Klinická biochémia - nové trendy Oxidačný stres vo …...Klinická biochémia - nové trendy...

Klinickaacute biocheacutemia -

noveacute trendy

Oxidačnyacute stres vo fyzioloacutegii a v patogeneacuteze niektoryacutech ochoreniacute

(Ako ho rozpoznať a ako sa proti nemu braacuteniť)

1 časť

Povinne voliteľnyacute predmet pre študentov doktorandskeacuteho štuacutedia 201718

Voľneacute radikaacutely

Vznik života na zemi

Deštrukčneacute laacutetky uacutečinneacute pri zaacuteniku živyacutech organizmov

Pred35 miliardami rokov


Primitiacutevne molekuly Dedičneacute zmeny

Protobunky Odumreteacute bunky

Vyacuteživa

ŽIVOT


O2 gt 1AminokyselinyNukleotidy

Naacutehodneacute zmeny v protobunkaacutech





Vyacuteživa

ŽIVOT




RADIKAacuteL

jest shluk prvků chemickyacutech kteryacutež zesloučeniny chemickeacute do jineacute sloučeninypřenaacutešeti umiacuteme a jenž maacute určitou sytivostchemickou vyplyacutevajiacuteciacute z valence prvků

Sudomocneacute radikaacutely jsou u volneacutem stavuschopny existence radikaacutelů lichomocnyacutechisolovati nelze jakmile se ze sloučeninyvybaviacute ihned spolu se slučujiacute

Ottův SLOVNIacuteK NAUČNYacute dvacaacutetyacute paacutetyacute diacutel 1904

Odvodeneacute od dusiacuteka

bullnitroxid (NO)bullnitroperoxid (NOO)

bullperoxynitritovyacute anioacuten (ONOO-)

Odvodeneacute od kysliacuteka

bullsuperoxid (O2-)

bullhydroxylovyacute radikaacutel (HO)

bullsingletovyacute kysliacutek (1O2)

bullperoxid vodiacuteka (H2O2)

Voľneacute radikaacutely a ROS

Tvorba superoxidoveacuteho anioacutenoveacuteho radikaacutelu (superoxidu)

+

O2 + elektroacuten O2-redukcia

Štvorelektroacutenovaacute redukcia kysliacuteka

Kysliacutek Superoxid Peroxid vodiacuteka Hydroxylovyacute Vodaradikaacutel

Superoxiddismutaacuteza Katalaacuteza

Vzaacutejomneacute reakcie voľnyacutech radikaacutelov areaktiacutevnych metabolitov

O 2

H 2O 2bullOHO 2 bull

-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH

Superoxidovyacute anioacutenovyacute radikaacutel

Peroxidvodiacuteka

Hydroxylovyacute radikaacutel

HOCl 1O 2

H 2O

Cl bull

H 2O 2

+

Kyselina chloacuterna Singletovyacute kysliacutek

NO OONO bull-HOONO

NO 2bull

Oxid dusnatyacute Peroxynitrit

Oxiddusičityacute

Kyselina dusičnaacute

Dvojakaacute uacuteloha voľnyacutech radikaacutelov a ich reaktiacutevnych

metabolitov

Voľneacute radikaacutely ndash negatiacutevna funkcia

bull ak sa tvoria vo veľkom množstve

bull ak sa tvoria na nespraacutevnom miest

bull ak suacute v bliacutezkosti ioacuteny prechodnyacutech prvkov

bull ak zlyhaacute ochrana organizmu

Voľneacute radikaacutelyRM ndash pozitiacutevna funkcia

bull Reprodukcia (O2- H2O2)

bull Fagocytoacuteza (O2- H2O2 OH )

bull Signaacutelne funkcie

bull Hydroxylačneacute karboxylačneacute peroxidačneacute

reakcie (hydroxylaacutecia proliacutenu lyziacutenu (- Fe(II)-O2 Fe(III)-O2- )

a redukcia ribonukleotidu(ribonukleoziddifosfaacutetreduktaacuteza RR-S )

VONKAJŠIE ZDROJE VR a RMK

bull Cigaretovyacute dymbull Znečistenie životneacuteho

prostrediabull Radiaacuteciabull Chemoterapeutikaacutebull Ozoacutenbull Niektoreacute pesticiacutedy

organickeacute rozpuacutešťadlaacute

VNUacuteTORNEacute ZDROJE VR a ROS

bull Prenos elektroacutenov v dyacutechacom reťazci mitochondriiacute

bull Metabolizmus kyseliny arachidoacutenovejbull Reakcie cytochroacutemu P450bull Systeacutemy middotNO syntaacutezybull Autooxidaacutecia katecholamiacutenovbull Zaacutepalbull Reakcie zahŕňajuacutece ioacuteny prechodnyacutech prvkov

Ďuračkovaacute (1998) Slovak Academic Press

(Fe-S)

FMN

KOMPLEX I NADH-dehydrogenaacuteza

KOMPLEX IIsukcinaacutetdehydrogenaacuteza

KOMPLEX IIIubichinol-cytochroacutem c -reduktaacuteza

KOMPLEX IVcytochroacutem c-oxidaacuteza

KOMPLEX V ATP-syntetaacuteza

Q

NADHGlutamaacutetPyruvaacutet3-hydroxybutyraacutet

(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP

Vnuacutetromitochondriovyacute priestor

Vnuacutetornaacutemitochondriovaacutemembraacutena

Cytoplazma

Q

ProteiacutenmtDNALipid

O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-

Tvorba voľnyacutech radikaacutelov v dyacutechacom reťazci mitochondriiacute

Ak nie je dostato čnaacute ochrana -ROS uacutečinkujuacute v mitochondriaacutech aj mimo ne

Mn-SOD

Schematic representation of a phagocyte engulfing a microbe into a phagocyte vacuole

The NADPH oxidaseis selectively activated in the wall of the vacuole generating superoxide and hydrogen peroxide in the vacuolar lumen

Balaraman Kalyanaraman

httpdxdoiorg101016jredox201301014

Tvorba superoxidupočas fagocytoacutezy

Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP

NOSkatalyzuje tvorbu nitroxidu

Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS

eNOS catalyses NO formation

The Nobel Prize in Physiology or Medicine 1998for their discoveries concerning nitric oxide as a signalling molecule in

the cardiovascular system

Robert F Furchgott Louis J Ignarro Ferid Murad

1916 ndash 2009 1941 - 1936 ndash

USA USA USA

Biologickeacute uacutečinky NO

NO-syntaacuteza

NOO2

L-arginiacuten L-citruliacuten

Regulačneacute(fmol-pmol)

NeurotransmiterPrenos nervoveacuteho vzruchu

Cievny tonusOvplyvnenie imunitnyacutech

mechanizmovPermeabilita cievnej steny

ŠkodliveacuteProoxidačneacute (nnmol)

Inhibiacutecia enzyacutemovPoškodenie DNA lipidov proteiacutenovZniacuteženie antioxidačnej kapacityZvyacutešenie citlivosti voči radiaaacutecii

alkylačnyacutem činidlaacutemtoxickyacutem kovom

H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O

Pozitiacutevna funkcia NO

cGMP

Toxickosť reakcie superoxidu s NO

Proposed mechanism for ischemia-induced formation of reactive oxygen species



Uric acid

HO

HO

CH CH2 NH2

OH

NoradrenaliacutenFMN

NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH

Kyselina 34-dihydroxymandlovaacute

COMT

S-adenozylmetioniacuten

O

HO

CH COH

O

OHH3C

Kyselina vanilmandlovaacute

Obr Tvorba peroxidu vodiacuteka počas degradaacutecie katecholamiacutenov MAO-monoaminooxidaacuteza COMT-katechol-O-metyltransferaacuteza

34-dihydroxyfenylglykoaldehyd

Tvorba H2O2

pri degradaacutecii

katecholamiacutenov

Fentonova a Haber-Weissova reakcia

PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE

Lipoperoxidaacutecia

ROS

(Fe2+ Cu+)MDA

4HNE

pentaacuten hexaacuten

ProteiacutenyNH2

SH

zosieťovanie proteiacutenov

H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA

LipoperoxidaacuteciaR 1

R 2Fosfolipid LH

Alkylovyacute radikaacutel

Konjugovanyacute dieacutenalkyloveacuteho radikaacutelu

Peroxylovyacute radikaacutel

O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH

Peroxylovyacute radikaacutelAlkoxylovyacute radikaacutel

Hydroperoxid

AlkanalyAlkenaly(4-HNE MDA)

štiepenie

R 2O

H

Alkenylovyacute(alebo alkanylovyacute)radikaacutel Alkenal

modifikaacutecia biomolekuacutel

O 2

Komplex Fe(II) Komplex Fe(III)

R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny

Alkaacutenypľuacuteca

bullminus bull bullO2 OH R

trans-hydroxynonenal

MDA

8-isoprostaacuten

Produkty oxidačneacuteho poškodenia kyseliny arachidoacutenovej

Zložky lipidovMastneacute kyseliny

Nasyacuteteneacute (viac zastuacutepeneacute v tukoch)(kys palmitovaacute kys stearovaacute)ndash stabilnejšie ndash maacutelo citliveacute na oxidaacuteciundash ťažšie straviteľneacute

Nenasyacuteteneacute (obsahujuacute dvojituacute vaumlzbu)(viac zastuacutepeneacute v olejoch)

(kys olejovaacute kys linolovaacute kys linoleacutenovaacute) ndash menej staacutelendash ľahšie straviteľneacute ndash citliveacute na oxidaacuteciu (voľnyacutemi radikaacutelmi)

okrem kyseliny olejovej (C181)

Vyacuteznam zloženia PUFAANTIOXIDA ČNE Kyselina olejovaacute C181 (cis)

Nasyacuteteneacute vyššie karboxyl kyseliny

PROOXIDAČNE ndash nenasyacuteteneacute

Omega ndash 3 Rybie olejekyselina linoleacutenovaacute C183

kyselina dokozahexaeacutenovaacute C226

kyselina eikozapentaeacutenovaacute C205

Omega ndash 6 Rastlinneacute olejekyselina linolovaacute C182

kyselina archidoacutenovaacute C204

COOH

Porucha integrity bunky

Rakovina

Kardiovaskulaacuterne ochorenia

Metabolickyacute syndroacutem

Diabetes mellitus

Psychickeacute poruchy

Porucha v zloženiacute

membraacuteny

Bunkovaacute membraacutena

Synteacuteza PUFAs z kys linolovej LA C182 ω-6 akys α-linoleacutenovej ALA C183 ω-3

Kys linolovaacute LA C182 ω-6

Kys dokozatetraeacutenovaacute C224

Kys dokozapentaeacutenovaacute C225

∆4 desaturaacuteza

elongaacuteza

Kys linoleacutenovaacute ALA C183 ω-3

Kys arachidoacutenovaacute AA C204 ω-6

Kys λ -linoleacutenovaacute GLA

Kys dihomo-λ-linoleacutenovaacute DGLA



elongaacuteza

581114COOH20

Kysstearidoacutenovaacute C184

Kys eikozatetraeacutenovaacute C204

Kys eikozapentaeacutenovaacute EPA C205 ω-3



elongaacuteza

Kys dokozapentaeacutenovaacute C225 ω-3

Kys dokozahexaeacutenovaacute DHA C226 ω-3


elongaacuteza

37

Synteacuteza kys linolovej LA C182 ω-6 a kys α-linoleacutenovej ALA C183 ω-3

Kys linoleacutenovaacute ALA C183 ω-3Kys linolovaacute LA C182 ω-6




Kys dokozatatraeacutenovaacute C224



Kys eikozatatraeacutenovaacute







elongaacuteza

elongaacuteza

COX2 5-LOXTvorba pro-zaacutepaľovyacutech PG2

TXA2 LTB4

COX2 Tvorba proti-zaacutepaľovyacutech PG1

a TXA1COX2 5-LOX

Tvorba proti-zaacutepaľovyacutech PG3 TXA3 LT5

38

NeuroprostaacutenyResolviacuteny ndash blokujuacute tvorbu

prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA

Pro-zaacutepaloveacute

a

Proti-zaacutepaloveacute

eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2

Kompetiacuteciacutea zabudovania do membraacuteny

PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA

Bioaktiacutevneprodukty

PMNL ndashchemotaxia

Trombocyty - P-selektin

expresia-TrombocytLeuko

cyt interakcia

Isch- rep poškodenie orgaacutenov

- PMNL-Transmigraacuteci

a cez endotel

- Eferocyoacuteza apoptickyacutech

PMNL

COX2

41

Fyzikaacutelny vplyv rocircznych MK na funkciu buniek

Fluidita - tekutosť

Ohyacutebanie Rotaacutecia Bočnaacute difuacutezia Poskakovanie Obaacutetenie sa

(flexion) (lateral diffusion) (bobbing)

42

Spektrum mastnyacutech kyseliacuten v rastlinnyacutech olejoch

palmitovaacute steaacuterovaacute olejovaacute linolovaacute linoleacutenovaacute DHA

Slnečnicovyacute 91 37 271 601 ndashndashndash- 05

Olivovyacutepanenskyacute

198 83 512 176 28 ndashndashndash

Soacutejovyacute 130 31 250 487 101 ndashndashndash

Repkovyacutepanenskyacute


Ľanovyacutepanenskyacute


Mandľovyacute 77 20 522 382 05 07

Nasyacuteteneacute Nenasyacuteteneacute

Spektrum mastnyacutech kyseliacuten v tukoch

palmitovaacute steaacuterovaacute olejovaacute linolovaacute linoleacutenovaacute Arachidoacute-novaacute

EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť

243 79 502 166 23 01 ndashndash- ndashndash-

Bravč masť

257 178 428 108 23 06 ndashndash-- ndashndash-

Bravč masť mangalica


Olivovyacute olej

198 83 512 176 28 ndashndashndash ndashndash- ndashndash-


ZAacuteVER bull Zmena stravovania (Western nutrition) ndash naacuterast KVO a psychickyacutech

poruacutechbull KVO a psychickeacute ochoreniandash viacereacute spoločneacute patofyzilogickeacute znaky

- tvorba pro-zaacutepalovyacutech cytokiacutenov- endotelovaacute dysfunkcia- tvorba HCy- abnormality v prietoku krvi (u dpresie ndash hypoperfuacutezia v limbickom

systeacuteme a prefrontal cortex- utilizaacutecia glukoacutezy v niektoryacutech oblastiach mozgu

Spoločnyacute menovateľ ndash zmena konzumaacutecie a pomeru omega-6 ku omega-3 MK

Suplementaacutecia omega-3 MK ndash bezpečneacute jednoducheacute relatiacutevne lacneacute45

Pozor ndash fajčenie inhibuje inkorporaacuteciu omega-3 do erytrocytov

Suplementy omega-3 MK (Raatz a kol 2009)

- emulzia ndash lepšie sa absorbujuacute omega-3 MK lepšiacute priacutestup lipaacutez mocircže sa upraviť chuť aditiacutevami

- tobolky kapsulky- triacylglyceroly z rybieho oleja ndash polovičneacute využitie - ako u emulzie

Nežiaduce uacutečinky dlhodobeacute vysokeacute daacutevkybull dyskomfort GIT ndash riedka stolica hnačka nevoľnosť zvracanie

nechutenstvobull krvaacutecanie do GITu ndash odporuacuteča sa 3-7 dniacute pred operaacuteciou užiacutevanie v

vynechaťbull nedostatok vitamiacutenu E ndash doplnkovaacute suplementaacuteciabull užiacutevať s jedlom

46

V suacutečasnosti sa odporuacutečaAmerickaacute Psychiatrickaacute SpoločnosťDennyacute priacutejem omegandash3 = minimaacutelne 1gFDA (Food and Drug Administration)Dennaacute daacutevka omega-3 dospelyacutem - 3 g European Food Safety AuthorityDennaacute daacutevka omega-3 (EPA+DHA+DPA) pre dospelyacutech ndash 5 g

Majuacute status GRAS

pre dospelyacutech

Minimaacutelne daacutevky omega-3 MK (Global Recommendations for EPA and DHA Intake -1642014)Dospelyacute Euroacutepan ndash 250 mg EPA+DHA denneTehotneacute a dojčiace ženy ndash 100-200 mg DHA denne Deti 7-24 mesiacov ndash 100 mg DHA denneDeti 2-18 rokov ndash 250 mg EPA+DHA denne

47

Pomer omegandash6 omegandash3 = 2 1 ndash optimumNemal by prekročiť 5 1 Lepšie je omega-6 zniacutežiť ako omega-3 zvyacutešiť

Kardioloacutegovia odporuacutečajuacute pre omega-3 pomer DHA EPA = 2 1

Sledovať informaacutecie na priacutebalovom letaacuteku

Pri psychickyacutech poruchaacutechndash EPADHA = 6040

Odporuacutečania

Sinopoulos 2002 Grosso a kol 2014 Farouuqui et al 2009 Gow a Hibbeln 2014Zaacutevery WHO FDA EFSA a inyacutech

Tyacuteždenne 2 ndash 3 jedlaacute z ryacuteb

48

Oxidačneacute poškodenie proteiacutenov

PRIMAacuteRNEbull reakcie katalyzovaneacute ioacutenmi prechodnyacutech prvkovbull radiaacutecia ozoacuten bull oxidy dusiacuteka bull HOCl

SEKUNDAacuteRNEProteiacuteny suacute modifikovaneacute produktmi oxidaacutecie inyacutech molekuacutel (vaumlzba 4HNE a MDA na -NH2 a -SH skupiny)

donor elektroacutenov

H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy

Aminokyseliny Peptidy

CH2NH2

Fe(II)proteiacuten C OHproteiacuten

CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22

Tvorba karbonylov proteiacutenov katalyzovanaacute ioacutenmi Fe


OXIDAČNYacute ZAacuteSAH DNA

Ľudskaacute bunka metabolizuje denne 1012 molekuacutel O2

Tvoriacute 3x109 molekuacutel H2O2

Oxidačne sa zasahuje 2x105

nukleotidovbunkudeň

bullOxidačneacute poškodenie puriacutenovyacutech a

pyrimidiacutenovyacutech zaacutesad

bull Oxidačneacute poškodenie deoxyriboacutezovej

jednotky (C4-d riboacutezy)

bull Jednovlaacuteknoveacute alebo dvojvlaacuteknoveacute

zlomy DNA

OXIDAČNEacute POŠKODENIE DNA

Hlavneacute produkty oxidačnho poškodenia DNA

Fapy ndash 24-diamiacuteno-5-formamido-6-oxopyrimidiacuten

HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym

8-oxo-dG10 G Lymphocytes8-oxo-dG106G Lymphocytes

HPLC HPLCLaboratory Country n mean SE

2 Italy 16 451 1004 Belgium11 360 0675 Slovakia 17 651 0466 Slovakia 20 665 06413 England 3 020 02014 Denmark 20 425 03228 Denmark 17 589 07415 Sweden 16 124 01016 Poland 20 423 03521 Spain 16 051 00321 Spain 16 030 001

Results of ESCODD project 5FP EU Collins et al ABB 423 57-65 2004

Mutagenesis of 8-oxo-dG

-G -OxodGC- -OxodG A-C-C-

OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS

OxodG rotates into syn

dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM

Regioacuteny Slovenska

Sum

a po

škod

enia

Oxidačneacute poškodenie DNA u detiacute (10 ndash 13 rokov) v rocircznych regioacutenoch Slovenska (n = 18-20)

DS ndash Dunajskaacute Streda BA = Bratislava NM = Noveacute Mesto n Vaacutehom


Vznik života na zemi

Deštrukčneacute laacutetky uacutečinneacute pri zaacuteniku živyacutech organizmov





Vyacuteživa

ŽIVOT








Vyacuteživa

ŽIVOT




RADIKAacuteL








bullsuperoxid (O2-)






+






O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







Vyacuteživa

ŽIVOT








Vyacuteživa

ŽIVOT




RADIKAacuteL








bullsuperoxid (O2-)






+






O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







Vyacuteživa

ŽIVOT




RADIKAacuteL








bullsuperoxid (O2-)






+






O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



RADIKAacuteL








bullsuperoxid (O2-)






+






O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







bullsuperoxid (O2-)






+






O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




+






O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







O 2


-O 2 H 2O

bullH R bull

RH

SOD

e bull Fe 2+Fe 3+

OH


Peroxidvodiacuteka


HOCl 1O 2

H 2O

Cl bull

H 2O 2

+


NO OONO bull-HOONO

NO 2bull


Oxiddusičityacute



metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




metabolitov





















(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia























(Fe-S)

FMN






Q


(Fe-S)

FAD

Sukcinaacutet

(Fe-S)

2Hb

c1

C

H+

a - Cu

a3 - Cu

O2H 2O 12

ADP ATP



Cytoplazma

Q


O2-

O2

H 2O2 OH

QH

QH2

Fe(II)

Fe(III)

MnSOD

OH

Fe2+

O2O2-

O2O2-

O2O2-



Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




Mn-SOD






Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia








Tvorba O2-

NADPH-oxidaacutezou

v membraacutene

neutrofilu

NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



NADPH

NADP+

FAD BH4

FMN Fe

NOS

L- arginineO2

L -citrulline

NO

XOxantine uric acid

O2 H2O2

Xanthine oxidase

Sup

erox

ide-

gene

ratin

g en

zym

esA

ntio

xida

nt e

nzym

es

AA

PLA2

Lipoxygenase

1215-LO

COO

H

5-LO

proinflammatory LTs

O2-

O2

p67rac

NOX

1 4p22

NADPH NADP+

NAD(P)H oxidase

p47

e-

e- e- e- e-

Mitochondria

NADH

NAD+

H2O

O2

I II IVII

Q C ATP


Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




Ko-faktory NOS

bull BH4

bullHem

bullFMN

bullFAD

bullkalmoduliacuten

eNOS

nNOS

iNOS





1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







1916 ndash 2009 1941 - 1936 ndash

USA USA USA


NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




NO-syntaacuteza

NOO2









H2NCH

COOH

(CH2)3NHC

H2N NH

H2NCH

COOH

(CH2)3NHC

H2N O


cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




cGMP





Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







Uric acid

HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



HO

HO

CH CH2 NH2

OH


NH3

FMNH2

O2H2O2

H2O

HO

HO

CH COH

O

H

H2O

H2O2

O2 FMNH2

FMN

MAO

MAO

HO

HO

CH COH

O

OH


COMT


O

HO

CH COH

O

OHH3C




Tvorba H2O2

pri degradaacutecii

katecholamiacutenov


PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




PROTEIacuteNOV

DNA

LIPIDOV

POŠKODENIE


ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




ROS

(Fe2+ Cu+)MDA

4HNE


ProteiacutenyNH2

SH


H2N-apoA-I pre HDL


H2N-apoA-I pre HDL

PUFA

FLCE

LDL

PUFA

H

O2

PUFA

O2

PUFA

O-O

PUFA

OOH

Hydrolipoperoxid

PUFA


R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




R 2Fosfolipid LH




O O

malondialdehyd(MDA)

R 1

R 2

OOH

LOOH


Hydroperoxid


štiepenie

R 2O

H



O 2


R

RH

L

L

LOO

R 1

R 2

R 1

R 2

R 1

R 2

OO

RH

R

R 2

O O

R 1

R 1

R 2

O

LO

R 1

R 2

OO

LOO

R 1

RH

R

Alkeacuteny




MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia





MDA

8-isoprostaacuten















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia
















COOH


Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia




Rakovina



Diabetes mellitus



membraacuteny







elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia








elongaacuteza







elongaacuteza

581114COOH20






elongaacuteza




elongaacuteza

37
















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia


















elongaacuteza

elongaacuteza


TXA2 LTB4


a TXA1COX2 5-LOX


38


prostanoidov

PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



PGF1

PGF1

α

PGF2

PGF2

α

PGF3

PGF3

α

DGLA

EPA

AA


a


eikozaacutenoidy

39

POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



POTRAVAALALA

COX2 LOX

AA

PG2 TX2 LT4

PhL A2


PhL A2

EPA menej DHA

COX2 LOX

PG3 TX3 LT5

40

GLA

DGLA

AA

D6D

D5DEPA

D6DD5D

D4DDHA





cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







cyt interakcia



a cez endotel


PMNL

COX2

41





42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







42











Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia













Mandľovyacute 77 20 522 382 05 07




EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia





EPA DHA

Rybiacute tuk 156 52 365 115 119 68 61 63

Kačacia masť


Bravč masť




Olivovyacute olej
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia
















46



pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia





pre dospelyacutech


47





Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







Odporuacutečania



48





H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia







H2O2

e-

Fe(III)

Fe(II)

H2OH+

e-2 CH2NH2

CH2NH2

OH-

Fe(III)proteiacuten

proteiacuten

H2O

NH3OH -

proteaacutezy


CH2NH2


CH NH

OH -

Fe(II)proteiacuten

CHNH2

OH-

Fe(III)proteiacuten

HO

H+O22













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia













zlomy DNA




HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia





HN HNN O

O

NH2

O

N

N OHNH2

N

N

HO

NH2

OH

H

HN

NH

O

O

CH3

OH

OH

H

FapyAde 8-OH-Gua

56-OH-Tym

H

H

5-OH-Cyt

N NNH2

H

45-OH-Tym







OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia









OxoG

C-

A-

dTTP

A- -TPool of mutant

DNA

ROS


dATP

DNA-ligase

hOgg1

endonuclease

0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



0

20

40

60

80

100

120

DS BA NM


Sum

a po

škod

enia



Klinická biochémia - nové trendy Oxidačný stres vo …...Klinická biochémia - nové trendy...

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Transcript of Klinická biochémia - nové trendy Oxidačný stres vo …...Klinická biochémia - nové trendy...