metabolism of the eicosanoids

8/19/2019 Metabolism of the Eicosanoids

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METABOLISMMETABOLISM

OF THEEICOSANOIDS

Floro B. Madarcos, MD


2/18


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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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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


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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metabolism of the eicosanoids

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