Amine oxidase and

Hacisalihoglu A, JA Jongejan, JA Duine (1997) Distribution of amine oxidases and amine dehydrogenases in bacteria grown on primary amines and characterization of the amine oxidase from Klebsiella oxytoca. Microbiology (UK) 143 505-512. 

Semicarbazide Sensitive Amine Oxidase and Vascular Adhesion Protein-1 One Protein Being Validated as a Therapeutic Target for Inflammatory Diseases... 

Semicarbazide Sensitive Amine Oxidase and Vascular Adhesion Protein-1... 

Scheme 2.31 Deracemization of amines via combined use of an enantioselective amine oxidase and ammonia borane.

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]. 

In contrast to the substantial work with MAO, relatively little research has been reported on the mechanism of inhibition of copper-containing amine oxidases and SSAO by cyclopropylamines. Bovine plasma amine oxidase, equine plasma amine oxidase, Escherichia coii amine oxidase, and Arthrobacter globiformis amine oxidase were inhibited by frans-2-phenylcyclopropylamine (8a) and the mode of inhibition was shown by spectral and crystal structure analyses to be competitive and reversible [36,37,129],... 

A case in point. What happens when you put a methyl group on the two-position of the indole ring of a tryptamine. In the three examples, examples of the best studied tryptamines that were not active orally, they all became orally active. DMT, DET and 5-MeO-DMT, the three major parenterally-only active psychedelics, all blossomed into orally active compounds with the addition of a simple methyl group to that indole 2-position. As I had smugly argued, in the discussions of 2-Me-DMT, 2-Me-DET and Indapex, it is as if that bit of bulk got in the way of the destructive amine oxidases, and protected the molecule from its expected first-pass metabolic destruction. 

The paramagnetic copper present in the non-blue oxidases such as galactose oxidase and amine oxidases, and also in the blue oxidases, has d-d and ESR spectra typical of coordination complexes of copper(II). 

Concentrations of tyramine and histamine were similar that of angiotonin is estimated. The preparation, which contained active amine oxidase and no other oxidases, was supplied by Karl Folkers of Merck and Company. Data were obtained from C. C. Stock, to whom the author is indebted. 

Lower curve (rat 183). Effect of a double dose of angiotonin mixed with amine oxidase and shaken for 30 minutes at room temperature. Angiotonin was completely inactivated. After 4 minutes the same dose alone produced a modified pressor response. Rat was hypertensive. 

The N-terminal stalk domain(Dl) is not present in all amine oxidases and consists of a five-stranded antiparallel ()-sheet twisted round an a-helix. The P-sheets from the two stalk domains face towards the molecular diad axis but are not tightly packed together. The biological role of D1 is unknown. 

The Copper Site. In a crystal form of ECAO shown to contain catalytically-active protein (Parsons et al., 1995), the eopper is penta-coordinated in approximate square pyramidal eonfiguration by four basal (equatorial) ligands (His 524, His 526, His 689 and a water [We]) and an apical (axial) water (Wa). The presence of equatorial and axial waters had been first reported by Barker et al. (1979) from EPR, water proton relaxation and kinetic studies on pig plasma amine oxidase and the prediction of histidines and waters as the copper ligands came from EXAFS studies by Scott and Dooley (1985). The equatorial water (We) is labile and not always present. In the HP AO structure (Li et al., 1998) it is present in some, but not all, of the six independent subunits in the same erystal. A comprehensive discussion of the spectroscopic properties of the copper site in amine oxidases, including the exchange rates for the equatorial and axial waters, is given in the review by Knowles and Dooley (1994). 

Stopped flow kinetic studies by Hartmann and Klinman (1991) on bovine serum amine oxidase and by Olsson et al. (1976) on pig plasma amine oxidase showed that the substrate Schiff-base has an absorbance maximum at 350nm. 

It is safe to predict that there will be major effort in understanding the biological roles of copper-containing amine oxidases and the relationship to flavin-containing amine oxidases. The diversity of amine oxidases in all forms of life and their involvement in key cellular processes in plants and mammals underline the importance of this objective. 

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