Distribution and properties of human intestinal diamine oxidase and its relevance for the histamine catabolism

Abstract

High activities of diamine oxidase (EC 1.4.3.6) were measured in the intestinal tract of human subjects and of several mammalian species. The enzyme was localized in the mucosa and was distributed primarily in the cytoplasm; the only exception being the guinea-pig where it was located in the particulate fraction. Despite its instability the enzyme from human colonic mucosa was purified 80-fold. During the purification a soluble monoamine oxidase (EC 1.4.3.4) was separated from diamine oxidase. The pH optima of diamine oxidase for putrescine and histamine were 6.6–7.0 and 6.4–6.6, rspectively. Short-chain alipathic diamines were deaminated with the highest reaction velocity, but histamine and N τ -methylhistamine were also excellent substrates. The K m for putrescine was 8.3·10 −5 M, for histamine 1.9·10 −5 M for N τ -methylhistamine 9.7·10 −5 M. Typical substrates of monoamine oxidase were not deaminated by the enzyme. Aminoguanidine strongly inhibited human intestinal diamine oxidase (IC 50 = 1.1·10 − M). Because of its properties the intestinal diamine oxidase is considered to play a protective role against histamine in diseases such as ischaemic bowel syndrome, mesenteric infarction and ulcerative colitis.