Intestinal hydrolase activity

Drugs may also undergo hydrolysis by intestinal esterases (hydrolases), more specifically carboxylesterases (EC 3.1.1.1) in the intestinal lumen and at the brush border membrane [58, 59]. It has been shown that intestinal hydrolase activity in humans was closer to that of the rat than the dog or Caco-2 cells [60]. In these studies, six propranolol ester prodrugs and p-nitrophenylacetate were used as substrates, and the hydrolase activity found was ranked in the order human > rat Caco-2 cells > dog for intestinal microsomes. The rank order in hydrolase activity for the intestinal cytosolic fraction was rat > Caco-2 cells = human > dog. The hydrolase activity towards p-nitrophenylacetate and tenofovir disoproxil has also been reported in various intestinal segments from rats, pigs and humans. The enzyme activity in intestinal homogenates was found to be both site-specific (duodenum > jejunum > ileum > colon) and species-dependent (rat > man > Pig)-... 

BHANDARI s D, GREGORY J F 3rd (1990) Inhibition by selected food components of human and porcine intestinal pteroylpolyglutamate hydrolase activity. ,4m J Clin Nutr. 51 87-94. 

Yoshigae, Y., Imai, T., Horita, A., Matsukane, H., Otagiri, M., Species differences in stereoselective hydrolase activity in intestinal mucosa, Pharm. Res. 1998, 35, 626-631. 

Figure 14 Species differences in hydrolase activity of liver and small intestine microsomes.

Microsomal epoxide hydrolase activities are listed in Table IX. There was significantly higher (0.05 level) hepatic microsomal epoxide hydrolase activity in pectin-,Metamuoil-, and cellulose-treated rats, as compared to control-, lignin- and Lab Chow-fed animals. There was no significant difference in intestinal microsomal epoxide hydrolase activities among any of the treatment groups. 

Table IX. Epoxide Hydrolase Activities in Liver and Intestinal Mucosa...

De Jong, B. J., and Hulsmann, B. C. (1978) Monoacylglycerol Hydrolase Activity of Isolated Rat Small Intestinal Cells, Biochim. Biophys. Acta 27, 36-46. 

Yoshigae Y, Imai T, Aso T, Otagiri M. Species differences in the disposition of propranolol prodrugs derived from hydrolase activity in intestinal mucosa. Life Sci 1998 62 1231-1241. 

Dietary retinyl esters, retinol, and provitamin A carotenoids are dispersed and emulsified in the stomach during the gastric phase of lipid digestion. They then enter the lumen of the duodenum where extensive hydrolysis of retinyl esters takes place. In infants, the bile salt-stimulated lipase in human milk may play a role in retinyl ester hydrolysis in the duodenum (Fredrikzon et al., 1978). The major retinyl ester hydrolase activity that acts in the intestines is, however, derived from the pancreas. 

EE Sterchi, JF Woodley. Peptide hydrolases of the human small intestinal mucosa Distribution of activities between brush border membranes and cytosol. Clin Chim... 

The /V4-acylatcd sulfonamides, succinylsulfathiazole (4.124) and phtha-lylsulfathiazole (4.125), are poorly absorbed by the gastrointestinal tract. These compounds, which were once used as intestinal antiseptics, are inactive in vitro and must be activated by hydrolysis to sulfathiazole by bacterial hydrolases in the large intestine [78],... 

Of the dichloroacetamides diloxanide furoate, clefamide, teclozan and etofamide the most frequently used agent is diloxanide furoate. It is the luminal amoebicide of choice in chronic intestinal amoebiasis, however it lacks efficacy acute intestinal amoebiasis. Its mechanism of action is unknown. Given orally, diloxanide is formed by bacterial hydrolases. Diloxanide is for 90% absorbed and then metabolized to diloxanide glucuronide. The remaining 10% remains in the intestine as the active drug. Diloxanide is generally well tolerated. Adverse effects include flatulence, nausea and abdominal cramps. 

Pancreatic lipase, in the presence of bile salts and coUpase, acts at the oil-water interface of the triglyceride emulsion to produce fatty acids and 2-monoacylglycerols. Cohpase is secreted in pancreatic juice as an inactive proenzyme, which is converted to the active form by trypsin. Other significant enzymes involved in the breakdown of fats within the intestinal lumen are cholesterol ester hydrolase, phospholipase A, and a nonspecific bile salt-activated lipase. 

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