Applications of Diamine Oxidase

Posted by Iva Colter on September 23rd, 2022

Diamine oxidase (DAO) is an intracellular enzyme that catalyzes diamine in mucosal or ciliated epithelial cells of the mammalian small intestine. It protects the intestinal mucosa by regulating intracellular ion homeostasis, influencing conduction pathways, and promoting cellular repair. Serum DAO is elevated in small intestinal mucosal barrier failure or in intestinal mucosal cell necrosis; therefore, DAO activity in blood can reflect the state of intestinal injury. It also has some significance in the diagnosis of chronic urticaria quick-onset reaction, multi-organ dysfunction syndrome, and pre-term abortion.

The amino acid sequence of human DAO consists of 751 amino acid residues and its molecular weight is 250,000, which is an enzyme containing copper and pyridoxal phosphate. Its gene sequence contains five exons, except for the first exon which is very short and does not encode a sequence, the other four express amino acid sequences respectively. The active site was shown to be highly expressed in dividing cells by the second exon (524-618).  The pH optimum of DAO is 7-9 and varies with substrate. The enzyme activity can be inhibited by heavy metal ions, hydroxylamine, cyanide, carbonyl reagents such as aminourea, and sulfhydryl compounds.

Applications

1. The effect of enteral nutrition on intestinal mucosal injury and repair in early stage

Scientists investigated the mechanism of early enteral nutrition on intestinal mucosal damage and repair in burned rats. It was demonstrated that the ITF content was negatively correlated with plasma DAO activity (r=-0.964), and the blood DAO concentration increased dramatically when the intestinal mucosa was damaged. Structural damage to the intestinal mucosa is associated with a decreased ability of the intestine to synthesize and secrete ITF. Enteral nutrition elevates ITF concentration and decreases DAO activity after high injury, and ITF is of better value than intravenous nutrition in repairing damaged intestinal mucosa.

2. Role in post-traumatic intestinal barrier function impairment

Several scientists have studied the intestinal barrier function impairment and its protective mechanism in various trauma animal models and clinical burn patients. The analysis of intestinal barrier function changes in post-trauma animal models showed that small intestinal DAO activity was negatively correlated with plasma DAO activity, and changes in blood DAO activity reflected intestinal injury, and the changes were correlated with plasma endotoxin levels and bacterial translocation. The stress response produced by intestinal ischemia-reperfusion injury makes the trend and degree of change after injury different. Pre-emptive protection of intestinal barrier function is important to prevent the development of systemic inflammatory response (SIRS) to MODS induced by intestinal-derived bacterial and toxin translocation.

3. Application in the diagnosis and prognosis determination of small intestinal clonorchiasis

Small bowel clonorchiasis is an inflammatory disease of the intestine of unknown origin. It and chronic non-specific ulcerative colitis are collectively known as inflammatory bowel disease (IBD). The disease is active with shortening and thickening of the villi and deep ulceration and necrosis of epithelial cells, causing pathological changes such as reduction in mucosal area and abnormal function. Serum DAO activity in patients with small bowel clonorchiasis is altered and correlates with the extent of the lesion before changes are detected on imaging. Serum DAO activity is lower in patients with small bowel clonorchiasis than in patients with ulcerative colitis and colonic clonorchiasis, and its activity is negatively correlated with the severity of the disease.

In addition to decomposing histamine, diamine oxidase also decomposes amines generated by decarboxylation of amino acids in the intestinal mucosa and plays a detoxifying role. Its crystallization has been obtained from the enzyme in ruminant plasma, which oxidizes benzylamine and spermine well, with a molecular weight of 250,000 and containing copper and pyridoxal phosphate. The enzyme from plants also oxidizes monoamines well, contains copper and is pink in color. Enzymes of microorganisms also have a high specificity for the substrate.