recommended ring lettering (left) and atom numbering (right) of the steroid skeleton.
Hundreds of distinct steroids are found in plants, animals, and fungi. All steroids are made in cells either from the sterols lanosterol (animals and fungi) or from cycloartenol (plants). Both lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.
Classification
Taxonomical/Functional
Some of the common categories of steroids:
Animal steroids
*Insect steroids
**Ecdysteroids such as ecdysterone
*Vertebrate steroids
**Steroid hormones
***Sex steroids are a subset of sex hormones that produce sex differences or support reproduction. They include androgens, estrogens, and progestagens.
***Corticosteroids include glucocorticoids and mineralocorticoids. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Most medical 'steroid' drugs are corticosteroids.
***Anabolic steroids are a class of steroids that interact with androgen receptors to increase muscle and bone synthesis. There are natural and synthetic anabolic steroids. In popular language, the word "steroids" usually refers to anabolic steroids.
**Cholesterol, which modulates the fluidity of cell membranes and is the principal constituent of the plaques implicated in atherosclerosis.
Plant steroids
*Phytosterols
*Brassinosteroids
Fungus steroids
*Ergosterols
Structural
It is also possible to classify steroids based upon their chemical composition. One example of how
MeSH performs this classification is available at . Examples from this classification include:
{| class="wikitable"
|-
! align="center" | Class
! align="center" | Examples
! align="center" | Number of carbon atoms
|-
| align="center" | Cholestanes
| align="center" | cholesterol
| align="center" | 27
|-
| align="center" | Cholanes
| align="center" | cholic acid
| align="center" | 24
|-
| align="center" | Pregnanes
| align="center" | progesterone
| align="center" | 21
|-
| align="center" | Androstanes
| align="center" | testosterone
| align="center" | 19
|-
| align="center" | Estranes
| align="center" | estradiol
| align="center" | 18
|-
|}
Gonane (or steroid nucleus) is the hypothetic parent (17-carbon tetracyclic) hydrocarbon molecule without any alkyl sidechains.
Metabolism
Steroids include
estrogen,
cortisol,
progesterone, and
testosterone. Estrogen and progesterone are made primarily in the
ovary and in the
placenta during pregnancy, and
testosterone in the
testes. Testosterone is also converted into estrogen to regulate the supply of each, in the bodies of both females and males. Certain
neurons and
glia in the
central nervous system (CNS) express the
enzymes that are required for the local synthesis of
pregnane neurosteroids, either
de novo or from peripherally-derived sources. The rate-limiting step of steroid synthesis is the conversion of
cholesterol to
pregnenolone, which occurs inside the
mitochondrion.
(IPP) and
dimethylallyl pyrophosphate (DMAPP) form
geranyl pyrophosphate (GPP),
squalene and, finally,
lanosterol, the first steroid in the pathways. Some intermediates are omitted for clarity.]]
Steroid metabolism is the complete set of
chemical reactions in organisms that produce, modify, and consume steroids. These
metabolic pathways include:
steroid synthesis – the manufacture of steroids from simpler precursors
steroidogenesis – the interconversion of different types of steroids
steroid degradation.
===Steroid biosynthesis===
Steroid biosynthesis is an anabolic metabolic pathway that produces steroids from simple precursors. This pathway is carried out in different ways in animals than in many other organisms, making the pathway a common target for antibiotics and other anti-infective drugs. In addition, steroid metabolism in humans is the target of cholesterol-lowering drugs such as statins.
It starts in the mevalonate pathway in humans, with Acetyl-CoA as building blocks, which form DMAPP and IPP. In following steps, DMAPP and IPP form lanosterol, the first steroid. Further modification belongs to the succeeding steroidogenesis.
Mevalonate pathway
The
mevalonate pathway or
HMG-CoA reductase pathway starts with and ends with
dimethylallyl pyrophosphate (DMAPP) and
isopentenyl pyrophosphate (IPP).
Regulation and feedback
Several key enzymes can be activated through
DNA transcriptional regulation on activation of
SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low
cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the
LDL receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.
Pharmacology
A number of
drugs target the
mevalonate pathway:
Statins (used for elevated cholesterol levels)
Bisphosphonates (used in treatment of various bone-degenerative diseases)
Plants and bacteria
In plants and bacteria, the
non-mevalonate pathway uses pyruvate and
glyceraldehyde 3-phosphate as substrates., which are a large class of lipids that include the
carotenoids, and form the largest class of plant
natural products.
Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol. Lanosterol can then be converted into other steroids such as cholesterol and ergosterol.
===Steroidogenesis===
Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids. The pathways of steroidogenesis differ between different species, but the pathways of human steroidogenesis are shown in the figure.
Products of steroidogenesis include:
androgens
*testosterone
estrogens and progesterone
corticoids
*cortisol
*aldosterone
Elimination
Steroids are oxidized mainly by
cytochrome P450 oxidase enzymes, such as
CYP3A4. These reactions introduce oxygen into the steroid ring and allows the structure to be broken up by other enzymes, to form
bile acids as final products. These bile acids can then be eliminated through secretion from the
liver in the
bile. The expression of this oxidase gene can be upregulated by the steroid sensor
PXR when there is a high blood concentration of steroids.
See also
Batrachotoxin
List of steroid abbreviations
References
Further reading
External links
Nomenclature of Steroids Home Page at Queen Mary University of London.
Steroidogenesis
Category:Metabolic pathways
*
