Steroide Cholesterol

Sterane skeleton I.Sterane skeleton (sterane or gonane or perhydrocyclopentanophenanthrene) Sterane Sterane R=Q=CH 3, Z=H, long alkyl, etc.

Classification II.Classification a.Sterols (zoosterols as cholesterol, phytosterols and mycosterols b.Steroid vitamines (vitamin D group) c.Sex hormones (estrogens, gestagens as progesterone, androgens as testosterone) d.Corticosteroids (cortisol, aldosteron) e.Cardiac glycosides (strophantin, digitoxin) f.Steroid alkaloids (solanidine, tomatidine)

Zoosterols Cholesterol Occurrence: In the tissues of vertebrates, the main sterol is cholesterol (Greek, chole, bile), abundant in adrenals (10%, w/w), nervous tissues (2%,w/w), liver (0.2%,w/w) and gall stones. Isolation (1770 Poulletier de La Salle) from gall stones; (1815 M.E. Chevreul) from the unsaponifiable fraction of animal fats (cholesterol=Greek, khole, bile and stereos, solid).

Cholesterol I Gallstones containing cholesterol

Cholesterol II a. Numbering b. Stereoisomerism: 2 8 stereoisomers, cholesterol is one of the isomers. c. Relative configuration: C-10-CH 3 group serves as reference point for stereochemical designation. (The ringsystem is approximately planar.)

Cholesterol III Side groups at C-10 and C-13 are above the plane of the rings (  - substituents) indicated with a solid line. Side groups project below the plane of the ringsystem are designated as  -substituents indicated with a dashed line.

Cholesterol IV c. Cis or trans ring fusion (or ring junctions) The two cyclohexane rings can be joined in either cis or trans configuration. They two fused cyclohexane rings can form cis-decalin, both angular groups are on the same side of the ring, trans-decalin, angular groups are on opposite sides of the ring.

Cholesterol V Reduction of cholesterol CholestanolCoprostanol Cholestanol Coprostanol (5  -cholestan-3  -ol)(5  -cholestan-3  -ol) A/B tr, B/C tr, C/D trA/B cis, B/C tr, C/D tr (Cholesterol is partly excreted in the form of sterols cholestanol and coprostanol.)

Cholesterol VI d. Conformaton of steroids conformation of cholestane (planar ringsystem) In cholestane R=Q=CH 3, Z=isooctyl In adrostane R=Q=CH 3, Z=H

Cholesterol V d. Conformaton of steroids conformation of cholic acid Cholic acid (coprostane skeleton)

Cholesterol VI Skeletal hydrocarbons of steroids: Cholestane, coprostane, androstane, pregnane Pregnane

Cholesterol VII 2. Physical properties Solid, its watersolubility at 25  C: 4.7  M/L Plasma level: 3,1-5,7 mM/L in lipoprotein complexes. (In chylomicrons, in VLDL, in LDL and in HDL.) In the lipoproteins about 30 % of it exists as free, about 70 % of it exists as ester. In the bile the cholesterol is esterified only in 4 %. (solubilisation by phospholipids and salt of bile acids)

Cholesterol VIII Solubilization of cholesterol (schematic figure of LDL) Atherosclerotic plaque blocking most of the lumen of the blood vessel.

Biological role of cholesterol Component of membranes Precursor of the major class of steroids

Biosynthesis of cholesterol I

Biosynthesis of cholesterol II

Mycosterols (Ergosterol) Isolation: from yeast Importance: component of fungal membranes Precursor of vitamin D 2 (provitamin)

Vitamin D group (vitamin D 2 and D 3 ) I Deficiency in childhood: rickets (inadequate calcification of cartilage and bone). It was characterized as Children’s disease of the English. Deficiency in adults: osteomalacia (lack of mineralization of bone with normal matrix) Occurrence of vitamin D 3 (cholecalciferol): in fish liver oils. Biosynthesis of vitamin D 3 from 7-dehydrocholesterol

Vitamin D group II Biosynthesis of vitamin D 3

D 2 -Vitamin (ergocalciferol) D 2 -Vitamin D 2 -Vitamin (Formation from ergosterol)

Bile acids I Biosynthesis: from cholesterol in the liver (C 27  C 24 ) Structure: cholanic acid is parent compound of the bile acids. Primary bile acids: cholid acid and chenodeoxycholic acid. Cholic acid

Bile acids II Conjugated bile acids (glycocholic acid and taurocholic acid) Secondary bile acids – mono- and dihydroxi derivatives (lithocholic acid and deoxycholic acid) Physiological role: emulsification of fats (amphoteric character)

Sex hormones

Female sex hormone I Estrogenes Structure: A-ring is aromatic. Estrone Estradiol

Female sex hormone II Production: in ovaries (and in adrenal cortex) from androgens. Physiological role: play pivotal role in female reproduction, in bone metabolism and in the maintenance of cardiovascular system. Estradiol is more potent.

Female sex hormone III (Progesteron) Production: in the ovaries Physiological role: Progesterone prepares the uterus for egg implantation, maintains pregnancy, and prevents further ovulation during pregnancy. Structure: pregnane derivative

Steroid contraceptive agents NorgestrelEthynylestradiol

Male sex hormones I TestosteronAndrosteron

Male sex hormones II Structure: androstane skeleton Production: in the testes (in the adrenal cortex) Physiological role: sexual differencies in nonreproductive system, maturation of sperms, etc. Testosteron is more potent.

Anabolic steroids I Structure: androsteron or testosteron skeleton or 19-norsteroids. 17-MethyltestosteronNorethandrolone Anabolic steroids = Synthetic substances related to male sex hormones. “Anabolic” refers to muscle- building.

Anabolic steroids II Side effects: Abuse of anabolic steroids, however, can lead to serious health problems, some irreversible.

Corticosteroids I Glucocorticoids: cortisol (hydrocortison) Biosynthesis from progesterone, it is a pregnane derivative. Physiological role: synthesis of glycogens, leads to protein breakdown by cells. It ihibits inflammation and allergic resoponses. Cortisol

Mineralcorticoids Biosynthesis: from progesteron Structure: pregnane derivative Physiological role: regulates electrolyte Na +, Cl -, HCO 3 - and fluid balance and the blood pressure. Aldosteron

Steroid anti-inflammatory agents Steroid anti-inflammatory agents: derivatives of cortisol (the effect of the glucocorticoid hormon decreased, but the antiinflammatory and antiallergic increased) MethylprednisoloneDexamethason

Biosynthesis of steroid hormones

Cardiac glycosides I Digitoxin (R=glycosyl group) Digitalis purpurea

Cardiac glycosides II General feature: plant steroids occurring as glycosides in plants. Digitoxin (from Digitalis purpurea, D. lanata), its hydrolysis yields digitoxigenin (aglycon) and a trisaccharide. Structure: ring fusion A/B cis, B/C tr, C/D cis, at 17 an unsaturated lactone ring. Physiological role: heart stimulant

Cardiac glycosides III Strophantin (R=glycosyl group) Strophantus kombe

Cardiac glycosides IV Strophantin (from Strophantus kombe) its hydrolysis yields strophantidine (aglycon) and a trisaccharide. Structure: A/B cis, B/C tr, C/D cis, at C-17 an unsaturated lactone ring, and at C-10 a formyl group Physiological role: heart stimulant

Steroid alkaloids I Structure: they contain steroid aglycons with heterocycylic ring, in the nature they occur as glycosides. Solanidin Solanidin (potatoe, Solanum tuberosum)

Steroid alkaloids II Tomatidin Tomatidin (tomato, Solanum lycopersicum) Importance of steroid alkaloids

Exotic steroids I Shark repellents (pavonines, cholesterol derivatives) Bufotoxines (in Bufo bufo)

Exotic steroids II Ecdysones (20-hydroxyecdysone as the major insect moulting hormone.) Steroid antibiotics (fusidic acid)