Catechol-amine neurotransmitters

Phenylalanine hydroxylase [39] catalyzes the first step of phenylalanine degradation in mammals. Phenylalanine is converted into tyrosine (Scheme XI.9). The enzyme has one tightly bound, non-heme iron atom per subunit. Tyrosine hydroxylase catalyzes [40] the hydroxylation of tyrosine to produce dihydroxy-phenylalanine (DOPA), the first step in the biosynthesis of catechol-amine neurotransmitters (Scheme XI.9). This enzyme also contains one ferrous iron atom per subunit. These two enzymes, together with tryptophane hydroxylase (Scheme XI.9) [41], constitute a family of tetrahydropterin-dependent aromatic acid hydroxylases (monooxygenases) [42], Other dioxygenases catalyze the hydroxylation ofarenes [43],... 

Catecholamine neurotransmitters are subsequently inactivated by enzymic methylation of the 3-hydroxyl (via catechol-O-methyltransferase) or by oxidative removal of the amine group via monoamine oxidase. Monoamine oxidase inhibitors are sometimes used to treat depression, and these drugs cause an accumulation of amine neurotransmitters. Under such drug treatment, simple amines such as tyramine in cheese, beans, fish, and yeast extracts are also not metabolized and can cause dangerous potentiation of neurotransmitter activity. 

Dopamine, the free catechol corresponding to (1-1), plays an important role as a neurotransmitter, particularly in the CNS. The synthesis of a dopamine-related sedative agent starts with the condensation of homoveratramine (1-1) with styrene oxide (1-2) to afford the carbinol (1-3). Treatment of that product with a strong acid leads to an attack on the electron-rich aromatic ring by the resulting carbocation there is thus obtained the benzazocine (1-4). The secondary amine is then methylated by reaction with formaldehyde and formic acid to yield trepipam (1-5) [1]. 

Epinephrine (see Figure 1) is synthesized in several steps from either phenylalanine or tyrosine (both amino acids). Two adjacent hydroxyl groups are placed on the aromatic ring, leading to the ring structure called catechol. These hydroxylations form the intermediate L-dopa, which in turn is converted to dopamine (a neurotransmitter), norepinephrine (also a neurotransmitter), and finally epinephrine. Epinephrine together with norepinephrine and dopamine make up the family of biogenic amines called catecholamines. 

Description Catecholamine is the name of a group of compounds that contain a catechol nucleus (a benzene ring with two adjacent hydroxyl substituents) and an amine group. This group includes the mammalian neurotransmitters or hormones, such as dopamine, norepinephrine, and epinephrine, and nonmammalian compounds such as octopa-mine. Each compound has its own synonyms. Representative Chemical Dopamine Chemical Abstracts Service Registry Number CAS 51-61-6... 

The constant potential amperometric detector determines the current generated by the oxidation or reduction of electoactive species at a constant potential in an electrochemical cell. Reactions occur at an electrode surface and proceed by electron transfer to or from the electrode surface. The majority of electroactive compounds exhibit some degree of aromaticity or conjugation with most practical applications involving oxidation reactions. Electronic resonance in aromatic compounds functions to stabilize free radical intermediate products of anodic oxidations, and as a consequence, the activation barrier for electrochemical reaction is lowered significantly. Typical applications are the detection of phenols (e.g. antioxidants, opiates, catechols, estrogens, quinones) aromatic amines (e.g. aminophenols, neuroactive alkaloids [quinine, cocaine, morphine], neurotransmitters [epinephrine, acetylcoline]), thiols and disulfides, amino acids and peptides, nitroaromatics and pharmaceutical compounds [170,171]. Detection limits are usually in the nanomolar to micromolar range or 0.25 to 25 ng / ml. 

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