What is glucuronide conjugate?

Glucuronide conjugate process is perhaps the major and most common route for Phase II metabolism to form water-soluble metabolites. Glucuronide conjugation involves the direct interaction of the drugs and xenobiotics (or its Phase I metabolite) with the cofactor UDP–glucuronic acid (UDPGA) as shown in Fig. 8.2.

Which drugs are metabolized by glucuronide conjugation?

Affected drugs

• Amitriptyline.
• Clomipramine.
• Clonazepam.
• Diazepam.
• Flunitrazepam.
• Lorazepam.
• Nitrazepam.
• Oxazepam.

Why are acyl Glucuronides toxic?

Acyl glucuronides (AGs) are reactive metabolites that have been linked to toxicity. Acyl glucuronidation is a common metabolic fate for acidic drugs and their metabolites and, because these metabolites are reactive, they have been linked to adverse drug reactions (ADRs) and drug withdrawals.

What type of reaction is Glucuronidation?

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 acetylation in drug metabolism?

Acetylation (or in IUPAC nomenclature ethanoylation) is an organic esterification reaction with acetic acid. Conversely, drugs such as isoniazid are acetylated within the liver during drug metabolism. A drug that depends on such metabolic transformations in order to act is termed a prodrug.

What is the purpose of glucuronidation?

Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination.

What are the four stages of drug metabolization?

Think of pharmacokinetics as a drug’s journey through the body, during which it passes through four different phases: absorption, distribution, metabolism, and excretion (ADME).

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 does a glucuronide do?

Glucuronidation, the conversion of chemical compounds to glucuronides, is a method that animals use to assist in the excretion of toxic substances, drugs or other substances that cannot be used as an energy source.

What is an acyl glucuronide?

Acyl glucuronidation is the major metabolic conjugation reaction of most carboxylic acid drugs in mammals. Specifically, the complex transacylation and glycation reactions with proteins have provoked much inconclusive debate over the safety of drugs metabolised to acyl glucuronides.

How do you increase glucuronidation?

Supporting Glucuronidation:

1. Citrus Fruits: limonene from the peels of oranges, lemons, limes, and grapefruit and believed to induce UGT activity.
2. Cruciferous vegetables.
3. Dandelion, rooibos, honeybush, and rosemary tea.
4. Astaxanthin found in algae, yeast, trout, krill, shrimp, and crayfish.

What is the sulfation pathway?

The sulfation and desulfation reactions modifying a variety of different substrates are commonly known as sulfation pathways. In humans, mutations in the genes encoding the sulfation pathway enzymes underlie a number of developmental aberrations, and in flies and worms, their loss-of-function is fatal.

When to use glucuronide to conjugate acetaminophen?

Levy et al. 78 demonstrated that 2- to 3-day-old term infants had a limited ability to conjugate acetaminophen with glucuronide, which is the major conjugation pathway in adults. However, this limitation in glucuronidation was compensated for by a well-developed sulfation pathway.

How is glucuronidation a reaction of conjugation?

Glucuronidation is a major and very frequent reaction of conjugation. It involves the transfer to the substrate of a molecule of glucuronic acid from the cofactor uridine-5′-diphospho-α-D-glucuronic acid (UDPGA).

How does glucuronidase work in morphine conjugates?

Figure 1. General mechanism for glucuronidation of morphine from UDP-Glucuronic acid. For this reason, when a patient ingests a controlled substance, either legitimately or illegally, glucuronide conjugates, such as Morphine-6-glucuronide will be present in the subject’s blood as well as urine.

How is beta glucuronidase used in hydrolysis?

The useful application of Beta-Glucuronidase in hydrolysis of glucuronides. Organic mechanism of glucuronide conjugate hydrolytic cleavage.