1. Restoration of acid secretion following treatment with proton pump inhibitors 
Jai Moo Shin, George Sachs 
Gastroenterology 
Volume 123, Issue 5, Pages (November 2002)
DOI: /gast
Copyright © 2002 American Gastroenterological Association Terms and Conditions

2. Fig. 1
The structure of the PPIs omeprazole, lansoprazole, pantoprazole, and rabeprazole.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Quantitative analysis of the gastric H+,K+-ATPase in resting membranes. The quantity of H+,K+-ATPase was determined by Western blot analysis with antibody Ab12.18 and comparing the intensity with the given amounts of hog gastric H+,K+-ATPase. The typical example in this figure shows an average content of 184 ng of the H+,K+-ATPase per microgram of the resting membrane protein.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Comparison of the time-dependent reversal of (♦) omeprazole-, (□) S-omeprazole–, (▵) R-omeprazole–, and (×) pantoprazole-inhibited gastric acid pump of resting membranes using incubation with DTT as reversal agent. An aliquot of the PPI-inhibited enzyme in vivo was incubated with 10 mmol/L DTT (37°C) and its activity assayed at different times after addition of DTT. Activity was calculated as the percent of recovery of the control ATPase specific activity of each PPI inhibited.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Comparison of the time-dependent reversal of (•) lansoprazole-, ( ̂) rabeprazole-, and (×) pantoprazole-inhibited gastric acid pump in resting membranes using DTT as reversal agent. See the legend to Figure 3 for methods.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Comparison of reversibility of (♦) omeprazole-, (□) S-omeprazole–, (▵) R-omeprazole–, (•) lansoprazole-, ( ̂) rabeprazole-, and (×) pantoprazole-inhibited gastric acid pump of stimulated membranes using DTT as reversal agent. See the legend to Figure 3 for methods.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

7. Fig. 6
Comparison of reversal of (♦) omeprazole- and (×) pantoprazole-inhibited gastric acid pump using glutathione as reversal agent. (A) An aliquot of the PPI-inhibited enzyme in vivo of freeze-thawed resting membranes was incubated with 10 mmol/L glutathione at 37°C for 45 minutes and its activity assessed. (B) An aliquot of the PPI-inhibited enzyme in stimulated membranes was incubated with 10 mmol/L glutathione at 37°C for 60 minutes and its activity expressed as previously described.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

8. Fig. 7
The inhibitory mechanism of the PPIs. This mechanism is based on that of omeprazole as described by Gedda et al.7 The pyridine ring is protonated (first arrow) and accumulated in the secretory canaliculus, followed by intramolecular acid–catalyzed transfer of the proton to the benzimidazole nitrogen, which enables the intramolecular rearrangement by increasing the reactivity of the 2C with the pyridine N to form first the sulfhydryl reactive sulfenic acid (second arrow) and then the sulfenamide (third arrow). Either of the latter 2 compounds can react with cysteines on the enzyme surface (bottom structure). The table shows the substituents on the core structure for the different PPIs.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions

9. Fig. 8
The enzyme structure surrounding the PPI-reactive cysteines. A 3-dimensional model of the membrane domain of the H+,K+-ATPase showing the positions of cysteine 321, 813, 822, and 892. The structure represented here is derived from the E1 conformation of the sarcoplasmic reticulum ATPase at 2.8-Å resolution where the amino acids of the H+,K+-ATPase have been substituted at equivalent positions. The location of the cysteine at position 822 is deeper within the membrane domain compared with the other cysteines and also M8 is split to show the position of this cysteine. The transmembrane helices for M4, 5, 6, and 8 are shown as cylinders overlaying the peptide backbone to illustrate the vestibule surrounding cysteine 813 at the end of the 5–6 exoplasmic loop.
Gastroenterology  , DOI: ( /gast )
Copyright © 2002 American Gastroenterological Association Terms and Conditions