Gastric enzymes

D) The gastric enzymes needed to convert R-warfarin into S-warfarin are unstable near plastic. 

In the stomach, compounds are mixed with food, acid, gastric enzymes, and bacteria. All of these can alter the toxicity of the chemical, either by influencing absorption or by modifying the compound. It has been demonstrated that there are quantitative differences in toxicity, depending upon whether compounds are administered with food or directly into the empty stomach (Worden and Harper, 1963). 

Some metabolism of ethanol by ADH occurs in the stomach in men, but a smaller amount occurs in women, who appear to have lower levels of the gastric enzyme. This difference in gastric metabolism of alcohol in women probably contributes to the sex-related differences in blood alcohol concentrations noted above. 

Peptides, when administered orally, are susceptible to degradation in the stomach by gastric enzymes and the proteinases of the pancreas and brush border of the small intestine. Their lifetimes in the plasma are often short due to rapid proteolysis and other metabolic processes. Early efforts were made to improve the resistance of renin inhibitors to hydrolysis in vivo by the use of blocking groups at the Eland C-terminii [39] and replacement of susceptible peptide bonds other than the renin cleavage site. Studies of SAR have shown that various N- and C-terminal groups, some based on the morpholine nucleus and derivatives of it, have a favorable effect on the duration of inhibition in the... 

Pharmacokinetics The enzyme must be administered either IV or IM because it is destroyed by gastric enzymes. Disposition remains undefined. 

Gastric enzymes such as pepsin and trypsin convert proteins from food into the smaller peptide molecules, which in turn are converted into amino acids. 

The ascaris pepsin inhibitor-3 is an aspin, which is a family of inhibitors of aspartic proteases that protect worms from host gastric enzymes. Like the cystatins, the aspins are competitive inhibitors that bind in the substrate-binding subsites, but they do not have an amide bond that is available for nucleophilic attack. They gain most of their inhibitory activity by inserting their 3 N-terminal residues in the ST-S3 subsites of the protease (6) (Fig. 3). 

Fischer s laboratory was also involved in the use of gastric enzymes to prepare natural peptides for comparison with those synthesized by his collaborators, and to test the proteinlike nature of his synthetic products. Given the fact that the dogma of the day held that proteins were compounds with molecular weights of several thousand, organic chemists thought that the total synthesis of a protein was within reach. In retrospect, even if the... 

When testing for B 2 absorption by the gut, a test for hoitvTCIl and apo-TCII has an advantage over the S chilling test. The Schilling test uses pure vitamin Bx, as a component of the test protocol. Because of this, the Schilling test cannot detect defects in B]2 absorption due to the lack of stomach acid or the lack of activity of gastric enzymes. The TCII test is sensitive to the these problems, but also to the lack of intrinsic factor Herbert et al., 1990). 

Pancreatic lipase is one of the mammalian key digestive enzymes. It completes the dietary triacylglycerol breakdown initiated by preduode-nal lipases, including lingual and gastric enzymes, (see below). The enzyme is inhibited in the intestine by bile salts, but the activity is restored in the presence of colipase (CLP), a relatively short (95 residues) heat-stable polypeptide secreted by the pancreas (Semeriva and Desnuelle, 1979 Borgstrbm and Erlanson-Albertsson, 1984). The structural details of the interaction of colipase with lipase are described in Section III,C. 

The inhibition of hLAL by boronic acids and diethyl p-nitrophenyl phosphate (Sando and Rosenbaum, 1985 G. N. Sando and H. L. Brockman, unpublished, cited by Anderson and Sando, 1991) indicates that hLAL is a serine hydrolase. Two lipase/esterase consensus pentapep-tides, G-X-S-X-G, are found, but only one of them appears to be consistent with the packing requirements of the )8-eSer-a nucleophilic motif (see above). Susceptibility of the enzyme to sulfhydryl reagents, and the requirement of thiols for the stability of purified hLAL, prompted Anderson and Sando (1991) to propose that a cysteine residue, or rather a Cys/Ser couple, may be involved in an internal transacylation reaction. It must be pointed out, however, that hLAL has all three cysteines of the gastric enzyme (as well as six additional ones), and so the inhibitory Cys is also there. The same argument proposed herein with respect to hGL, i.e., that a free cysteine is topologically close to the active site, also holds for hLAL. 

Biochemical etiology Primarily, NSAID inhibition of a gastric enzyme (COX-1) required for synthesis of prostaglandins that have a protective effect on the gastric mucosa. A contributory factor is direct mucosal damage due to the acidic chemistry of NS AlDs. 

DON and its derivatives like D3G can resist to acidic conditions in the human stomach and are not cleaved by gastric enzymes... 

Pepsin is a gastric enzyme which hydrolyses proteins. It is secreted by the stomach as its inactive precursor, pepsinogen. This is converted to pepsin by the action of gastric acid. 

During digestion some of the chloride of the blood is used for the formation of hydrochloric acid in the gastric glands and is secreted into the stomach where it functions temporarily with the gastric enzymes and is then reabsorbed into the bloodstream with other nutrients. 

Where zymogens have been sequenced, the abbreviations of the zymogens are preceding lines containing proparts of the structure. After residue 77, all structures are named by abbreviated form of the active enzyme. Note that the name of a given enzyme is only shown in the sections of the table where sequences are known. The two lower lines illustrate residues common in gastric enzymes and common in all sequenced structures. 

Throughout the 373 positions of amino acid residues in the gastric zymogens, 175 are found with identical residues in the presently known structures. This number will probably decrease somewhat when more structures are determined. If we compare the gastric enzymes with the microbial enzymes represented by penicillo-pepsin, and Mucor miehei proteinase, 63 positions are identical. 

The aspartic acid residue 261 (215 in the pepsin numbering) is the site of esterification by diazoacetyl-norleucinemethyl ester or similar compounds. As might be expected for an active center residue, it is embedded in conservative segments from Ile-259 to Leu-267 where 6 identities are observed in 9 positions. Finally, in the COOH-terminal sequence from Gly-349 to Ala-370 eight residues are in identical positions. In this section Arg-354 and Arg-362 are common to all the gastric enzymes, while penicillopepsin has a lysine residue at position 354, and a serine residue at position 362. 

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