogenins such as tigge ...
s. The efforts of Syntex, a company involved in the Mexican barbasco trade, used '' Dioscorea mexicana'' to produce the sapogenin diosgenin in the early days of the synthetic steroid pharmaceutical industry.
Total synthesis
Some steroidal hormones are economically obtained only by total synthesis from petrochemical
Petrochemicals (sometimes abbreviated as petchems) are the chemical products obtained from petroleum by refining. Some chemical compounds made from petroleum are also obtained from other fossil fuels, such as coal or natural gas, or renewabl ...
s (e.g. 13-alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...
steroids). For example, the pharmaceutical Norgestrel begins from methoxy-1-tetralone
1-Tetralone is a bicyclic aromatic hydrocarbon and a ketone. In terms of its structure, it can also be regarded as benzo-fused cyclohexanone. It is a colorless oil with a faint odor. It is used as starting material for agricultural and pharmace ...
, a petrochemical derived from phenol
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it r ...
.
Research awards
A number of Nobel Prize
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
s have been awarded for steroid research, including:
* 1927 (Chemistry
Chemistry is the scientific study of the properties and behavior of matter. It is a natural science that covers the elements that make up matter to the compounds made of atoms, molecules and ions: their composition, structure, proper ...
) Heinrich Otto Wieland
Heinrich Otto Wieland (; 4 June 1877 – 5 August 1957) was a German chemist. He won the 1927 Nobel Prize in Chemistry for his research into the bile acids.
Career
In 1901 Wieland received his doctorate at the University of Munich while studyin ...
— Constitution of bile acids and sterols and their connection to vitamins
* 1928 (Chemistry) Adolf Otto Reinhold Windaus
Adolf Otto Reinhold Windaus (; 25 December 1876 – 9 June 1959) was a German chemist who won a Nobel Prize in Chemistry in 1928 for his work on sterols and their relation to vitamins. He was the doctoral advisor of Adolf Butenandt who also won ...
— Constitution of sterols and their connection to vitamins
* 1939 (Chemistry) Adolf Butenandt and Leopold Ružička — Isolation and structural studies of steroid sex hormones, and related studies on higher terpene
Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ...
s
* 1950 ( Physiology or Medicine) Edward Calvin Kendall, Tadeus Reichstein, and Philip Hench — Structure and biological effects of adrenal hormones
* 1965 (Chemistry) Robert Burns Woodward — In part, for the synthesis of cholesterol, cortisone, and lanosterol
* 1969 (Chemistry) Derek Barton and Odd Hassel
Odd Hassel (17 May 1897 – 11 May 1981) was a Norwegian physical chemist and Nobel Laureate.
Biography
Hassel was born in Kristiania (now Oslo), Norway. His parents were Ernst Hassel (1848–1905), a gynaecologist, and Mathilde Klaveness ( ...
— Development of the concept of conformation in chemistry, emphasizing the steroid nucleus
* 1975 (Chemistry) Vladimir Prelog — In part, for developing methods to determine the stereochemical course of cholesterol biosynthesis from mevalonic acid via squalene
See also
* Adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex ...
* Batrachotoxin
Batrachotoxin (BTX) is an extremely potent cardio- and neurotoxic steroidal alkaloid found in certain species of beetles, birds, and frogs. The name is from the Greek word grc, βάτραχος, bátrachos, frog, label=none. Structurally-relate ...
* List of steroid abbreviations
The steroid hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hor ...
* List of steroids
List of steroids may refer to:
* List of androgens/anabolic steroids – steroidal androgens/anabolic steroids
* List of androgens/anabolic steroids (alternate) – steroidal androgens/anabolic steroids
* List of steroidal antiandrogens – ste ...
* Membrane steroid receptor
* Pheromone
* Reverse cholesterol transport
Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream.
Cholesterol from non-hepatic peripheral t ...
* Steroidogenesis inhibitor
* Steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It i ...
* Steroidogenic enzyme
References
Bibliography
*
*
* A concise history of the study of steroids.
* A review of the history of steroid synthesis, especially biomimetic.
* Adrenal steroidogenesis pathway.
*
*
{{Authority control
Metabolic pathways
Wikipedia articles with sections published in WikiJournal of Medicine