Epinephrine biological importance

The first in-depth study of the electrooxidation mechanism of a biologically important catecholamine was that of Hawley and co-workers who investigated the bahavior of epinephrine (3). This compound, often called adrenaline. 

The enzymatic introduction of a functional group into a biologically important molecule is not only specific with regard to the location at which the reaction occurs in the molecule (see Chapter 4, Problem 50), but also usually specific in the stereochemistry obtained. The biosynthesis of epinephrine first requires that a hydroxy group be introduced specifically to produce (—(-norepinephrine from the achiral substrate dopamine. (The completion of the synthesis of epinephrine wdl be presented in Problem 71 of Chapter 9.) Only the (—) enantiomer is functional in the appropriate physiological manner, so the synthesis must be highly stereoselective. 

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. 

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. 

The catecholamines dopamine, norepinephrine and epinephrine are neurotransmitters and/or hormones in the periphery and in the CNS. Norepinephrine is a neurotransmitter in the brain as well as in postganglionic, sympathetic neurons. Dopamine, the precursor of norepinephrine, has biological activity in the periphery, most particularly in the kidney, and serves as a neurotransmitter in several important pathways in the CNS. Epinephrine, formed by the N-methylation of norepinephrine, is a hormone released from the adrenal gland, and it stimulates catecholamine receptors in a variety of organs. Small amounts of epinephrine are also found in the CNS, particularly in the brainstem. 

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. 

The methyl group on methionine is activated when methionine is converted to S-adenosyl-methionine. It is the methyl group of 5-adenosylmethionine that is the immediate donor in biological methylations. Important reactions in which 5-adenosylmethionine acts as the methyl donor are the synthesis of creatine, epinephrine, and phosphatidylcholine. 

THE AROMATIC FAMILY The aromatic family of amino acids includes phenylalanine, tyrosine, and tryptophan. Of these, only tyrosine is considered to be nonessential in mammals. Either phenylalanine or tyrosine is required for the synthesis of dopamine, epinephrine, and norepinephrine, an important class of biologically potent molecules referred to as the catecholamines (Special Interest Box 14.2). Tryptophan is a precursor in the synthesis of NAD+, NADP+, and the neurotransmitter serotonin. 

The two most prominent one-carbon carriers are THF (the biologically active derivative of folic acid) and S-adenosymethionine (SAM). THF plays important roles in the synthesis of several amino acids and the nucleotides. SAM is a methyl donor in the synthesis of numerous biomolecules, for example, phosphatidylcholine, epinephrine, and carnitine. 

Hormones have several important functions in the body. They help maintain homeostasis, the balance of biological activities in the body. The effect of insulin in keeping the blood glucose level within narrow limits is an example of this function. The operation of epinephrine and norepinephrine in the fight-or-flight response is an example of the way in which hormones mediate responses to external stimuli. Finally, hormones play roles in growth and... 

A specific example of a biological methylation reaction that uses SAM is the conversion of noradrenaline (norepinephrine) to adrenaline (epinephrine). The reaction uses SAM to provide the methyl group. Noradrenaline and adrenaline are hormones that stimulate the breakdown of glycogen—the body s primary fuel source (see page 1041). You may have felt this adrenaline msh when preparing for a challenging activity. Adrenaline is about six times more potent than noradrenaline. This methylation reaction, therefore, is very important physiologically. 

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