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METABOLISMMETABOLISM
OF THEEICOSANOIDS
Floro B. Madarcos, MD
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II. ARACHIDONIC ACIDII. ARACHIDONIC ACID
STRUCTURESTRUCTURE
COOHCOOH
CHCH
CHCH22
CHCHCHCHCHCH
CHCH
##// --
%#%#
$$
%%%% %!%!%2%2 2020
%%
20Car1o* ao20Car1o* ao
!do31l 1o*ds!do31l 1o*ds(20!(20!"" #, $, %%, %!#, $, %%, %!))
++- FA- FA
22%%%0%0%/%/
!!%$%$
%4%4%-%-
CHCH
CHCH
CHCH22
CHCH22 CHCH22CHCH22
HH22CC
CHCH22CHCH22
CHCH22 CHCH22CHCHCHCH
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III. CHARACTERISTICS OFIII. CHARACTERISTICS OF THE EICOSANOIDSTHE EICOSANOIDS
• Local 5oro*sLocal 5oro*s• A3ocr'* r63laorsA3ocr'* r63laors
•D'77'c3l o s3d8D'77'c3l o s3d8• 9ar'a1l 77cs9ar'a1l 77cs
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I9. CLASSES OFI9. CLASSES OF
THE EICOSANOIDSTHE EICOSANOIDS
• Prosa6la*d'*s (P:sProsa6la*d'*s (P:s))
• T5ro1o;a*s (T
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9. S>NTHESIS OF THE EICOSANOIDS9. S>NTHESIS OF THE EICOSANOIDS
O3r la8r O3r la8r Cll M1ra*Cll M1ra*
I**r la8r I**r la8r P H O S P H O L I P I D (Pho!ha"#$yl#no#"ol%P H O S P H O L I P I D (Pho!ha"#$yl#no#"ol%
Arac5'do*'c Ac'dArac5'do*'c Ac'd
Pho!hol#!a& APho!hol#!a& A2 2
P'o"alan$#n H P'o"alan$#n H 2 2 yn"ha& (P)H yn"ha& (P)H 2 2 S%S%
P'o"alan$#n H P'o"alan$#n H 2 2 yn"ha& (P)H yn"ha& (P)H 2 2 S%S%
P::P::22(Prosa6la*d'* :(Prosa6la*d'* :22))
Cy*loo+y&na& (CO,%Cy*loo+y&na& (CO,%
P:HP:H22(Prosa6la*d'* H(Prosa6la*d'* H22)?)?
T
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C>TOTECC>TOTEC @ @ (M'sorosol)(M'sorosol)
S>NTHETIC PROSTA:LANDIN (P:ES>NTHETIC PROSTA:LANDIN (P:E22))
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9ODA9ODA
(C>CLOO:ENASE INHIBITOR)(C>CLOO:ENASE INHIBITOR)
P:EP:E22
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9I. CLEA9A:E OF ARACHIDONIC ACID FROM9I. CLEA9A:E OF ARACHIDONIC ACID FROM
MEMBRANE PHOSPHATID>LINOSITOLMEMBRANE PHOSPHATID>LINOSITOL
OO
IIII
%%CHCH22 O O C C R C C R%% II
RR22 C O C O 22CC H H
II
CHCH22 O O P O P O
II
OO OHOH
OHOH
OHOH
OHOH
OHOH
H HHH
OHOH
HH
HHHH
OO
IIII
A'a*h#$on#* a*#$ A'a*h#$on#* a*#$
(204%(204%
S#"& o *l&aa& y S#"& o *l&aa& y
Pho!hol#!a& APho!hol#!a& A2 2
Stearic acidStearic acid
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COOHCOOH
CHCH
CC CCCCCC
CC
CC
CC
CC
CCCC
CCCC CCCCCC
CCCC
CC
##// --
%#%#
$$
%%%% %!%!%2%2 2020
%%22
%%
%0%0
%/%/
!!
%$%$%4%4%-%-
9II. CON9ERSION OF ARACHIDONIC9II. CON9ERSION OF ARACHIDONIC
ACID TO P::ACID TO P::22 AND P:HAND P:H22
OOHOOH
OO
OO
COOHCOOH
OHOH
OO
OO
COOHCOOH
ARACHIDONIC ACIDARACHIDONIC ACID Cy*loo+y&na&Cy*loo+y&na&
( ( CO, CO, % %2O 2O 2 2
PROSTA:LANDIN :PROSTA:LANDIN :22 (P::(P::22))P&'o+#$a&P&'o+#$a&
2 2 &&- -
PROSTA:LANDIN HPROSTA:LANDIN H22 (P:H(P:H22))
##--
##--
CHCH
CHCH
CO,-1CO,-1
CO,-2 CO,-2
NSAIDSNSAIDS
ASAASA
I137ro*I137ro*
I*do5aI*do5a
c'*c'*
P*8l13aP*8l13a o*o*
NSAIDSNSAIDS
Slc'Slc'
CO
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PROSTA:LANDIN HPROSTA:LANDIN H22 (P:H(P:H22))
OHOH
OO
OO
COOHCOOH##--
CHCH
OHOH
OHOH
OO
COOHCOOH##--
CHCH
P:EP:E22
P:FP:F22ααOHOH
OHOH
OHOH
COOHCOOH##--
CHCH
9III. CON9ERSION OF PROSTA:LANDIN H9III. CON9ERSION OF PROSTA:LANDIN H22TO P:ETO P:E22 AND P:FAND P:F22αα
Io/&'a&Io/&'a&
& $ * " a & & $ * " a &
HH
HHHH
HH
HHHH
HH
HH
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OHOH
OO
OO
COOHCOOH##--
CHCH
PROSTA:LANDIN HPROSTA:LANDIN H22 (P:H(P:H22))
OOCOOC
OO
OHOH
HOHO
PROSTAC>CLINPROSTAC>CLIN22
(P:I(P:I22
))
(or Prosa6la*d'* I(or Prosa6la*d'* I22))
OHOH
OO
OO
COOHCOOH##--
CHCH
THROMBO
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FOR THE S>NTHESIS FOR THE S>NTHESIS
OF THE LEUOTRIENES (#HPETE G #HETE)OF THE LEUOTRIENES (#HPETE G #HETE)
ARACHIDONIC ACIDARACHIDONIC ACID
COOHCOOH
CHCH
CC CCCCCC
CC
CC
CC
CC
CCCC
CCCC CCCCCC
CCCC
CC
##// --
%#%#
$$
%%%% %!%!%2%2 2020
%%
22
%%
%0%0
%/%/
!!
%$%$%4%4%-%-
5 5 - - L#!o+y&na&L#!o+y&na&OO22
COOHCOOH
CHCH
CC CCCCCC
CCCC
CC
CC
CCCC
CCCC CCCCCC
CCCC
CC
##// --
%#%#
$$
%%%% %!%!%2%2 2020
%%22
%%%0%0
%/%/
!!%$%$
%4%4%-%-
OOHOOH
#HPETE (#58dro;8ro;8'cosara*o'c ac'd)#HPETE (#58dro;8ro;8'cosara*o'c ac'd)
COOHCOOH
CHCH
CC CCCCCC CC
CC
CC
CC
CCCC
CCCC CCCC
CC
CC
CC
CC
##// --
%#%#
$$
%%%% %!%!%2%2 2020
%%
22%%
%0%0
%/%/
!!%$%$
%4%4%-%-
OHOH
#HETE (#58dro;8'cosara*o'c ac'd)#HETE (#58dro;8'cosara*o'c ac'd)
S!on"an&oS!on"an&o
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S OFS OF
PROSTA:LANDIN S>NTHESIS (A)PROSTA:LANDIN S>NTHESIS (A)
A. LINOLEIC ACIDA. LINOLEIC ACID
(%$2(%$2""/,%2/,%2))
LINOLEIC ANDLINOLEIC AND
LINOLENIC ACIDSLINOLENIC ACIDSPROSTA:LANDINSPROSTA:LANDINS
C20C20
-,/,%2-,/,%2P:E%
&lona"#on&lona"#on o+y&na"#ono+y&na"#on
$&a"'a"#on$&a"'a"#on *y*l#&$ *y*l#&$
B.B. LINOLENICLINOLENIC
ACIDACID
(%$(%$"",-,/,-,/))C20#C20#
#,$,%%,%!,%4#,$,%%,%!,%4P:E, P:Fα
$&a"'a"#on$&a"'a"#on
&lona"#on&lona"#ono+y&na"#ono+y&na"#on
*y*l#&$ *y*l#&$
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S OFS OF
PROSTA:LANDIN S>NTHESIS (B)PROSTA:LANDIN S>NTHESIS (B)
LINOLEIC ANDLINOLEIC AND
LINOLENIC ACIDSLINOLENIC ACIDSPROSTA:LANDINSPROSTA:LANDINS
C. D'5ooC. D'5ool'*ol'*o
l*'c ac'dl*'c ac'd
(20(20""$,%%,%!$,%%,%!))
P:E%
&lona"#on&lona"#on
o+y&na"#ono+y&na"#on
$&a"'a"#on$&a"'a"#on
*y*l#&$ *y*l#&$
P:F%α
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REFERENCES
• B'oc5'sr8, by Voet and Voet, 3rd ed.• L''*coJs Ill3srad B'oc5'sr8, Chance,
P. C. et al., 4th ed.
• HarrJs Ill3srad B'oc5'sr8, Murray, R.K. et. al., 28th ed.• Pr'*c'ls o7 B'oc5'sr8, Horton, H. R., et.
al., 4th ed.• B'oc5'sr8, Berg, Tyoc!"o, #tryer, $th ed. %.
$43&$44.• T;1oo= o7 B'oc5'sr8, 'e(l)n, T, M., *th
ed., *3*&*4+.
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