Lecture 9 & 10: UNIT 2 Metabolism Flashcards
Enzymes that catalyze xenobiotic biotransformation are often called
drug-metabolizing enzymes.
Xenobiotic biotransformation is the process
is a series of enzyme-catalyzed processes that alters the physiochemical properties of foreign chemicals (xenobiotics) from those that favour absorption across biological membranes (namely, lipophilicity) to those favouring elimination in urine or bile (namely, hydrophilicity)
Absent xenobiotic biotransformation, many of the drugs in use today would have an
unacceptably long duration of action
Xenobiotic biotransformation or drug metabolism is the process of
converting lipophilic (fat-soluble) chemicals, which are readily absorbed from the gastrointestinal tract and other sites, into hydrophilic (water-soluble) chemicals, which are readily excreted in urine or bile.
Four categories enzyme systems
- Hydrolysis (eg, carboxylesterase)
- Reduction (eg, carbonyl reductase)
- Oxidation (eg, cytochrome P450 [CYP])
- Conjugation (eg, Uridine 5’-diphospho-glucuronosyltransferase)
Individual xenobiotic-bio-transforming enzymes are located in
a single organelle, however, in such cases, the enzyme name generally refers to 2 or more enzymes, each with its own distinct subcellular location.
xenobiotic biotransformation is accomplished by
a limited number of enzymes with broad substrate specificities
Base on all the enzymes that perform biotransformation on xenobiotics, _____ ranks first.
CYP 450
The highest presence of CYP 450 can be found in the
liver’s SER, but the enzymes are in all tissues.
Cytochrome P450 (CYP 450) consists of how many gene families.
27 gene families.
The three main gene families important in xenobiotic metabolism
CYP1, CYP2, and CYP3.
Why is the CPY4 not best for xenobiotic metabolism
There also CYP4 but it works mostly of fat metabolism.
How many families are within CYP 450?
There is one subfamily, i.e., CYP1A, CYP3A, CYP4A,
How many subfamilies does CYP2 have?
CYP2 have five subfamilies A, B, C, D, and E.
CYP 450 can be further subdivided into genes that
code for single enzyme proteins, such as CYP1A1 and CYP1A2.
Subfamilies are denoted by capital
letters
CYP3A4 means the
4th gene to be sequenced in the CYP3A subfamilies
Proteins and genes are denoted
by Arabic numerals.
A compound derived from the parent drug via metabolic pathways in
Phase I and/or Phase II.
Metabolites are
the intermediate products of metabolic reactions catalyzed by various enzymes that naturally occur within cells.
How does metabolism works?
Substances that enter the body are usually fat loving and are not ideal for excretion. They will be reabsorbed in the kidney or from the GI after biliary excretion.
Metabolism (Biotransformation) makes the compounds more _____ compounds so they can be readily excreted.
polar
Results of Metabolism
- Parent molecule is converted into a more polar metabolite
- Molecular weight/size increased
- Facilitation of excretion from the body is increased
Consequences of Metabolism
- Biological half-life is decreased
- Duration of exposure is reduced
- Accumulation of compound in the body is avoided
- Biological activity may change
- Duration of biological activity may be affected
Enzymes are responsible for
the conversion of compounds in the body and xenobiotics as well.
Enzymes bind to compounds based on
structure and physiochemical properties
Xenobiotics are not exclusively metabolized by
a specific enzymes.
The organ responsible for the majority of xenobiotic transformation
is the liver.
What oragn transports the majority of foreign compounds to the liver?
GI tract
Why does the liver serve as a gateway to the rest of the body?
Because it converts endogenous compounds, it is ideal for converting xenobiotics.
First-Pass effect can be so extensive that
none of the parent compound reaches the circulatory system.
Enzymes that part take in biotransformation are usually found in:
- Smooth endoplasmic reticulum (SER) (Most are found here)
- Cytosol
- Mitochondria
Biotransformation is divided into how many phases?
Two phases
