Epinephrine structure

Common Name Dipivalyl epinephrine Structural Formula ... 

As an example, we can compare the structures of epinephrine (adrenaline) and amphetamine. Epinephrine is a natural stimulant that is released in the body in times of stress. Amphetamine (sold under the trade name Benzedrine) is an artificial stimulant that causes many of the same effects as epinephrine. The three -OH groups and the N-H bond in the epinephrine structure cause a greater percentage of that molecule to be polar, so we predict that epinephrine would be more soluble in water than amphetamine (Figure 15.5). 

The three -OH groups and the N-H bond in the epinephrine structure give it a greater percentage of its structure that is polar, so we predict that... 

FIGURE 4.5 The structures of some ammo acids that are not normally found in proteins but that perform other important biological functions. Epinephrine, histamine, and serotonin, although not amino acids, are derived from and closely related to amino acids. 

Catecholamines are biogenic amines with a catechol (o-dihydroxy-benzol) structure. They are synthesized in nerve endings from tyrosine and include dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine). 

The vesicular monoamine transporters (VMATs) were identified in a screen for genes that confer resistance to the parkinsonian neurotoxin MPP+ [2]. The resistance apparently results from sequestration of the toxin inside vesicles, away from its primary site of action in mitochondria. In addition to recognizing MPP+, the transporter s mediate the uptake of dopamine, ser otonin, epinephrine, and norepinephrine by neurons and endocrine cells. Structurally, the VMATs show no relationship to plasma membrane monoamine transporters. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

FIG. 17 Chemical structures of (a) epinephrine hydrochloride, (b) dopamine hydrochloride, (c) isoproterenol hydrochloride, (d) phenylephrine hydrochloride, (e) tolazoline hydrochloride, (f) oxyprenolol hydrochloride, (g) alprenolol hydrochloride, and (h) propranolol hydrochloride. 

In addition to their well known role in protein structure, amino acids also act as precursors to a number of other important biological molecules. For example, the synthesis of haem (see also Section 5.3.1), which occurs in, among other tissues, the liver begins with glycine and succinyl-CoA. The amino acid tyrosine which maybe produced in the liver from metabolism of phenylalanine is the precursor of thyroid hormones, melanin, adrenaline (epinephrine), noradrenaline (norepinephrine) and dopamine. The biosynthesis of some of these signalling molecules is described in Section 4.4. 

Tyrosine is structurally related to and derived from phenylalanine. It is the metabolic precursor to dopamine, an important neurotransmitter. Tyrosine is also the precursor to the hormones epinephrine and norepinephrine and to melanin, the pigment of skin. 

Epinephrine. Is adrenaline. This substance is highly psychotomimetic in small doses (1 to 5 mg), but is not orally active because enzymes in the stomach destroy its molecular structure. To keep from having to inject it, put a dose under your tongue and let it absorb into your blood stream in this manner. 

Since structural requirements for high affinity, on the one hand, and oral applicability, on the other, do not match, choosing a sympathomimetic is a matter of compromise. If the high affinity of epinephrine is to be exploited, absorbability from the intestine must be foregone (epinephrine, isoprenaline). If good bioavailability with oral administration is desired, losses in receptor affinity must be accepted (etilefrine). 

In terms of chemical structure, amphetamines are very close to epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine, differing in the absence of a hydroxyl group in the aromatic ring and in the aliphatic chain. 

The CL emission of Scheme 3 catalyzed by HRP can be applied to the quantitative analysis of catecholamines, such as dopamine (68), epinephrine (132), L-DOPA (30), norepinephrine (133), deoxyepinephrine (134) isoproterenol (135) and dihydroxybenzy-lamine (136), in a FIA system, after undergoing the oxidation shown for dopamine (68) in equation 20. The mechanism of this process is not totally clear however, the CL yields of equation 20 depend upon the pH of the system (pH 9 is convenient and is achieved by adjusting the concentration of imidazole), the temperature (60 °C is adequate) and the structure of the analyte (a calibration curve is needed for each one). Taking 68 as reference (100%) the CL yields after 30 min incubation (achieved by controlling the flow through a long capillary mbe) are as shown in equation 42 A5i... 

Many different receptor types are coupled to G proteins, including receptors for norepinephrine and epinephrine (a- and p-adrenoceptors), 5-hydroxytrypta-mine (serotonin or 5-HT receptors), and muscarinic acetylcholine receptors. Figure 2.1 presents the structure of one of these, the uz-adrenoceptor from the human kidney. All members of this family of G protein-coupled receptors are characterized by having seven membrane-enclosed domains plus extracellular and intracellular loops. The specific binding sites for agonists occur at the extracellular surface, while the interaction with G proteins occurs with the intracellular portions of the receptor. The general term for any chain of events initiated by receptor activation is signal transduction. 

In noradrenergic neurons, the end product is norepinephrine. In the adrenal medulla, the synthesis is carried one step further by the enzyme phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine. The human adrenal medulla contains approximately four times as much epinephrine as norepinephrine. The absence of this enzyme in noradrenergic neurons accounts for the absence of significant amounts of epinephrine in noradrenergic neurons. The structures of these compounds are shown in Figure 9.4. 

Adrenoceptors interact not only with norepinephrine but also with the adrenal medullary hormone epinephrine and a number of chemically related drugs. However, the responses produced by the drugs in different autonomic structures differ quantitatively or qualitatively from one another. 

The adrenomimetic drugs can be divided into two major groups on the basis of their chemical structure the catecholamines and the noncatecholamines. The catecholamines include norepinephrine, epinephrine, and dopamine, all of which are naturally occurring, and several synthetic substances, the most important of which is isoproterenol (isopropyl norepinephrine). The skele-... 

MAO A and B differ in primary structure and in substrate specificity [5,7]. The two isozymes, located on the mitochondrial outer membranes, have 70% homology in peptide sequence and share common mechanistic details. It is now recognized that these are different proteins encoded by different genes, but probably derived from a common ancestral gene. Crystal structures for both MAO A and B complexes with inhibitors have recently been reported [8]. Serotonin is selectively oxidized by MAO A, whereas benzylamine and 2-phenylethylamine are selective substrates for MAO B. Dopamine, norepinephrine, epinephrine, trypt-amine, and tyramine are oxidized by both MAO A and B in most species [9]. In addition, MAO A is more sensitive to inhibition by clorgyline (1), whereas MAO B is inhibited by low concentrations of L-deprenyl ((f )-( )-deprenyl) (2) [5,6cj. Development of inhibitors that are selective for each isozyme has been an extremely active area of medicinal chemistry [8]. 

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