IAP

What is IAP protein?

Intestinal alkaline phosphatase (IAP) is a glycoprotein consisting of a polypeptide chain with a molecular weight of about 40-50 kDa. Its active site consists of an alkaline phosphatase domain and a C-type domain. It mainly exists in the microvilli of small intestinal mucosal cells, especially in the epithelial cells of duodenum and jejunum. It is also found in some other tissues, such as bone, liver and placenta.

What is the function of IAP protein?

The main function of IAP is to catalyze the hydrolysis of phosphate, convert phosphate into inorganic phosphorus and organic phosphate, help intestinal absorption and regulate intestinal immune response. By hydrolyzing phosphate, it promotes the absorption of minerals such as calcium, iron, and magnesium. In tissues such as bone, liver and placenta, it is also involved in bone growth and metabolic processes, helping to maintain a healthy state of bones.

Fig1. Beneficial actions of IAP on the intestinal barrier. (Chenzhe Gao, 2024)

IAP Related Signaling Pathway

Although it may be involved in some signaling pathways within the cell, no signaling pathway has been found that it is directly involved. The function of intestinal alkaline phosphatase is mainly related to its enzyme activity and structural characteristics, which can catalyze the hydrolysis of phosphate and convert phosphate into inorganic phosphorus and organic phosphate.

IAP Related Diseases

The IAP protein expressed in bone is related to bone metabolic disorders such as osteoporosis and osteomalacia. In the liver and gallbladder system, it is associated with biliary obstruction, cholecystitis, cirrhosis and other hepatobiliary diseases. It is also associated with inflammatory bowel disease, intestinal malabsorption and other intestinal diseases.

Fig2. IAP as an indicator of intestinal barrier related disease assessment. (Chenzhe Gao, 2024)

Bioapplications of IAP

IAP is involved in the process of digestion and absorption of phosphates in food, so it can be used to assess the nutritional status of patients. At the same time, it can also be used as a monitoring index of small intestine disease, liver and bile system disease, bone metabolism and so on.

Case study 1: Dagmara Wojcik-Grzybek, 2024

Intestinal alkaline phosphatase (IAP) is an enzyme that plays a protective role in the gut. This study investigated the effect of IAP treatment on experimental colitis in mice subjected to forced exercise on a high-fat diet. C57BL/6 mice with TNBS colitis were fed a high-fat diet and subjected to forced treadmill exercise with or without IAP treatment.

Disease activity, oxidative stress, inflammatory cytokines, and gut microbiota were assessed. Forced exercise exacerbated colitis in obese mice, as evidenced by increased disease activity index (DAI), oxidative stress markers, and proinflammatory adipokines and cytokines. IAP treatment significantly reduced these effects and promoted the expression of barrier proteins in the colonic mucosa. Additionally, IAP treatment altered the gut microbiota composition. IAP treatment ameliorates the worsening effect of forced exercise on murine colitis by attenuating oxidative stress, downregulating proinflammatory biomarkers, and modulating the gut microbiota.

Fig1. The changes in DAI score, body weight (in grams) and relative skeletal muscle grip strength (expressed in Newton (N) per kilogram of body weight) of mice with colitis fed an SD or an HFD and forced to partake in treadmill exercise, with or without IAP administration.

Fig2. PAS staining) obtained from TNBS colitis mice fed an SD or HFD and forced to participate in treadmill (T) running with or without IAP administration as assessed at day 5 from colitis induction.

Case study 2: Zhen Luo, 2023

Heatstroke (HS) is a severe acute disease related to gastrointestinal barrier dysfunction, systemic inflammation and multiple organ injury. Many of the functions of Intestinal alkaline phosphatase (IAP) have been linked to gut homeostasis, gut barrier function and inflammation. However, the protective effect of IAP on heatstroke is not fully elucidated. This study aims to explore the protective effect of IAP on heatstroke by maintaining intestinal barrier and improving permeability. Then heat exposed mice (n = 195) were divided into three groups: 0.2 mL of 0.9 % physiological saline (HS) or vehicle (HS + Vehicle) or 300 IU IAP (HS + IAP) by gavage at 0, 24, and 48 h after onset. Control group mice (Con) (n = 65) were not exposed to heat and were gavaged with 0.9 % physiological saline of the same volume at the same time.

IAP treatment significantly reduced the levels of endotoxin, FD4, and D-lactate in the blood of heatstroke mice, reduced intestinal permeability and maintained the integrity of the intestinal barrier by increasing the expression of tight junction proteins. Meanwhile, IAP treatment alleviated liver and kidney damage caused by heatstroke, reduced serum levels of inflammatory cytokines, and thus improved survival rate of mice after heatstroke.

Fig3. Survival rates (%) of mice in the Con group, HS group, HS + Vehicle group, and HS + IAP group are shown at 120 h after HS.

Fig4. Representative laser confocal images of ileum samples in the Con group, HS group, HS + Vehicle group, and HS + IAP group, which were immunostained with occludin antibodies.

IAP has several biochemical functions, for example, . Some of the functions are cooperated with other proteins, some of the functions could acted by IAP itself. We selected most functions IAP had, and list some proteins which have the same functions with IAP. You can find most of the proteins on our site.

IAP has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with IAP here. Most of them are supplied by our site. Hope this information will be useful for your research of IAP.