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Bio Transformation Bibek Singh Mahat RN07

Bio Transformation Bibek Singh Mahat RN07

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Published by Bibek Singh Mahat
1. Introduction
a) Xenobiotics
b) Chemical Reactions
c) Categorization of the Biotransformation reactions
2. Phase I Reactions
a) Oxidation
b) Reduction
c) Hydrolysis
d) Cytochrome P450 system
3. Phase II Reactions
a) Glucuronide conjugation
b) Sulfate conjugation
4. Biotransformation Sites
5. Modifiers of Biotransformation
a) Age
b) Genetic variability in biotransforming capability
c) Poor nutrition
d) Enzyme inhibition and enzyme induction
e) Dose level
6. References
1. Introduction
a) Xenobiotics
b) Chemical Reactions
c) Categorization of the Biotransformation reactions
2. Phase I Reactions
a) Oxidation
b) Reduction
c) Hydrolysis
d) Cytochrome P450 system
3. Phase II Reactions
a) Glucuronide conjugation
b) Sulfate conjugation
4. Biotransformation Sites
5. Modifiers of Biotransformation
a) Age
b) Genetic variability in biotransforming capability
c) Poor nutrition
d) Enzyme inhibition and enzyme induction
e) Dose level
6. References

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Categories:Types, Reviews, Book
Published by: Bibek Singh Mahat on May 02, 2011
Copyright:Attribution Non-commercial

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08/10/2012

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B
IOTRANSFORMATION
 
Page
 
1
 
of 
 
20.
 
Prepared
 
and
 
submitted
 
by:
 
Bibek
 
Singh
 
Mahat,
 
Roll
 
No.
 
07,
 
M.
 
Pharm.
 
(Industrial),
 
May
 
2010
 
BIOTRANSFORMATION
SUBMITTED FOR INTERNAL EVALUATION FORTHE DEGREE IN MASTER IN PHARMACYBYBIBEK SINGH MAHAT, M. PHARM STUDENT,2nd SEMESTER, BATCH OF 2009SUBMITTED TO:
Dr. Dharma Prasad Khanal
DEPARTMENT OF PHARMACYSCHOOL OF SCIENCEKATHMANDU UNIVERSITYDHULIKHEL, NEPAL
 
B
IOTRANSFORMATION
 
Page
 
2
 
of 
 
20.
 
Prepared
 
and
 
submitted
 
by:
 
Bibek
 
Singh
 
Mahat,
 
Roll
 
No.
 
07,
 
M.
 
Pharm.
 
(Industrial),
 
May
 
2010
 
TABLE
 
OF
 
CONTENTS:
 
1.
 
Introduction
a)
 
Xenobioticsb)
 
Chemical Reactionsc)
 
Categorization of the Biotransformation reactions 
2.
 
Phase I Reactions
a)
 
Oxidationb)
 
Reductionc)
 
Hydrolysisd)
 
Cytochrome P450 system
3.
 
Phase II Reactions
a)
 
Glucuronide conjugationb)
 
Sulfate conjugation
4.
 
Biotransformation Sites5.
 
Modifiers of Biotransformation
a)
 
Ageb)
 
Genetic variability in biotransforming capabilityc)
 
Poor nutritiond)
 
Enzyme inhibition and enzyme inductione)
 
Dose level
6.
 
References
 
B
IOTRANSFORMATION
 
Page
 
3
 
of 
 
20.
 
Prepared
 
and
 
submitted
 
by:
 
Bibek
 
Singh
 
Mahat,
 
Roll
 
No.
 
07,
 
M.
 
Pharm.
 
(Industrial),
 
May
 
2010
 
Introduction
 
Biotransformation is the process whereby a substance is changed from one chemical to another(transformed) by a chemical reaction within the body. Metabolism or metabolic transformationsare terms frequently used for the biotransformation process. However, metabolism is sometimesnot specific for the transformation process but may include other phases of toxico-kinetics.Biotransformation is vital to survival in that it transforms absorbed nutrients (food, oxygen, etc.)into substances required for normal body functions. For some pharmaceuticals, it is a metabolitethat is therapeutic and not the absorbed drug. For example, phenoxy-benzamine, a drug given torelieve hypertension, is biotransformed into a metabolite, which is the active agent.Biotransformation also serves as an important defense mechanism in those toxic xenobiotics andbody wastes are converted into less harmful substances and substances that can be excreted fromthe body.Toxicants that are lipophilic, non-polar, and of low molecular weight are readily absorbedthrough the cell membranes of the skin, gastrointestinal (GI) tract, and lungs. These samechemical and physical properties control the distribution of a chemical throughout the body andits penetration into tissue cells. Lipophilic toxicants are hard for the body to eliminate and canaccumulate to hazardous levels. However, most lipophilic toxicants can be transformed intohydrophilic metabolites that are less likely to pass through membranes of critical cells.Hydrophilic chemicals are easier for the body to eliminate than lipophilic substances.Biotransformation is thus a key body defense mechanism.Fortunately, the human body has a well-developed capacity to biotransform most xenobiotics aswell as body wastes. An example of a body waste that must be eliminated is hemoglobin, theoxygen-carrying iron-protein complex in red blood cells. Hemoglobin is released during thenormal destruction of red blood cells. Under normal conditions hemoglobin is initiallybiotransformed to bilirubin, one of a number of hemoglobin metabolites. Bilirubin is toxic to thebrain of newborns and, if present in high concentrations, may cause irreversible brain injury.Biotransformation of the lipophilic bilirubin molecule in the liver results in the production of water-soluble (hydrophilic) metabolites excreted into bile and eliminated via the feces. Thebiotransformation process is not perfect. When biotransformation results in metabolites of lowertoxicity, the process is known as detoxification. In many cases, however, the metabolites aremore toxic than the parent substance. This is known as bio-activation.Occasionally, biotransformation can produce an unusually reactive metabolite that may interactwith cellular macromolecules (e.g., DNA). This can lead to very serious health effects, forexample, cancer or birth defects. An example is the biotransformation of vinyl chloride to vinylchloride epoxide, which covalently binds to DNA and RNA, a step leading to cancer of the liver.

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