Biogenic amines, oxidative

The biogenic amines are the preferred substrates of MAO. The enzyme comes in two flavors, MAO-A and MAO-B, both of which, like FMO, rely on the redox properties of FAD for their oxidative machinery. The two isoforms share a sequence homology of approximately 70% (81) and are found in the outer mitochondrial membrane, but they differ in substrate selectivity and tissue distribution. In mammalian tissues MAO-A is located primarily in the placenta, gut, and liver, while MAO-B is predominant in the brain, liver, and platelets. MAO-A is selective for serotonin and norepinephrine and is selectively inhibited by the mechanism-based inhibitor clorgyline (82). MAO-B is selective for /1-phcncthylaminc and tryptamine, and it is selectively inhibited by the mechanism-based inhibitors, deprenyl and pargyline (82) (Fig. 4.32). Recently, both MAO-A (83) and MAO-B (84) were structurally characterized by x-ray crystallography. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

Psilocybin (Figure 3.5a) and psilocin (Figure 3.5b) are indole derivatives substituted in position 4 by a hydroxyl group, where psilocybin is phosphory-lated. Due to its ionic properties, psilocybin is soluble in water. In addition, phosphorylation protects psilocybin from oxidative degradation. Both compounds are found to affect laboratory animals, but there is evidence that only the dephosphorylated form, psilocin, is the active species. In their structure the toxins resemble serotonine, a biogenic amine known to be a neurotransmitter. 

HT) into the nerve terminal, the desmethylated metabolites show selectivity as noradrenaline uptake inhibitors. Thus no TCA can be considered to be selective in inhibiting the uptake of either of these biogenic amines. In the case of TCA overdose, the normal oxidative pathways in the liver are probably saturated, which leads to a disproportionately high concentration of the desmethylated metabolite. The practical consequence of this finding is that toxic plasma concentrations of a TCA are very likely to occur if the dose of the drug is increased in those patients who fail to respond to normal therapeutic doses of the drug. Such a transition to toxic doses could occur suddenly. 

The abundance of diverse oximes as naturally occurring products is attributed, in general, to complicated metabolic processes that include enzyme-induced oxidation of either amino acids or biogenic amines, as well as to the relatively low reactivity of oximes compared to HA. The co-occurrence of HA and a variety of carbonyl-containing molecules in plants and animals may also contribute to the formation of the oxime bond in nature. 

By analogy with the biogenesis of oximes via oxidation of amino acids or biogenic amines, the biosynthetic pathway for insertion of the ketoxime function into the antibiotic, nocardicin A (18), was shown to be dependent on the oxidation of the corresponding primary amine precursor of 18 by cytochrome PTSO ". Similarly, the formation of the ketoxime bond of verongamine (17) is attributed to the oxidation of a primary amine precursor . 

The pyrrolizidine nucleus is characteristic of this group of alkaloids. The a is either L-ornithine or L-arginine, and the /3 is a biogenic amine, the putrescine. Oxidative deamination by enzyme NAD+ converts two molecules of putrescine... 

Amine oxidases catalyze the oxidative deamination of both xenobiotic and biogenic amines, and thus have many critical biological functions. Two distinct classes differ in the nature of their prosthetic groups [1]. The flavin-(FAD flavin adenine dinucleotide)-dependent amine oxidases include monoamine oxidases (MAO A and B) and polyamine oxidases. Amine oxidases not containing FAD, the so-called semicarbazide-sensitive amine oxidases (SSAO), include both plasma amine oxidases and tissue amine oxidases. These contain quinonoid structures as redox cofactors that are derived from posttranslationally modified tyrosine or tryptophan side chains, topaoquinone frequently playing this role [2]. 

Biogenic amines, such as histamine [131], adenine [132], dopamine [133] and melamine [134], have been determined using chemosensors combining MIP recognition and PM transduction at QCM. Electronically conducting MIPs have been used in these chemosensors as recognition materials. Initially, functional electroactive bis(bithiophene)methane monomers, substituted either with the benzo-18-crown-6 or 3,4-dihydroxyphenyl, or dioxaborinane moiety, were allowed to form complexes, in ACN solutions, with these amines as templates. Subsequently, these complexes were oxidatively electropolymerized under potentiodynamic conditions. The resulting MIP films deposited onto electrodes of quartz resonators were washed with aqueous base solutions to extract the templates. 

The (S)-/ -Phe or (S)-/ -Tyr substructures of several spermidine alkaloids from plants, for example (S)-periphylline 43 [100, 101] or the spermine derivatives (S)-verbascenine 51 [101], aphelandrine 52 [102], chaenorhine 56 [103] and chae-norpine [104], hint at Michael addition of the biogenic amine to cinnamic acid 48 (or some oxidized equivalent, e.g. 49) within the /7-amino amide-forming step... 

The biological function of amine oxidases involves the oxidation of biogenic amines formed during normal biological processes. In mammals, the monoamine oxidases are involved in the control of the serotonin catecholamine ratios in the brain, which in turn influence sleep and EEG patterns, body temperature, and mental depression. Two groups of amine oxidases are involved in the oxidative deamination of naturally occurring amines as well as foreign compounds. 

Ceruloplasmin, a protein from the a-globulin fraction of human plasma, is usually considered to be the major copper transport protein. However, it also catalyzes the oxidation of biogenic amines, including catecholamines, adrenaline, noradrenaline, dopamine, and the indoleamine 5-hydroxytrypta-mine (5HT). 

Do optically active 1-methyl-TIQs, as sketched in Fig. 32 for the synthesis of (7 )-salsolinol, originate from a Pictet-Spengler reaction of dopamine with acetaldehyde derive from ethanol, or are they the result of a Pictet-Spengler reaction of biogenic amines with pyruvic acid, as sketched in Fig. 33 Based on the accumulated data it seems reasonable to propose that optically active TIQs are formed by the pyruvic acid pathway, and that the pyruvic acids may be derived from an impaired glucose metabolism or an impaired amino acid metabolism. Whether the intermediate TIQ-1-carboxylic acids 91a,b are enzymatically decarboxylated to afford 64a,b in a different enantiomeric ratio, or whether optically active TIQs are formed by oxidative decarboxylation of TIQ 91 to DIQ 120, followed by an asymmetric reduction, remains open to question. 

Flora, S.J.S., Saxena, G., Gautam, P., Kaur, P., Gill, K.D. (2007a). Lead induced oxidative stress and alterations in biogenic amines in different rat brain regions and their response to combined administration of DMSA and MiADMSA. Chem. Biol. Interact. 170 209-20. 

Monoamine oxidases (MAO-A and MAO-B) are mitochondrial enzymes that oxidatively deaminate endogenous biogenic amine neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine. MAOs are like EMOs in that they catalyze the oxidation of drugs to produce drug metabolites that are identical in chemical structures to those formed by CYPs. Because the resulting structures are... 

In neuronal function ROS play a role of metabolites immediately participating in the excitation process. In the intracellular space there are both enzymic (cyclooxygenases, monoamine oxidases) and non-enzymic (spontaneous oxidation of biogenic amines) reactions where they are formed. Mitochondrial respiratory chain also provides ROS production in a cell under conditions of changeable oxygen pressure [29,30]. 

Spontaneous or enzyme dependent oxidation of biogenic amines resulting in formation of SAR, and toxic aldehydes... 

Reviews on the isopavine alkaloids have appeared dealing with various synthetic approaches and with that using lead tetra-acetate oxidation in particular/ The preparation of a number of argemonine analogues (47) by transannular addition of various biogenic amines, e.g. 5-methoxytryptamine to the dione (48), has been reported/""... 

Table IX. Oxidative Deamination of Biogenic Amines by Bulb Mite Homogenates...

From the studies so far described it seemed that LSD was almost unique amongst centrally acting compounds in the potency of its effects on the caeruloplasmin-catalysed oxidation of NA and 5-HT, and this has led to the suggestion that this enzyme, or one with similar properties, may be directly involved in the mode of action of LSD. It is known that the Km values for NA and 5-HT are almost identical, suggesting that caeruloplasmin or an enzyme with similar properties could exercise a very sensitive control over the relative concentrations of these two amines (and probably also dopamine) in those parts of the brain where they act as neurotransmitters. If, as seems likely, the maintenance of a balance between NA, dopamine and 5-HT is essential to normal mental function, then LSD could produce its central effects by disturbing the balance between these biogenic amines as a result of its interaction with caeruloplasmin or a similar enzyme moreover, since LSD affects the... 

A considerable body of results accumulated during earlier decades from activity studies of hCp now awaits a more meaningful analysis using the available 3D structure. Catalysis of amine oxidation by hCp, in particular biogenic ones present in plasma, cerebral, spinal, and intestinal fluids as well as of ferrous ions, which is probably physiologically relevant, has been studied extensively (68, 71). The mechanism of dioxygen reduction by hCp at the trinuclear center is of particular interest, as the presence of three distinct Tl sites raises the question of which centers are involved in internal ET to the single O2 reduction site. This mechanistic question prompted us to initiate ET studies by PR. 

Figure 2-2 illustrates the irreversible inhibition of the flavine-enzyme monamine oxidase (MAO) by the antihypertensive agent pargyline. This enzyme is important in the catabolism of catechol- and other biogenic amines, including epinephrine and norepinephrine to their corresponding aldehydes. Equation 2.8 illustrates the oxidation of monamines by way of an imino intermediate while the oxidized flavine prosthetic group FAD is simultaneously reduced. 

---