Inhibition of plant and mammalian diamine oxidase by substrate analogues

Abstract

Imidazoles, aliphatic substrate analogues and the natural dipeptides, carnosine and anserine, were investigated as inhibitors of diamine oxidase from the pig kidney, human pregnancy plasma and pea seedlings. Imidazole, methylimidazoles, N-acetylimidazole, histamine and N tau-methylhistamine are relatively potent inhibitors of mammalian diamine oxidase showing no influence on plant enzymes. Anserine and carnosine are inhibitors of pig kidney and pea seedling enzymes. Ki values are 2 microM and 10 microM respectively. Investigated natural derivatives of putrescine and cadaverine have no influence on diamine oxidase of different origin. In conclusion, we present some evidence to suggest that mammalian diamine oxidase, despite a high reaction rate with putrescine, is better adapted to histamine oxidation, whereas for plant enzymes the diamines are preferred substrates.

Diamine oxidase in the hen

“…This is clearly less than previously found in humans by using other methods, but reasonable as compared with recent mass-spectrometric findings on tele methylhistamine, the respective metabolite of histamine (SWAHN and SEDVALL, 1981) [5]. Elevated histamine levels in the CSF of MS patients have also been reported by MOLN.~.R and MOLDAV.…”

“…The influence of imidazole on putrescine oxidation by hen and rat intestinal enzymes indicates that histamine may have access to active centre of both enzymes. This is not the case with pea seedling enzyme, which is more adapted to putrescine as a substrate [5]. The sensitivity of hen and other [5] diamine oxidases to such inhibitors as carnosine and anserine in physiological concentrations may be of importance in the regulation of histamine levels by these natural dipeptides.…”

“…This is not the case with pea seedling enzyme, which is more adapted to putrescine as a substrate [5]. The sensitivity of hen and other [5] diamine oxidases to such inhibitors as carnosine and anserine in physiological concentrations may be of importance in the regulation of histamine levels by these natural dipeptides. The effect of these dipeptides on histamine metabolism seems to be complementary to the close relationship between the levels of carnosine and histamine already described 124, 25[.…”

“…The oxidative deamination of cadaverine by diamine oxidase yields 6-aminovaleraldehyde which cyclizes to Al-piperideine [5]. Using radioactive cadaverine as substrate for diamine oxidase measurement of the amount of ~4C-Al-piperideine formed was a procedure devised for estP mating diamine oxidase levels [6].…”

Histamine and histamine intolerance

“…Orally ingested histamine has been shown to aggravate eczema in AE patients in a DBPC provocation (112). A feedback inhibition of DAO through its degradation product imidazole acetic acid (113,114) or substrate inhibition (115,116) caused by the elevated histamine concentrations in AE may be a pathomechanism of a reduced histamine degradation capacity in a subgroup of patients with AE.…”