What enzyme breaks down paracetamol?

At therapeutic doses, paracetamol is predominantly metabolized by hepatic sulfation and glucuronidation, with less than 5%–10% being metabolized by the hepatic CYP system (predominantly CYP2E1 and CYP3A4) to N-acetyl-p-benzoquinoneimine (NAPQI), a highly reactive intermediate metabolite responsible for paracetamol- …

How does the liver metabolise paracetamol?

It is metabolized in the liver, predominantly by glucuronidation and sulphation to non-toxic conjugates, but a small amount is also oxidised via the cytochrome P450 enzyme system to form the highly toxic metabolite, N-acetyl-p-benzo-quinone imine (NAPQI).

What does a glucuronide do?

The human body uses glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body through urine or feces (via bile from the liver). Hormones are glucuronidated to allow for easier transport around the body.

What is the main pathway of paracetamol metabolism?

Glucuronidation is the main pathway of acetaminophen metabolism, followed by sulfation and a minor contribution from the oxidation route.

What is the antidote for paracetamol?

Intravenous acetylcysteine is the antidote to treat paracetamol overdose and is virtually 100% effective in preventing liver damage when given within 8 hours of the overdose.

Does paracetamol undergo first pass metabolism?

Paracetamol (acetaminophen) is a very common antipyretic and analgesic agent. It is well absorbed after oral administration, with bioavailability of 70–90% attributable to first pass metabolism [17,18,19].

Why is glucuronidation important?

Glucuronidation is a major mechanism for the formation of water-soluble substrates from xenobiotics, leading to their elimination from the body in bile or urine. Many xenobiotics, including drugs from almost all classes of therapeutic agents, are glucuronidated directly.

How is glucuronide excreted?

MPAG is excreted via bile into the gut where it exhibits a significant entero-hepatic recirculation, with a concomitant second peak in plasma mycophenolic acid concentration 6–12h after dosing.

What is paracetamol metabolism?

Paracetamol is metabolized primarily in the liver (Figure 1) by enzymes of phase I and II. Phase I reaction for paracetamol may occur by oxidation, reduction, and hydrolysis: It results in polar metabolites of the original chemicals and leads either to activation or inactivation of the drug.

How is paracetamol toxicity treated?

Acetylcysteine IV (N-acetylcysteine, Parvolex®, NAC) is the treatment of choice. It has near 100% efficacy in preventing paracetamol-induced hepatotoxicity if given within the first 8 hours from ingestion of overdose. It may also be effective up to and possibly beyond 24 hours.

How is glucuronosyltransferase related to infant jaundice?

Neonatal jaundice is common and transient in most normal infants. In the majority it is related to the immaturity of glucuronosyltransferase or to breastfeeding. 1 Conjugated hyperbilirubinemia, in contrast, is always significant and due to one of several underlying disorders.

Where does glucuronosyltransferase 1 add the fourth sugar?

Glucuronosyltransferase 1 (b3gat3) adds the fourth sugar to the tetrasaccharide linker and is the final enzyme before the divergence to HSPG- and CSPG-specific synthesis pathways ( Fig. 1 ).

How is glucuronidation catalyzed by the liver and extrahepatic tissues?

Glucuronidation, catalyzed by a family of uridine 5′-diphospho UDP-glucuronosyl transferases, is part of the metabolic clearance mechanism for steroid hormones by the liver and extrahepatic tissues.98-102 There are 18 known UDP-glucuronosyl transferases that have been divided into three subfamilies: UGT1A, UGT2A, and UGT2B.

Which is the preferred reaction of glucuronidation?

In general, glucuronidation is the preferred reaction in humans. An important pathway of O-glucuronidation is the formation of acyl-glucuronides. Substrates are anti-inflammatory arylacetic acids and aliphatic acids such as valproic acid ( 10 ).