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Paracetamol poisoning can occur accidentally or as an attempt to die by suicide. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other hepatotoxic medications. [1] Liver damage results not from paracetamol itself, but from one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI). [6]
For example, CYP2E1 is the gene that encodes the enzyme CYP2E1—one of the enzymes involved in paracetamol (acetaminophen) metabolism. The CYP nomenclature is the official naming convention, although occasionally CYP450 or CYP 450 is used synonymously. These names should never be used as according to the nomenclature convention (as they denote ...
NAPQI, also known as NAPBQI or N-acetyl-p-benzoquinone imine, is a toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol (acetaminophen). [1] It is normally produced only in small amounts, and then almost immediately detoxified in the liver.
Cytochrome P450 enzymes metabolize approximately 60% of prescribed drugs, with CYP3A4 responsible for about half of this metabolism; [6] substrates include acetaminophen (paracetamol), codeine, ciclosporin (cyclosporin), diazepam, erythromycin, and chloroquine. [5] The enzyme also metabolizes some steroids and carcinogens. [7]
Paracetamol inhibits prostaglandin synthesis by reducing the active form of COX-1 and COX-2 enzymes. This occurs only when the concentration of arachidonic acid and peroxides is low. Under these conditions, COX-2 is the predominant form of cyclooxygenase, which explains the apparent COX-2 selectivity of paracetamol.
The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and paracetamol (acetaminophen). The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region.
In contrast, paracetamol (acetaminophen) is regarded as being safe and well tolerated during pregnancy, but Leffers et al. released a study in 2010, indicating that there may be associated male infertility in the unborn. [92] [93] Doses should be taken as prescribed, due to risk of liver toxicity with overdoses. [94]
In biochemistry, cytochrome P450 enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. [1] As of 2018 [update] , more than 300,000 distinct CYP proteins are known.