5-Chemistry-Biochemistry-Drug-Metabolism

drug metabolism

Drug breakdown by oxidation {drug metabolism} is mainly in liver.

adduct

Compounds can have an added group {adduct}.

drug-drug interaction

Drug can inhibit or induce another drug {drug-drug interaction}.

flavoprotein

Proteins {flavoprotein} can bind FAD or FMN.

glutathione

Molecules {glutathione} (GSH) can participate in phase II conjugations.

hepatic first-pass elimination

Phase I oxidations, Phase II conjugations, and transport into bile reduce drug in hepatic blood {hepatic first-pass elimination} (HFPE).

iron-oxene

Iron compounds {iron-oxene} {iron-oxenoid} can contain free oxygen atoms.

metabolite

Drug metabolism makes products {metabolite}.

metabolite intermediate complexation

Nitrosoalkanes irreversibly bind to reduced heme intermediates of CYP450 enzymes {metabolite intermediate complexation}.

mutagenicity

Compounds or forces can mutate genes {mutagenicity}.

regioselectivity

Metabolism percentage {regioselectivity} categorizes sites as major, minor, or unobservable. Rate constant differences among sites cause metabolic-site regioselectivity.

selectivity of drug

Drugs can affect targets {selectivity, drug} and other sites.

5-Chemistry-Biochemistry-Drug-Metabolism-Binding

agonist molecule

Substrates {agonist} can bind to receptors and cause biologic response.

antagonist molecule

Substrates {antagonist, chemistry} can bind to receptor but cause no biologic response.

5-Chemistry-Biochemistry-Drug-Metabolism-Chemical Reaction

acetylation

Hydrogen atoms can bind to carbon atoms {acetylation}.

amino acid conjugation

Amino acids can bind to carboxylic-acid groups {amino acid conjugation}, on anti-inflammatory, hypolipidaemic, diuretic, and analgesic drugs.

bioactivation

Enzymes can change drugs to make them toxic {bioactivation}.

biotransformation

Drug metabolism has oxidations and reductions {biotransformation}.

charge-transfer coupling

Two charges can exchange {charge-transfer coupling} in reactions.

conjugation of molecule

Molecules can attach small molecule {conjugation, molecule}.

cyclization

Processes can make rings {cyclization}.

glucuronic acid conjugation

Glucuronic acid allows glucuronide formation {glucuronic acid conjugation}.

glutathione conjugation

Molecules can conjugate with glutathione {glutathione conjugation} to form mercapturic acid.

hydrogen bond acceptor

Atoms {hydrogen bond acceptor} (HBA) can add hydrogen atom.

hydrogen bond donor

Atoms {hydrogen bond donor} (HBD) can release hydrogen atom.

hydrogen transfer

Hydrogen atoms can abstract {hydrogen transfer}.

hydroxylation

Hydrogen atoms can bind to oxygen atom {hydroxylation}.

induced fit

Enzymes can change conformation to allow substrate binding {induced fit}.

intrinsic activity

Drugs can form complexes with receptors and then cause chemical or conformational changes {intrinsic activity, drug}.

Phase I enzyme reaction

Drug metabolism has oxidation or reduction {Phase I enzyme reaction}.

Phase II enzyme reaction

Drug metabolism has conjugation with small molecules {Phase II enzyme reaction}.

proton abstraction

Hydrogen atoms removed from molecules {proton abstraction} can make water.

sulfate conjugation

After ATP activates sulfate, sulfotransferase makes sulfate esters {sulfate conjugation}.

5-Chemistry-Biochemistry-Drug-Metabolism-Energy

guanidine diphosphate

nucleophosphate energy compound {guanidine diphosphate} (GDP).

uridine diphosphate

Energy molecules {uridine diphosphate} (UDP) can participate in phase II reactions.

5-Chemistry-Biochemistry-Drug-Metabolism-Enzyme

adenylate cyclase

Enzymes {adenylate cyclase} {adenylcyclase} can alter cAMP.

carboxylesterase

Enzymes {carboxylesterase} can catalyze phase I reactions.

cytochrome P-450

Enzymes {cytochrome P-450} catalyze phase I reactions 3A4, 2D6, 2C9, 1A2, and 2E1.

epoxide hydratase

Enzymes {epoxide hydratase} {epoxide hydrolase} can oxidize olefins and aromatics to make epoxide or oxirane metabolites. It can produce carcinogens.

glucuronyl-transferase

Enzymes {glucuronyl-transferase} can catalyze phase II reactions, adding glucuronide to drugs.

glutathione-S-transferase

Enzymes {glutathione-S-transferase}, in liver-cell cytoplasm, can catalyze phase II reactions to conjugate compounds to glutathione.

microsomal flavoprotein mono-oxygenase

Enzymes {microsomal flavoprotein mono-oxygenase} can oxidize nitrogen or sulfur organics.

microsomal hydroxylase

Enzymes {microsomal hydroxylase} can catabolize many compounds, mostly by oxidation, in endoplasmic reticulum.

mixed-function oxidase

Enzymes {mixed-function oxidase} (MFO) can catabolize many compounds, mostly by oxidation, in endoplasmic reticulum.

phospholipase A2

Enzymes {phospholipase A2} can catabolize lipids.

phospholipase C

Enzymes {phospholipase C} can catabolize lipids.

protein kinase

Enzymes {protein kinase} can catabolize proteins.

uridine diphosphoglucose

Enzymes {uridine diphosphoglucose transferase} {uridine-diphosphate-glucuronosyl-transferase} (UDP-GT) (UGT) can catalyze phase II reactions, adding glucuronide to drugs.

5-Chemistry-Biochemistry-Drug-Metabolism-Inhibition

drug inhibition

Chemicals can inhibit drugs {drug inhibition}. Inhibitor has binding constant.

allosteric non-competitive inhibition

Inhibitor can bind to non-active site {allosteric non-competitive inhibition}.

entry inhibitor

Drugs {entry inhibitor} can prevent viruses from entering cells.

integrase inhibitor

Drugs {integrase inhibitor} can prevent virus DNA from inserting into host DNA.

maturation inhibitor

Drugs {maturation inhibitor} can block gag-protein protease receptor, so gag protein is not split, and HIV virus coat is not made. PA-457 comes from betulinic acid from Taiwan herb, plane trees, and birch trees.

mechanism-based inhibition

Metabolized compounds can bind to enzymes {mechanism-based inhibition}.

protease inhibitor

Drugs {protease inhibitor} can inhibit protease enzymes.

5-Chemistry-Biochemistry-Drug-Metabolism-Orbital

highest occupied molecular orbital

Most-reactive electron {highest occupied molecular orbital} (HOMO) can be in electron-rich nucleophilic molecules.

lowest unoccupied molecular orbital

Most-reactive electron {lowest unoccupied molecular orbital} (LUMO) can be in electron-poor electrophilic molecules.

5-Chemistry-Biochemistry-Drug-Metabolism-Rate

absolute metabolism rate

Total metabolism has rate {absolute metabolism rate}.

enzyme kinetics

Reaction rate typically depends on concentration and temperature {enzyme kinetics}.

lability

Metabolism rate at site has estimated ease {lability}.

Michaelis-Menten constant

Enzymes have binding constants {Michaelis-Menten constant} (Km).

5-Chemistry-Biochemistry-Drug-Metabolism-Site

labile site

Sites {labile site} can have high metabolism rate and low activation energy.

moderate site

Sites {moderate site} can have intermediate metabolism rate and activation energy.

stable site

Sites {stable site} can have low metabolism rate and high activation energy.

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Date Modified: 2022.0225