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Biotransformation
XENOBIOTICS AND DETOXIFICATION
Questions:
1. Detoxication of xenoiotics! a"ri# $%%1
$. Detoxication & con'u(ation)a"ri# $%%1
*. C&toc+rome , -%)a"ri# $%%-
-. /o0 are Xenoiotics etoxie & con'u(ation2 ,on No3 $%11
. Detoxication reactions. ,on 4a& $%1-
5. /o0 o t+e fo##o0in( Xenoiotics uner(o iotransformation2 ,on
4a&
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a. 4et+ano#
. ,icric aci
1. Detoxication refers to the process whereby the noxious
substances in human body
are rendered innocuous and water soluble for elimination. The
term detoxication is
replaced by biotransformation or metabolism of xenobiotics.2.
Biotransformation is transformation of one chemical to other
within the body by a
chemical reaction within the body.
3. Xenoiotics are compounds, which may be accidentally
ingested as drugs, or those
produced in vivo by bacterial metabolism. Eg
a. !ccidental ingestants preservatives, food additive, and
adulterants.
b. "rugs for therapeutic purposes eg. acetaminophen ta#en in
toxic dose gets
converted to a more toxic metabolite.
c. $n vivo
i. %ilrubin, and steroids from metabolism
ii. $n the large intestine by the bacteria which enter the
circulation. These
include indole from tryptophan, cadaverine from lysine,
tyraminef romtyrosine,p henolf rom phenylalanin
-. Site of etoxicationa. The detoxication reactions are carried
out mainly in the liver which is e&uipped
with the en'yme machinery.b. (idney and other organs may
sometimes be involved.c. The products formed by detoxication are
mostly excreted by the #idneys, less
fre&uently excreted via feces or expired air.
). 4ec+anism of etoxication $t is divided into two phases. *ne
or both phases may
be involved in detoxication.
a. +hase 1 the reactions are oxidation, reduction and
hydrolysis.
b. +hase 2 The reactions are conugation with groups li#e
glucuronic acid, amino
acid, lutathione, sul fate, acetate, and methyl groups.-.
Oxiation: !lcohols, aldehydes, amines, etc undergo oxidation.
c. ethanol /0 ormic acid
d. Ethanol /0 !cetic acid
e. %en'aldehyde /0 %en'oic acid
f. !liphatic amine /0 !liphatic acid
g. !niline /0 p!mino phenol.
h. ulphur /0 ulfuric acid
i. "rugs ebromamate /0 4ydroxymepbrobamate
2. 6euction: exam"#es: +icric acid is reduced picramic acid.
5hloral is reduced to
Trichloro ethanol.
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3. /&ro#&sis 4ydrolysis of esters, glycoside, amide are
examples. !spirin, atropine,
procaine are examples of detoxication by hydrolysis.
7. Con'u(ation:
a. 5onugation is the process in which a foreign compound
combines with a
substance produced in the body.
b. !t least 8 di9erent conugating agents have been identied in
the body
:lcuronic acid, glycine, 5ysteine, glutamine, methyl groups,
sulfate, acetic acid,
and thiosulfatesc. 5onugation with glucuronic acid is the most
common.The active form of
glucuronic acid is ;"+glucuronic acid produced in the uronic
acid pathway. The
microsomal en'ymes ;"+ glucuronyl transferase participate in
glucurnide
formation. Eg. %ilirubin *2 > D!"+4 > 4> F *4 > 42*
> D!"+>
7. !lmost all common drugs are metaboli'ed by the +7)6 system.
There are about 1)6
isoforms of the +7)6 en'ymes.They are inducible en'ymes.
+henobarbital causes
increased activity of +7)6.). The +7)6 en'ymes are seen in many
tissues, including adrenal glands, where they are
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