Study sets, textbooks, questions
Upgrade to remove ads
Conjugation of Drugs and Metabolites (Exam 2)
Terms in this set (36)
What are the principles of phase II reactions? (5)
1. Uses endogenous substrates and the xenobiotic or phase I metabolite of the xenobiotic.
2. Phase I adds, makes, or exposes reactive functional groups on xenobiotics in order for phase II reactions to occur.
3. Phase II reactions covalently link an endogenous substrate with the xenobiotic or phase I metabolite of the xenobiotic.
4. Reactive groups include -OH, -SH, -NH2, and -COOH
5. Since Phase II reactions are biosynthetic, the reactions require energy.
What do phase II reactions do?
Utilizes reactive groups on xenobiotics to produce biosynthetic reactions
What are the results of phase II reactions?
1. Conjugated compounds tend to be more water soluble.
2. Conjugated compounds have a larger molecular weight than the parent compound.
3. Conjugated xenobiotics usually have increased ionization at physiologic pH of serum (7.4)
4. Enhanced drug elimination from cellular compartments, as well as from the body.
What are the six common types of phase II reactions?
3. Glutathione conjugation
5. Amino acid conjugation
Which reaction is the most important for exogenous and endogenous compounds?
Glucuronidation is quantitatively and qualitatively, the most important conjugation pathways for exogenous and endogenous compounds.
T/F Glucuronidation occurs in only specific species
False, it has widespread species occurrence
What is the high energy intermediate for glucuronidation?
UDP-glucuronic acid (uridine-diphospho-glucuronic acid)
What is the primary binding site for glucuronidation?
Liver is quantitatively most important, but activity occurs in most tissues.
What is the enzyme used in glucuronidation?
____________ ___________ of the parent compound or phase I product is of primary importance in the route of elimination.
Increased molecule size means an increased probability of glucuronidative molecule elimination via bile.
What is enterohepatic circulation?
The process whereby a drug or a metastable metabolite thereof in the liver is secreted into the bile, stored in the gall bladder, and subsequently released into the small intestine, where the drug can be reabsorbed back into circulation and subsequently returned to the liver.
Which reaction is the most important for hydroxyl groups?
What is the high energy intermediate for sulfation?
What is the enzyme used in sulfation?
What are the primary binding sites for sulfation? (4)
Liver, kidney, intestinal tract, and lungs.
Which reaction is the beginning step in the formation of N-acetylcysteine (mercapturic acid)?
What is the high energy intermediate for glutathione conjugation?
A tripeptide made up of glycine, glutamic acid and cysteine.
T/F Glutathione conjugation is VERY important in binding to reactive P-450 products before they can react with essential components of the cell.
What are the primary binding sites for glutathione conjugation? (5)
Highest concentrations are found in the testes, liver, intestine, kidney, and adrenal glands.
What enzyme is used in glutathione conjugation?
Which reaction is the major route of conjugation of aryl-amines in most species?
What is the high energy intermediate for acetylation?
What enzyme is used for acetylation?
Acetyl CoA: N-acetyl transferases
Acetylation makes the compound more _________ ___________ compared to other pathways which make compounds more ________ ___________.
T/F Dogs and related species are deficient in acetylation capability.
Polymorphisms of acetylation have been reported in what species? (4)
Humans, mice, rabbits, and squirrel monkeys.
What is an example of acetylation polymorphism in humans?
South-East Asians are considered slow-acetylators (a lower capacity for acetylation). This can mean tissue or DNA damage from medications that use the acetylation pathway.
What are the primary binding sites for acetylation?
Reaction occurs in many tissues via several different acetyl transferases.
Where does acetylation occur?
Which reaction is important for xenobiotics that contain carboxylic acid groups?
Amino acid conjugation
What are the two steps in amino acid conjugation?
1. Using ATP-dependent acid:CoA ligase which causes activation of the acid to a thioester derivative of CoA
2. CoA thioester transfers its acyl moiety to the amino group of the acceptor amino acid via N-acyltransferase
Understand that CoA thioester and N-acyltransferase are the same thing
What are the primary binding sites for amino acid conjugation?
The cytoplasm of several tissues, but can also be found in the mitochondrial matrix of liver and kidney.
Which reaction is important for common biochemical reactions for the metabolism of endogenous compounds?
What is the high energy intermediate for methylation?
What are the primary binding sites for methylation?
Can be found throughout the body, but the highest concentration is in the liver and kidney.
What enzyme is used in methylation?
Sets found in the same folder
Induction and Inhibition of Metabolic Pa…
Variability in Xenobiotic Transformation…
Interactions in Xenobiotic Transformatio…
Other sets by this creator
Allergic Pathophysiology and Treatment