Biology Oxidation 1

7/21/2019 Biology Oxidation 1

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BIOLOGIC OXIDATIONBIOLOGIC OXIDATION


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ENERGI(ATP)


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Source of ATP :

1. Glycolysis.2. Krebs Cycle.

3. Oxidative Phoshorylatio!.

Ox-red reactions

O2accept single electron


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Oxidation-reduction potential

" Oxidatio! : the re#oval of electro!s

" $eductio! : the %ai! of electro!s

" $edox ote!tial &'()* : the free e!er%y cha!%e

is roortio!ate to the te!de!cy of reacta!tsto do!ate or accet electro!s

" $edox ote!tial of a syste# &'o* is co#ared+ith the ote!tial of the hidro%e! electrode

" ,iolo%ic syste#s'()exressed at P- a!d electrode ote!tial of - : / (02 volts


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System EO volts

H+

/H2NAD+/ NADHLipoate ox / redAcetoacetate/ ! "#ydroxy$utyrate

%yruvate/ lactateOxaloacetate/ malate&umarate/ succcinate'ytoc#rome b &e!+/&e2+

($i)uinone ox/red'ytocrome c

* &e!+/&e2+

'ytocrome a &e!+/&e2+

Oxyen/ ,ater

-.2-.!2-.20-.21-.*0-.*1+.!+.+.*+.22+.20

+.2


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En3ymes in ox-red

" Called oxidoreductases

" classified i!to %rous:

oxidases dehydro%e!ases

hydroeroxidases

oxy%e!ases


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Oxidases

" Catalyi!% the re#oval hydro%e! a!d usi!%oxy%e! as a accetorfor# +ater &-2O* orhydro%e! eroxide&-2O2*

" So#e oxidases co!tai! coer a!d others

are flavorotei!s" Cytochro#e oxidase & cyt.a.a3* :

he#e rotei! co!tai! Cu

ter#i!al co#o!e!t of resiratory chai!co!tai! t+o #olecules of he#e asrosthetic %rou a!d Cu


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" 4lavorotei! e!y#s co!tai! 456 or 4A7 asrosthetic %rous

" 456 a!d 4A7 are for#ed i! body fro# riboflavi!

" They are ti%htly bou!d to their aoe!y#es

but !otcovale!tly

" 'xa#els: 8a#i!o acid oxidase &i! 9id!ey*0

xa!thi!e oxidase &i! i!testi!al0 9id!ey0 liver*0

aldehyde oxidase &i! liver* a!d %lucose

oxidase &i! fu!%us*

Oxidases


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AH2

A H2O

1

/2 O2

O45DASE

O2

H2O2

AH2

A

O45DASE

(Red)

(Ox)

Oxidation o6 a meta$olite cataly3ed $y an oxidase 7A8

6ormin H2O9 7:8 6ormin H2O2

A B


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De#ydroenases

" Ca! !ot use oxy%e! as a hydro%e! accetor

" Perfor#i!% t+o #ai! fu!ctio!s:

1. tra!sfer hydro%e! i! a couled oxidatio!reductio! reactio!

secific for their substrates0 but utilieco##o! coe!y#es

useful i! e!abli!% oxidative rocess tooccur i! the abse!ce of oxy%e!

2. co#o!e!ts i! resiratory chai!tra!sfer electro! fro# substrate to

oxy%e!


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7ehydro%e!ases li!9 6A7

" si!% 6A7;or 6A7P;as a coe!y#e

" These coe!y#e are for#ed i! body fro#

!iaci!

freely a!d reversibly dissociate fro# their

aoe!y#es 6A7 li!9ed 7ase: oxidative ath+ays of

#etabolis# &%lycolysis0 9reb)s cycle0

resiratory chai!*

6A7P li!9ed 7ase: characteristically i!

reductive sy!thesis &fatty acid sy!thesis0

steroid sy!thesis a!d P5Pshu!t*


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7ehydro%e!ases li!9 riboflavi!

" si!% 456 a!d 4A7 as a coe!y#e

#ore ti%htly bou!d to their aoe!y#es

#ost of the# are co!cer!ed +ith electro!

tra!sort i! < to res chai!

6A7- 7asecarrier of electro!sbet+ee! 6A7- a!d co#o!e!ts of hi%her

redox ote!tial

succi!ate 7ase0 acyl CoA 7ase0 %lycerol3 P 7asetra!sfer electro!s directly fro#substrate to res. chai!


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Cytochro#es as dehydro%e!ase

" Classified as dehydro%e!ases0 excet for

cytochro#e oxidase

as carriers of electro!s fro# flavorotei!s to

cytochro#e oxidase i! the res chai!

exa#els: cyt b0 c10 c0 a0 a3 &res chai!* a!d

cyt P =(0 b=&e!dolas#ic reticulu#*


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AH2

A

Carrier

(Red)

(Ox)

Oxidation o6 a meta$olite cataly3ed $y coupled

de#ydroenases

(Ox)

Carrier-H2(Red)

B

BH2(Red)

(Ox)

DEH;D


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Hydroperoxidases

" si!% hydro%e! eroxide or a! or%a!ic

eroxide as substrate

" T+o tye : eroxidase

catalase" Protecti!% a%ai!st har#ful eroxides

" Peroxides %e!erate free radicals

disrut #e#bra!es a!d cause ca!cer a!datherosclerosis.


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" Peroxidases

$educi!% eroxides usi!% various electro!

accetors &ascorbate0 >ui!o!es0 cyt c*:

-2O2; A-22-2O ; A

4ou!di!% i! #il90 leu9ocytes0 latelets0

erythrocytes a!d other tissues i!volved i!eicosa!oid #etabolis#

Glutathio!e eroxidase0 co!tai!i!% sele!iu#

destructio! of -2O2a!d liid

hydroeroxidasesrotecti!% #e#bra!eliids a!d -b


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" Catalase

si!% hydro%e! eroxide as electro! do!or a!delectro! accetor:

2 -2O22-2O ; O2

?! additio! to ossessi!% eroxidase activity0 it

is able to use o!e of -2O2 as a substrate

&electro! do!or* a!d a!other of -2O2 as a!

oxida!t &electro! accetor*

4ou!di!% i! blood0 bo!e #arro+0 #ucous#e#bra!es0 9id!ey a!d liver


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Oxyenases

" Catalyi!% the direct tra!sfer a!d

i!cororatio! of oxy%e! i!to a substrate" 7ivided i!to t+o sub%rous:

1. 7ioxy%e!ases < oxy%e! tra!sferase

?!cororati!% both ato#s of oxy%e! i!tosubstrate: A ; O2AO2

2. 5o!ooxy%e!ases

5ixed fu!ctio! oxidases a!d

hydroxylasesi!cororate o!ly 1 ato#

of oxy%e! i!to substrate0 the other oxy%e!

is reduced to +ater


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MONOOXYGENASES Need an additional electron donor /

cosubstrate ( !"A-# $ O2$ #2A-O# $ #2O $

%&toc'roes )*+, are onoox&genases (ascosubstrate ! iportant or detoxiicationo an& drugs and or '&drox&lation osteroids

NA.# and NA.)# donate reducingeui0alents or t'e reduction o c&t )*+,


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%&toc'roe ) *+, 1niue ail& o 'ee proteins present inbacteria ungi insects plants is'aals and priates

Monoox&genase Substrates or t'is en3&e s&ste include

4 Endogenous s&nt'esi3ed copounds "c'olesterolsteroid 'oronesatt&acids5

4 Exogenous copounds " drugs ood

addicti0escoponents o cigaretteso6e pesticides and c'eicals usedor industr& t'at enter t'e bod& b&ingestion o oods in'alation orabsorption t'roug' t'e s6in5


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%Y) *+, in0ol0ed in "

4 75 8nacti0ation or acti0ation ot'erapeutic agents54 25 %on0ersion o c'eicals to 'ig'l&

reacti0e olecules 9'ic' a& produce

un9anted cellular daagecell deat' orutations54 :5 )roduction o steroid 'orones4 *5 Metabolis o att& acids

prostaglandins leu6otriens and retinoids54 +5 En3&e in'ibition or induction t'at

results in drug-drug interactions andad0erse eects


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General reaction catal&3ed b& a %Y)*+, is9ritten as ollo9s "

4 ;# $ O2 $ NA.)# $ #$ ; 4O# $NA.)$ $ #2O

4


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General =eatures o %&toc'roe


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General =eatures o %&toc'roe)*+, %atal&sis

75 Substrate binding (presuabl& near t'e site ot'e 'ee ligand!

25 7-electorn reduction o t'e iron b& la0proteinNA.)# c&toc'roe )*+, reductase

:5 ;eaction o errous iron 9it' O2 to &ield anunstable =eO2 coplex*5 Addition o t'e second electron ro NA.)# or

c&toc'roe b++5 #eterol&tic scission o t'e =eO-O(#! bond to

generate a oral (=eO!:$>5 Oxidation o t'e substrate5

75 =oral abstraction o '&drogen ato or electron25 ;adical recobination

?5 ;elease o t'e product5


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7ru%$C@P

; O2 7ru%O$ ; -2O

6A7P- 6A7P


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%Y) *+, Noenclature

and terinolog& 8ndi0idual c&toc'roe )-*+, en3&es areclassiied b& t'eir aino acid siilarities and aredesignated b& a ail& nuber a subail& letter

a nuber or an indi0idual en3&e 9it'in t'esubail& and an asteris6 ollo9ed b& a nuberand a letter or eac' genetic (allelic! 0ariant(ore inoration is a0ailable at9995i56i5se/%Y)alleles/!5 =or exaple "

%Y)2.>@7ageneidentiied in 7B* encodes t'e9ild-t&pe protein %Y)2.>575


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Genetic pol&orp'iss o ) *+,en3&es deecti0e ) *+, proteins

deecti0e drug etabolis


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C'& %Y) *+, 'ot topicsD Metabolic roles o t'ese 0arious en3&es inorgans in 9'ic' t'e& unction5

%Y) *+, oxidi3ed exogenous lipop'ilicsubstrates " drugsc'eicals used in

9or6placeindustrial b&productsoodaddicti0esen0ironental containants5

%Y) *+, in'ibitors " pre0ent etabolis o

endogenous and exogenous copounds5 8n'ibition a& altered t'e etabolis o drug

ro its predicted rate --- drugaccuulationad0erse eect5


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%onseuences o %Y) *+, in'ibition " drug-drug interaction and ad0erse eects5

4


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Mitoc'ondrial c&t )*+, s&stes insteroidogenic tissues bios&nt'esis

o steroid 'orones ro c'olesterol Mitoc'ondrial c&t )*+, s&stes in

6idne& etabolis o 0itain .

Mitoc'ondrial c&t )*+, s&stes inli0er bios&nt'esis o bile acid


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Superoxide ree radicals (O2-!

Generated ro transer o a single

electron to O2 8t is ored reduced la0in are

reoxidi3ed uni0alentl& b& olecular ox&gen Superoxide disutasein aerobic

organiss reo0al O2- t'e reaction"O2-$ O2-$ 2#$#2O2$ O2

Superoxide can reduce oxidi3ed c&t c"

O2- $ c&t c (=e:$! O2 $ c&t c (=e2$! Exposure to an atosp'ere o 7,,

ox&gen causes an adapti0e increase insuperoxide disutase


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Biology Oxidation 1