How does dealkylation work?

Asked by: Rey Bahringer
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In the first step, the enzyme removes a hydrogen atom from the carbon adjacent to the oxygen (Hydrogen atom transfer, HAT), to generate a neutral carbon radical. Hydroxyl recombination follows in the second step to form a hemiacetal intermediate.

What does n-Dealkylation do?

N-Dealkylation is a frequently encountered metabolic reaction. It is often responsible for the production of the major metabolite obtained from an N-alkyl containing drug.

Is n-Dealkylation oxidation?

N-Dealkylation, but not N-oxidation, is enhanced when NADH is present in addition to the NADPH-regenerating cofactors. 3. Some inhibitors, e.g. p-chloromercuribenzoate, inhibit N-dealkylation to a very much greater extent than they do N-oxidation.

What is a conjugation reaction?

These reactions involve covalent attachment of small hydrophilic endogenous molecule such as glucuronic acid, sulfate, or glycine to form water-soluble compounds, that are more hydrophilic. This is also known as a conjugation reaction. The final compounds have a larger molecular weight.

What are the two phases of drug metabolism?

Drug metabolism reactions comprise of two phases: Phase I (functionalization) reactions such as oxidation, hydrolysis; and Phase II (conjugation) reactions such as glucuronidation, sulphate conjugation. Oxidation reactions are the most common and vital.

Phase I Metabolism - Pharmacology Lect 7

33 related questions found

What is phase 1 metabolism?

Phase I metabolism consists of reduction, oxidation, or hydrolysis reactions. These reactions serve to convert lipophilic drugs into more polar molecules by adding or exposing a polar functional group such as -NH2 or -OH. ... These reactions include conjugation reactions, glucuronidation, acetylation, and sulfation.

What causes slow drug metabolism?

Underlying health conditions can also influence your drug metabolic rate. Some conditions at greater risk of this are chronic liver disorders, kidney dysfunction, or advanced heart failure.

What are the process of conjugation?

Conjugation is the process by which one bacterium transfers genetic material to another through direct contact. During conjugation, one bacterium serves as the donor of the genetic material, and the other serves as the recipient. The donor bacterium carries a DNA sequence called the fertility factor, or F-factor.

What is the difference between Phase 1 and Phase 2 metabolism?

The key difference between phase I and phase II metabolism is that the phase I metabolism converts a parent drug to polar active metabolites while phase II metabolism converts a parent drug to polar inactive metabolites. Metabolism (drug metabolism) is the anabolic and catabolic breakdown of drugs by living organisms.

What is the significance of conjugation?

3 Conjugation. Conjugation is an important process for genetic exchange between bacteria. The process needs mating of donor cell and recipient cell, and involves a cis-acting nick site (oriT) and the trans-acting functions given by a transfer protein.

Is demethylation an oxidation?

In biochemical systems, the process of demethylation is catalyzed by demethylases. These enzymes oxidize N-methyl groups, which occur in histones and some forms of DNA: ... One such oxidative enzyme family is the cytochrome P450.

What enzymes are involved in N oxidation and N-Dealkylation?

While both secondary and tertiary alkylamino moieties (open chain aliphatic or heterocyclic) are metabolized by CYP450 isozymes oxidative N-dealkylation, only tertiary alkylamino moieties are subject to metabolic N-oxidation by Flavin-containing monooxyge- nase (FMO) to give N-oxide products.

What is Glucuronidation reaction?

Glucuronidation is a conjugation reaction whereby glucuronic acid, derived from cofactor UDP-glucuronic acid, is covalently linked to a substrate containing a nucleophilic functional group. The resultant metabolite, called a glucuronide, is usually excreted in bile and urine.

What is oxidative N-Dealkylation?

N-oxidation are generally believed to involve transfer of an electron (SET) from the lone pair on the nitrogen to the perferryl species to generate compound II followed by oxygen recombination to give the N-oxide product. N-dealkylation is a major metabolism pathway for many amine drugs.

What happens when metabolic enzymes are inhibited?

The substrate can still bind to the enzyme, but the inhibitor changes the shape of the enzyme so it is no longer in optimal position to catalyze the reaction. Figure: Allosteric inhibitors and activators: Allosteric inhibitors modify the active site of the enzyme so that substrate binding is reduced or prevented.

What is aromatic hydroxylation?

Aromatic hydroxylation is an important metabolic process as evidenced by the reactions of heme-containing P450s, flavin monooxygenases, pterin-dependent nonheme monooxygenases, nonheme mononuclear iron dioxygenases, and diiron hydroxylases (1–4).

What is Phase 1 and 2 of drug metabolism?

Phase I reactions of drug metabolism involve oxidation, reduction, or hydrolysis of the parent drug, resulting in its conversion to a more polar molecule. Phase II reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine.

Where does Phase 1 and 2 metabolism occur?

The liver is the primary site for metabolism. Liver contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways: Phase I (functionalization reactions) and Phase II (biosynthetic reactions) metabolism.

Do all drugs go through Phase 1 and Phase 2 metabolism?

This is called conjugation and the product is called a conjugate. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1 metabolism followed by phase 2 metabolism.

What are the types of conjugation?

Perfect tense conjugations:
  • Present perfect simple: He has spoken about it.
  • Present perfect progressive: He has been speaking about it.
  • Past perfect progressive: He had been speaking about it.
  • Past perfect simple: He had spoken about it.

What is conjugation and why is it important?

Conjugation is a mechanism whereby a bacterium can transfer genetic material to an adjacent bacterium. The genetic transfer requires contact between the two bacteria . This contact is mediated by the bacterial appendage called a pilus. Conjugation allows bacteria to increase their genetic diversity.

What is conjugation and its types?

Bacterial conjugation is a sexual mode of genetic transfer in the sense that chromosomal material from two sexually distinct cell types is brought together in a defined and programmed process.

How concentrated is the drug after 2 hours of administration?

1 hour after the drug administration, 6.25 mg of the drug remains in the body. 2 hours after the drug administration, 0.39 mg of the drug remains in the body.

How do you know if you are a poor metabolizer?

Poor Metabolizer: Medication is broken down very slowly. May experience side effects at standard doses. Intermediate Metabolizer: Slow rate of metabolism. May have too much medication at standard doses, potentially causing side effects.

What factors affect metabolism of a drug?

Various physiological and pathological factors can also affect drug metabolism. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences.