Steroid

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This article is about a family of polycyclic hydrocarbons. For the performance-enhancing substance, see Anabolic steroid.

IUPAC-recommended ring-lettering (left) and atom-numbering (right) ofcholestane, a prototypical steroid skeleton.[1] The four rings A-D form the gonanenucleus of the steroid.

Stick model of the steroid lanosterol. The total number of carbons (30) reflects its triterpenoid origin.

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol andtestosterone and the anti-inflammatory drug dexamethasone. The core of steroids is composed of twenty carbon atoms bonded together that take the form of four fused rings: threecyclohexane rings (designated as rings A, B and C in the figure to the right) and one cyclopentane ring (the D ring). The steroids vary by the functional groups attached to this four-ring core

and by the oxidation state of the rings. Sterols are special forms of steroids, with a hydroxyl group at position-3 and a skeleton derived from cholestane.[1] Hundreds of distinct steroids are found in plants, animals and fungi. All steroids are made in cells either from the sterolslanosterol (animals and fungi) or from cycloartenol (plants). Both lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.[2]
Contents
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1 Structure 2 Classification

o o

2.1 Taxonomical/functional 2.2 Structural

3 Biosynthesis

3.1 Mevalonate pathway

o o o o

3.1.1 Pharmacology

3.2 DMAPP to lanosterol 3.3 Steroidogenesis 3.4 Regulation 3.5 Alternative pathways

4 Metabolism 5 See also 6 References 7 External links

Structure[edit]
Steroids are a class of organic compounds with a chemical structure that contains the core of gonane or a skeleton derived therefrom. Usually, methyl groups are present at the carbons C-10 and C-13 an alkyl sidechain at carbon C-17 may also be present.

The basic skeleton of a steroid, with standard stereo orientation. R is a side-chain at C-17.

Cholesterol. This steroid is the precursor to other steroidsin the steroidogenesis.

Gonane is the simplest possible steroid and is composed of seventeen carbon atoms, bonded together to form four fused rings. The three cyclohexane rings (designated as rings A, B, and C in the figure below) form the skeleton of phenanthrene; ring D has a cyclopentane structure. Hence, together they are called cyclopentaphenanthrene.[3]

Numbering of rings and of carbon atoms in gonane, the simplest possible steroid.

The structure of cholestane, one of The more complex structure of cholic acid, a bile acid. the comparatively simpler steroids.

Commonly, steroids have a methyl group at the carbons C-10 and C-13 and an alkyl side chain at carbon C-17. Further, they vary by the configuration of the side chain, the number of additional methyl groups, and the functional groups attached to the rings. For example, sterols have a hydroxyl group attached at position C-3. Some exemplary steroids with their structures:

The anabolic steroid testosterone, the principal male sex hormone.

Progesterone, a steroid hormone involved in Medrogestone, a synthetic drug with the female menstrual cycle, pregnancy and embryogenesis. similar effects as progesterone.

An example of functional groups is the hydroxyl group at C-3 common to sterols.

-Sitosterol, a phytosterol showing the hydroxyl group at C3.

Classification[edit]
Taxonomical/functional[edit]
Some of the common categories of steroids:

Animal

Insect

Ecdysteroids such as ecdysterone that controls moulting

Vertebrate

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 mineralocorticoid s. 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

Phytosterols Brassinosteroids (includes several plant hormones) Steroidal alkaloids found notably in Solanaceae

Fungus

Ergosterols

Structural[edit]
It is also possible to classify steroids based upon their chemical composition. One example of how MeSH performs this classification is available at the Wikipedia MeSH catalog. Examples from this classification include:

Class

Examples Number of carbon atoms

Cholestanes cholesterol

27

Cholanes

cholic acid

24

Pregnanes progesterone

21

Androstanes testosterone

19

Estranes

estradiol

18

Gonane (or steroid nucleus) is the parent (17-carbon tetracyclic) hydrocarbon molecule without any alkyl sidechains.[4]

Biosynthesis[edit]
Steroid biosynthesis is an anabolic metabolic pathway that produces steroids from simple precursors. A unique biosynthetic pathway is followed in animals compared to 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.

Simplified version of latter part of steroid synthesis pathway, where the intermediates isopentenyl pyrophosphate (PP or 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.

In humans and other animals, the biosynthesis of steroids follows the mevalonate pathway that uses acetylCoA as building-blocks to form dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).[5] In subsequent steps, DMAPP and IPP are joined to form geranyl pyrophosphate (GPP), which in turn is used to synthesize the steroid lanosterol. Further modifications of lanosterol into other steroids are classified steroidogenesis transformations.

Mevalonate pathway[edit]
Main article: Mevalonate pathway The mevalonate pathway or HMG-CoA reductase pathway starts with and ends with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).

Mevalonate pathway

Pharmacology[edit]
A number of drugs target the mevalonate pathway:

Statins (used for elevated cholesterol levels) Bisphosphonates (used in treatment of various bone-degenerative diseases)

DMAPP to lanosterol[edit]
Isopentenyl pyrophosphate and dimethylallyl pyrophosphate donate isoprene units, which are assembled and modified to form terpenes and isoprenoids,[6] which are a large class of lipids that include the carotenoids, and form the largest class of plant natural products.[7] Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.[8] Lanosterol can then be converted into other steroids such ascholesterol and ergosterol.[8][9]

Steroidogenesis[edit]
"Steroidogenesis" redirects here. Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids.[10] The pathways of steroidogenesis differ between different species as an example the pathways of human steroidogenesis are shown in this figure below:

The human steroidogenesis, with the major classes of steroid hormones, individual steroids andenzymatic pathways. Note that changes in molecular structure compared to the respective precursor are highlighted with white circles.

The major classes of steroid hormones and some prominent members of the human steroidogenesis are:

Progestogens:

Progesterone

Corticosteroids (Corticoids):

Aldosterone (Mineralocorticoids) Cortisol (Glucocorticoids)

Androgens:

Testosterone

Estrogens:

Locations of human steroidogenesis:

Estrogen

Progestogens serve as precursors to all other human steroids thus all human tissues which produce steroids must first convert cholesterol to pregnenolone. This conversion is the rate-limiting step of steroid synthesis, which occurs inside the mitochondrion of the respective tissue.[11]

Corticosteroids are produced in the adrenal cortex. 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.

In addition, 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.

Regulation[edit]
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 lowcholesterol 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.

Alternative pathways[edit]
In plants and bacteria, the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.[6][12]

Metabolism[edit]
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.[13] These bile acids can then be eliminated through secretion from the liver in the bile.[14] The expression of this oxidase gene can be upregulated by the steroid sensor PXR when there is a high blood concentration of steroids.[15]

See also[edit]
pharmacology portal

Batrachotoxin Corticosteroid List of steroid abbreviations Sex steroid Steroid hormone Steroid hydroxylases Steroid sulfatase Steroidogenic acute regulatory protein

References[edit]
1. ^ Jump up to:
a b

G. P. Moss (1989). "Nomenclature of Steroids

(Recommendations 1989)". Pure & Appl. Chem. 61 (10): 1783 1822. doi:10.1351/pac198961101783. PDF"IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). The nomenclature of steroids. Recommendations 1989". Eur. J. Biochem. 186 (3): 42958. December 1989. doi:10.1111/j.1432-1033.1989.tb15228.x. PMID 2606099. 2. Jump up^ "Lanosterol biosynthesis". Recommendations on Biochemical & Organic Nomenclature, Symbols & Terminology. International Union Of Biochemistry And Molecular Biology. 3. 4. Jump up^ PubChem 130801; 219-08-9cyclopentaphenanthrene Jump up^ Edgren RA, Stanczyk FZ (December 1999). "Nomenclature of the gonane progestins". Contraception 60 (6): 313.doi:10.1016/S00107824(99)00101-8. PMID 10715364. 5. Jump up^ Grochowski L, Xu H, White R (2006). "Methanocaldococcus jannaschii uses a modified mevalonate pathway for biosynthesis of isopentenyl diphosphate". J Bacteriol 188 (9): 3192 8.doi:10.1128/JB.188.9.3192-3198.2006. PMC 1447442.PMID 16621811. 6. ^ Jump up to:
a b

Kuzuyama T, Seto H (2003). "Diversity of the biosynthesis

of the isoprene units". Nat Prod Rep 20 (2): 171 83. doi:10.1039/b109860h. PMID 12735695.

7.

Jump up^ Dubey V, Bhalla R, Luthra R (2003). "An overview of the nonmevalonate pathway for terpenoid biosynthesis in plants". J Biosci 28 (5): 63746.doi:10.1007/BF02703339. PMID 14517367.

8.

^ Jump up to:

a b

Schroepfer G (1981). "Sterol biosynthesis". Annu Rev

Biochem 50: 585 621.doi:10.1146/annurev.bi.50.070181.003101.PMID 7023367. 9. Jump up^ Lees N, Skaggs B, Kirsch D, Bard M (1995). "Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiaea review". Lipids 30 (3): 221 6.doi:10.1007/BF02537824. PMID 7791529. 10. Jump up^ Hanukoglu I (Dec 1992). "Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis.". J Steroid Biochem Mol Biol 43 (8): 779804.doi:10.1016/0960-0760(92)903075. PMID 22217824. 11. Jump up^ Rossier MF (2006). "T channels and steroid biosynthesis: in search of a link with mitochondria". Cell Calcium. 40 (2): 155 64. doi:10.1016/j.ceca.2006.04.020.PMID 16759697. 12. Jump up^ Lichtenthaler H (1999). "The 1-Dideoxy-D-xylulose-5phosphate pathway of isoprenoid biosynthesis in plants". Annu Rev Plant Physiol Plant Mol Biol 50: 47 65.doi:10.1146/annurev.arplant.50.1.47. PMID 15012203. 13. Jump up^ Pikuleva IA (2006). "Cytochrome P450s and cholesterol homeostasis". Pharmacol. Ther. 112 (3): 761 73.doi:10.1016/j.pharmthera.2006.05.014.PMID 16872679. 14. Jump up^ Zollner G, Marschall HU, Wagner M, Trauner M (2006). "Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations". Mol. Pharm. 3 (3): 231 51.doi:10.1021/mp060010s. PMID 16749856. 15. Jump up^ Kliewer S, Goodwin B, Willson T (2002). "The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism". Endocr. Rev. 23 (5): 687702.doi:10.1210/er.2001-0038. PMID 12372848.

External links[edit]

Nomenclature of Steroids Home Page at Queen Mary University of London.

Steroidogenesis
[show]

Cholesterol and steroid metabolic intermediates

[show]

Metabolism (Catabolism, Anabolism)

Categories:

Metabolic pathways Steroids

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