Epinephrine, from tyrosine

Dopamine (5-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines norepinephrine and epinephrine from tyrosine in the adrenal medulla and central nervous system. During hy-droxylation, the Cu+ is oxidized to Cu " reduction back... 

The answers are 327-a, 328-c 329-d. (Hardman, pp 120, 250, 582-583.) Epinephrine is made from tyrosine in a series of steps through L-dopa, dopamine, NE, and finally epinephrine. The conversion of tyrosine to dopa by tyrosine hydroxylase is the rate-limiting step in this pathway. Epinephrine constitutes about 80% of the catecholamines in the adrenal medulla. The enzyme that synthesizes epinephrine from NE is also found in certain areas of the CNS. 

Catecholamine Epinephrine From tyrosine Plasma membrane receptors second messengers... 

Several other metabolic reactions require vitamin C as a cofactor. These include the catabolism of tyrosine and the s)mthesis of epinephrine from tyrosine and the synthesis of the bile acids. 

Tyrosine can be decarboxylated to tyramine by aromatic L-amino acid decarboxylase of intestinal bacteria. Tyramine, which is present in large amounts in certain foods (e.g., aged cheeses, red wines), is converted by monoamine oxidase (MAO) to the aldehyde derivatives. However, individuals who are receiving MAO inhibitors for the treatment of depression can accumulate high levels of tyramine, causing release of norepinephrine from sympathetic nerve endings and of epinephrine from the adrenal medulla. This results in peripheral vasoconstriction and increased cardiac output, which lead to hypertensive crises that can cause headaches, palpitations, subdural hemorrhage, stroke, or myocardial infarction. 

Figure 21.32 Biosynthesis of the catecholamines-dopamine, norepinephrine, and epinephrine-from tyrosine. 

In bacterial (Chromobacterium violaceum) pterin-dependent phenylalanine hydroxylase, a cupric ion is in a tetragonal coordination environment with several nitrogen donors [54]. Dopamine p-mo nooxygenase takes part in the biosynthetic pathway for the production of epinephrine from tyrosine [55] ... 

Epinephrine (also called adrenalin) is structurally related to the amino acid tyrosine. Epinephrine is released from the adrenal glands in response to stress (the fight or flight response). When it binds to specific receptors, it sets off a chain of events that leads to increased levels of glucose in the blood, increased glycolysis in muscle cells, and increased breakdown of fatty acids for energy. Glucagon (a peptide that contains 29 amino acid residues) is released by the... 

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

Catecholamines. The catecholamines, epinephrine (EPl adrenaline) (85), norepinephrine (NE noradrenaline) (86) (see Epinephrine and norepinephrine), and dopamine (DA) (2), are produced from tyrosine by the sequential formation of L-dopa, DA, NE, and finally EPl. EPl and NE produce their physiological effects via CC- and -adrenoceptors, a-Adrenoceptors can be further divided into CC - and a2-subtypes which in turn are divided... 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

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). 

Three amines—dopamine, norepinephrine, and epinephrine—are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constimtes about 80% of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ (about 80% of the total), and most of the rest is made in other nerve endings and reaches the target sites via the circu-... 

Known most famously for their part in the fight or flight response to a threat, challenge or anger, adrenaline (epinephrine) and dopamine from the adrenal medulla and noradrenaline (norepinephrine), mainly from neurones in the sympathetic nervous system are known collectively as catecholamines. Synthesis follows a relatively simple pathway starting with tyrosine (Figure 4.7). 

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 (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

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. 

Selective hydroxylation of some aromatic compounds can be achieved using HRP C in the presence of oxygen and dihydroxyfumaric acid (270). This process afforded l-DOPA from L-tyrosine, D-(-)-3,4-dihydroxy-phenylglycine from D-(—)-4-hydroxyphenylglycine, and L-epinephrine (adrenalin) from L-(-)-phenylephrine in yields of up to 70%. 

Epinephrine is a hormone synthesized in the adrenal glands from tyrosine (see p. 352). Its release is subject to neuronal control. This emergency hormone mainly acts on the blood vessels, heart, and metabolism. It constricts the blood vessels and thereby increases blood pressure (via ai and a2 receptors) it increases cardiac function (via P2 receptors) it promotes the degradation of glycogen into glucose in the liver and muscles (via P2 receptors) and it dilates the bronchia (also via P2 receptors). 

Corticosteroids also affect adrenomeduUary function by increasing epinephrine production the mechanism is exertion of a stimulatory action on two of the enzymes that regulate catecholamine synthesis, tyrosine hydroxylase, the rate-Umiting enzyme, and phenyl-ethanolamine Af-methyltransferase, which catalyzes the conversion of norepinephrine to epinephrine. Steroids also influence the metabolism of circulating catecholamines by inhibiting their uptake from the circulation by noimeuronal tissues (i.e., extraneuronal uptake see Chapter 9). This effect of corticoids may explain their permissive action in potentiating the hemodynamic effects of circulating catecholamines. 

Similarly, the effects of SNA on the catecholamine (norepinephrine, epinephrine, dopamine) systems have been widely studied, but the results are far from clear. SNA has been reported to Increase rat brain tyrosine and to decrease rat brain norepinephrine (NE) and to Increase dopamine (DA) slightly.Again, conflicting results are available.31 Apparently, changes In these biogenic... 

Dopamine, abbreviated DA, is a biosynthetic compound and neurotransmitter produced in the body from the amino acid tyrosine by several pathways. It is synthesized in the adrenal gland where it is a precursor to other hormones (see Epinephrine) and in several portions of the brain, principally the substantia nigra and hypothalamus. Dopamine is stored in vesicles in the brain s presynaptic nerve terminals. It is closely associated with its immediate precursor, L-Dopa (levodopa). Casmir Funk (1884—1967) first synthesized Dopa in racemic form... 

Catecholamine Hormones The water-soluble compounds epinephrine (adrenaline) and norepinephrine (noradrenaline) are catecholamines, named for the structurally related compound catechol. They are synthesized from tyrosine. 

Other important nitrogen-containing compounds made from amino acids include the catecholamines (dopamine, norepinephrine, and epinephrine), which are synthesized from tyrosine creatine, which is synthesized from arginine and glycine histamine, which is synthesized from histidine and serotonin, which is synthesized from tryptophan. 

Pathway of epinephrine synthesis. Epinephrine and its precursor, norepinephrine, are synthesized from tyrosine. The synthesis occurs in the chromaffin cells of the adrenal medulla and in neurons of the central and peripheral nervous system. The first step, which is catalyzed by tyrosine hydroxylase, is the rate-limiting step in the pathway. 

---