-
How many subunits does the H+, K+ - ATPase have and what are they?
2, catalytic alpha (larger) and glycosylated regulatory beta
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Which residue is responsible for H+, K+ ATPase loss of the enzyme bound H+ into the extracytoplasmic space?
LYS791
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Is the potassium binding region of H+, K+ - ATPase affected by LYS791?
No
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Extracystolic K+ binds to what residues on the H+, K+ - ATPase before being transferred into the parietal cell? GLU795 and GLU820
-
Dephosphorylation of the H+, K+ - ATPase occurs at what point in its operation?
Right before K+ release in the cytoplasm
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Phosphorylation of the H+, K+ - ATPase occurs at what point in its operations?
Right before the H+ is expelled into the cytoplasm
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H+, K+ - ATPase has how many transmembrane segments?
10
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The H+, K+ - ATPase has how many CYS residues?
28
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What H+, K+ - ATPase residue is most critical to binding PPIs?
CYS813
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Which residue of H+, K+ - ATPase is the inner CYS?
CYS882
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What type of PPIs can interact with CYS882 (inner)?
Those that are activated more slowly
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What type of bonding interaction do PPIs have with the H+, K+ - ATPase?
Irreversible Covalent Disulfide (between sulfurs on CYS and PPI)
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(True/False) PPIs have very potent long lasting effects.
True
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Are the disulfide bonds formed between the H+, K+ -ATPase and the PPI readily reversible?
No
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What is capable of regenerating the PPI inhibited pump?
GSH
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What limits GSH reactivation of the PPI inhibited pump?
Limited stores and PPIs that bind CYS822 (as CYS822 is deep and hidden from GSH)
-
What races are the Poor CYP2C19-metabolizing phenotypes are
prevalent in?
- Chinese (14.3%),
- Korean (14.0%)
- Japanese (21.3%)
- 3-5% of Caucasians and African Americans
-
The greatest risk of PPI toxicity due to CYP2C19 inhibition occurs with what drugs?
omeprazole and esomeprazole
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What PPI would you use in a CYP2C19 poor metabolizer to prevent toxic effects?
Rabeprazole
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Doses of PPIs should be decreased in what groups?
Severe Hepatic impairment and febrile elderly
-
What is achlorhydria?
Lack of gastric acid
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Some PPIs have DDIs that cause decreased absorption of the other drugs, what are these drugs?
- cephalosporin antibiotics (decreased
- absorption)
- ketoconazole (decreased tablet dissolution,leading to decreased absorption)
- indinavir (decreased tablet dissolution,leading to decreased absorption)
-
Some PPIs have DDIs that cause increased absorption of the other drugs, what are these drugs?
- clarithromycin (increased absorption)
- digoxin (increased absorption)
- salicylates (increased enteric-coated tabletdissolution, leading to an increase in gastric side effects)
- theophylline (increased absorption fromsustained release formulations)
- vitamin B12 (decreased absorption)
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