Name - Prabhdeep Singh Virdi Roll No - 215 Course - MBA TECH Chemical

Adrenaline (C9H13NO3) is a catecholamine and

belongs to the family of biogenic amines. It forms colourless to white crystalls (mp: 211-212 C). Adrenaline is air and light sensitive and forms dark products during decomposition.
L-adrenaline has some important biological functions.

On the one hand, it belongs, like the chemically related noradrenaline, to the family of adrenal medulla hormones. The hormone has a big influence on the storage and mobilisation of glycogene and fatty acids and the corresponding metabolic pathways

 R=H

Noradrenaline R = CH3 Adrenaline

 L-adrenaline was isolated from adrenal medulla (name

(lat.): adrenes) by two independent groups (Takamine, Aldrich and von Frth) in 1900 and 1901. It was the first hormone which could be crystallized. The structure determination by Jowett and the first total chemical synthesis by Stolz were achieved in 1904. In 1950, Earl Sutherland was able to show that adrenaline and glucagone induce the metabolism of glycogene. This was the beginning of the determination of the molecular mechanism of hormonal effects.

Molecular Weight Melting Point Water Solubility Standard Heat of Formation Molecular Polarizability

183.21 g/mol 215 C <0.01 g/100mL at 18 C -439.17 kJ/mol 18.676 A3

 65 molecular orbitals (36 occupied, 29 unoccupied)

HOMO of adrenaline

LUMO of adrenaline

 The first total chemical synthesis of adrenaline was

performed in 1904 by F. Stolz et al. pyrochatechol and chloro-acetylchloride react in the presence of phosphorchloridoxide to 3,4-dihydroxy- w chloracetophenone (Fries-rearrangement). After the conversion with methylamine, adrenalone will be reduced with sodiumamalgam to adrenaline.
Severall other syntheses also use adrenalone as

starting material.

 1: Phenylalanine-hydroxylase, 2: Tyrosine-hydroxylase, 3: Aromatic amino-acid

decarboxylase,

4: Dopamine- -hydroxylase,

5: Phenylethanolamine- N-methyl-

transferase

 Five enzymes are involved in the pathway of the

biosynthesis of adrenaline. The first enzyme is the iron containing phenylalaninehydroxylase (also called phenylalanine-4monooxygenase). The second enzyme, tyrosine-hydroxylase, contains iron, too, and catalyses the conversion of tyrosine to L-B -(3,4dihydroxyphenyl)- a -alanine (dopa). After decarboxylation of dopa to dopamine (aromatic amino-acid decarboxylase) the copper-containing enzyme dopamine- -hydroxylase converts dopamine to noradrenaline. The final enzyme noradrenaline-N-methyltransferase then methylates noradrenaline to adrenaline. The biosynthesis occurs in the adrenal medulla

Anabolism and Metabolism

L-adrenaline is a hormone and a neurotransmitter. Such substances mostly transfer short-time impulses and therefore have to be activated and inactivated very fast and effectively. Adrenaline is synthesized in the neurones of the adrenal medulla (see Synthesis) and stored in the chromaffin granula. An activating signal, which can be induced through a low blood glucose level, triggers the release of adrenaline into the blood.

Two enzymes are responsible for the fast and effective degradation of adrenaline: the Catecholamine-O-methyltransferase (COMT) and the Monoaminoxidase (MAO).

 Adrenaline has the opposite effect of insuline. It is a first

messenger hormone and will be released when the glucose level in blood is low. Because of the binding to the -adrenergic receptors, it triggers the adenylatcyclase cascade (or cAMP cascade). This activating cascade effects the mobilisation of glycogene (liver) and triacylglycerines (fat tissue) and a generel increase of the metabolic rate. The resulting rise in blood sugar enables the fermentation of glucose in the muscles. Adrenaline furthermore reinforces these effects, because it increases the secretion of glucagon (a hormone with the same effects as adrenaline) and decreases the release of insulin.

 Adrenaline works also as neurotransmitter and has an

effect on the sympathetic nervous system (heart, lungs, blood vessels, bladder, gut and genitalia). This neurotransmitter will be realeased by nervous stimulation in response to physical or mental stress and binds to a special group of transmembrane proteins - the adrenergic receptors. There are two kinds of adrenergic receptors: the - and -receptors. Its effects are: increase in the rate and strength of the heartbeat, dilation of bronchi and pupils, vasoconstriction, sweating and reduced clotting time of the blood. Blood is shunted from the skin and viscera to the skeletal muscles, coronary arteries, liver and brain.

 L-adrenaline has only a short lifetime because of its fast

degradation. The oral intake of adrenaline has no effect. Therefore it has to be administered parenterally. It is used as sympathicomimeticum (drugs, which support the beating of the heart), broncholyticum (drugs, which relax the brochial muscles) and antiasthmaticum (drugs against asthma). It also is used to staunch or prevent bleedings during surgery or in the case of inner organ bleeding. Because adrenaline leads to contraction of blood vessels, it is administered in combination with local anaesthetics. In this combination, anaesthetics have a longer lasting effect and can be administered in smaller doses.

REFERENCES
http://www2.chemie.uni-

erlangen.de/projects/ChemVis/motm/inde x.html http://en.wikipedia.org/wiki/Catecholamin e http://en.wikipedia.org/wiki/Epinephrine http://chemistry.about.com/od/medicalhea lth/ig/Drug-Photo-Gallery/Epinephrine-orAdrenaline.htm