Biomaterial Database

Inhibition of six copper-containing amine oxidases by the antidepressant drug tranylcypromine. 2003

Eric M Shepard, and Heather Heggem, and Gregory A Juda, and David M Dooley

Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA.

Potential inhibitory effects of the clinically utilized monoamine oxidase inhibitor tranylcypromine (TCP) on mammalian, plant, bacterial, and fungal copper-containing amine oxidases have been examined. The following enzymes have been investigated: human kidney diamine oxidase (HKAO), bovine plasma amine oxidase (BPAO), equine plasma amine oxidase (EPAO), pea seedling amine oxidase (PSAO), Arthrobacter globiformis amine oxidase (AGAO), and Pichia pastoris lysyl oxidase (PPLO). Only BPAO, EPAO, and AGAO were found to lose significant levels of activity when incubated with varying amounts of TCP. Inhibition of BPAO was completely reversible, with dialysis restoring full activity. TCP inhibition of AGAO was also found to be ultimately reversible; however, dialysis did not remove all bound compounds. Chemical displacement with either substrate or a substrate analogue successfully removed all bound TCP, indicating that this compound has a high affinity for the active site of AGAO. The notable lack of TCP inhibition on HKAO argues against the inhibition of diamine oxidase as a potential source for some of the deleterious side effects occurring in patients treated with this antidepressant. The marked differences observed in behavior among these enzymes speaks to the importance of intrinsic structural differences between the active sites of copper amine oxidases (CAO) which affect reactivity with a given inhibitor.

UI	MeSH Term	Description	Entries
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D010659	Phenylhydrazines	Diazo derivatives of aniline, used as a reagent for sugars, ketones, and aldehydes. (Dorland, 28th ed)
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006631	Amine Oxidase (Copper-Containing)	A group of enzymes including those oxidizing primary monoamines, diamines, and histamine. They are copper proteins, and, as their action depends on a carbonyl group, they are sensitive to inhibition by semicarbazide.	Diamine Oxidase,Histaminase,Amine Oxidase, Copper-Containing,Copper Amine Oxidase,Diaminobenzidine Oxidase,Semicarbazide-Sensitive Amine Oxidase,Xylylene Diamine Oxidase,Amine Oxidase, Copper,Amine Oxidase, Copper Containing,Amine Oxidase, Semicarbazide-Sensitive,Copper-Containing Amine Oxidase,Diamine Oxidase, Xylylene,Oxidase, Copper Amine,Oxidase, Copper-Containing Amine,Oxidase, Diamine,Oxidase, Diaminobenzidine,Oxidase, Semicarbazide-Sensitive Amine,Oxidase, Xylylene Diamine,Semicarbazide Sensitive Amine Oxidase
D000928	Antidepressive Agents	Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.	Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D001596	Benzylamines	Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.	Phenylmethylamine,alpha-Aminotoluene,alpha Aminotoluene
D013057	Spectrum Analysis	The measurement of the amplitude of the components of a complex waveform throughout the frequency range of the waveform. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Spectroscopy,Analysis, Spectrum,Spectrometry
D014191	Tranylcypromine	A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)	Jatrosom,Parnate,Transamine,Tranylcypromine Sulfate,trans-2-Phenylcyclopropylamine,Sulfate, Tranylcypromine,trans 2 Phenylcyclopropylamine