Antioxidant System

Antioxidant system
Cell Antioxidant Protection Factors
There is no single universal classification of antioxidants.
There is a point of view about several levels of protection of cells of the

microorganism from reactive oxygen species (Petrovich Yu.A., Gutkin DV,
1986):
Level 1 - systemic protection of cells due to a significant decrease in O2

voltage in the tissues compared to atmospheric air;
Level 2 - is provided in the process of four-electron reduction of the main mass
of intracellular O2 with the participation of cytochrome oxidase without the
release of free radicals;
Level 3 - enzymatic removal of the resulting superoxide anion radical and

H2O2;
Level 4 - the presence of free radical traps (antioxidants);
Level 5 - enzymatic reduction of polyunsaturated fatty acid hydroperoxides.
The number of endogenous antioxidant compounds is constantly increasing.
Some authors have made the following attempt to classify antioxidants (2

groups).
1. High Molecular Compounds:
- antioxidant protection enzymes - SOD, ceruloplasmin, catalase,

glutathione-dependent enzymes, provide comprehensive antiradical protection of
biopolymers.
Enzymatic antioxidants are characterized by high specificity, strictly

defined organ and cell localization, and the use of metals Cu, Fe, Mn, Zn, Se as
catalysts
- proteins capable of binding ions of Fe and Cu, which are catalysts for free
radical processes. These include blood albumin, transferrin, ferritin, lactoferrin,
ceruloplasmin. Reducing proteins - thioredoxins, etc.
Many of them are very effective, but weakly penetrate through the membranes
and tissue barriers
2. Low molecular weight antioxidants: some amino acids, polyamines, urea,
glutathione, ascorbic acid, bilirubin,-tocopherol, vitamins A, K, P, ubiquinone,
isoflavones, etc.
Enzyme protection
Superoxide dismutase (SOD; KF 1.15.1.1.) Catalyzes the reduction reaction of

the oxygen radical anion (· O2-) to hydrogen peroxide, i.e. It is a key enzyme in
the antioxidant system of aerobic organisms.
2·О2- + 2H+ → H2O2 + O2
In eukaryotic cells, SOD has several forms:
a) copper and zinc-containing SOD - localized in the cytosol, the

intermembrane space of mitochondria, lysosomes and peroxisomes;
b) manganese-containing SOD - localized in the mitochondrial matrix

and in prokaryotes;
c) later, an iron-containing enzyme, found only in prokaryotes, was also detected;

d) the extracellular form of SOD - functions in the blood plasma, lymph and
synovial fluid.
Catalase (Cat .; EC 1.11.1.6) has the ability to decompose hydrogen

peroxide in two ways: catalase or peroxidase.
In both cases, the process goes through the formation of an intermediate

enzyme-substrate complex (set 1).
Cat. + Fe3 + + H2O2 K1 (set 1)
Compl. 1 + H2O2 K2 Cat. -Fe3 + + 2H2O + O2
Set 1 + AH2 k2Kat.-Fe3 + + 2H2O + A
In the first case (catalase path – reaction 1, 2), the decomposition of 2 molecules of
H2O2 proceeds with the formation of H2O and triplet oxygen.
In the second (peroxidase pathway - reactions 1, 3), one molecule of H2O2 forms
an enzyme-substrate complex (set 1) and oxidizes the hydrogen donor (AH2).
Monohydric alcohols, organic hydrogen donors, xenobiotics, for example,
aminobiphenyls, etc. can act as hydrogen In the first case (catalase path – reaction
1, 2), the decomposition of 2 molecules of H2O2 proceeds with the formation of
H2O and triplet oxygen.
In the second (peroxidase pathway - reactions 1, 3), one molecule of H2O2 forms
an enzyme-substrate complex (set 1) and oxidizes the hydrogen donor (AH2).
Monohydric alcohols, organic hydrogen donors, xenobiotics, for example,
aminobiphenyls, etc. can act as hydrogen donors.
Peroxidases are a subclass of hemin enzymes. Hydrogen peroxide is
reduced to H2O, while reducing agent is oxidized.
The most active glutathione peroxidase (selenium containing enzyme).
The donor of hydrogen (the second substrate) is glutathione - γ-glutamyl-
cysteyl-glycine.
2Н2О2 + 2G-SH—> H2O + G-S-S-G
G-SH – reduced glutathione
G-S-S-G – oxidized glutathione.
Glutathione is regenerated with the participation of NADPH + H + and glutathione
reductase.
G-S-S-G + NADPH + H + —> 2G-SH + NADP+.
Along with the “classical” selenium-dependent glutathione peroxidase,
the body contains a number of other enzymes that perform a similar function,
this is glutathione transferase (EC 2.5.1.18). They catalyze the conjugation
of glutathione with numerous electrophilic substrates and the reduction of
organic hydroperoxides, including phospholipid peroxides, endoperoxides
(epoxides). Inactive against hydrogen hydroperoxide.
An important role in maintaining the redox balance in the cell is played

by thioredoxins, glutaredoxins, and peroxiredoxins.
Thioredoxins (TRX) are polyfunctional low-molecular proteins, having
in their structure a two-cysteine segment and forming an intramolecular
disulfide bond during oxidation. (Thus able to oxidize and recover).
Powerful antioxidants, regulators of apoptosis, cell metasis activity, etc.
The catalytic activity of peroxiredoxins and gultation peroxidases are
restored. Able to reduce H2O2 and oxidized glutathione, play the role of
"trap" ˙OH radicals.
Peroxiredoxins (thioredoxin peroxidases) is a widespread large family of

non-selenium antioxidant enzymes. Unlike thioredoxins, they do not have
double cysteine sites. Cysteine residues present in the structure of
peroxiredoxins are capable of forming intermolecular disulfide bonds.
The main function of peroxiredoxins is the restoration and detoxification
of H2O2, organic hydroperoxides and peroxynitrite.
In mammals, for example, they control the level of cytokine-induced

peroxides involved in the transmission of cellular signals.
Glutaredoxins are low molecular weight G-SH-dependent polyfunctional

oxidoreductases (9-14 kDa). In contrast, thioredoxins have a high degree of
amino acid sequence homology, especially in the region of the active center.
Functionally associated with the work of glutathione reductase and with the
ratio G-SH/GS-SG.
Like thioredoxins and peroxiredoxins, they play an important role in maintaining
cellular redox homeostasis. They neutralize ROS, participate in the regulation of
proliferation, differentiation and apoptosis.
Non-enzymatic components
antioxidant system
By the mechanism of action can be classified into the following groups:
- classical antioxidants (breaking the chain agents);
- traps initiators of free radical reactions;
- chelators (iron binding agents);
- cofactors and low-molecular components of protective antioxidant enzymes and
their precursors.
Vitamin E (tocopherol)
Tocopherols are involved in the destruction of free radicals in cells and

regulate the intensity of lipid peroxidation at various levels of the organization
of living systems. The most active antioxidants.
α-Tocopherol is able to react with ROS and fatty acid radicals. The reaction
takes part of the OH group of the phenol core, which is able to oxidize, donating
an electron, with the formation of a low-active free radical:
.
Tocopherol-OH + RO2 Tocopherol-O + ROH
Ascorbate
Dehydroascorbate
Tocopherol-OH
Vitamin C is a synergist. Ascorbate restores tocopherol, turning into

dehydroascorbate, the latter being restored by ascorbate reductase.
Vitamin C (ascorbic acid)
Vitamin S - the most effective water-soluble antioxidant.
In the stomach, it prevents the formation of nitrosoamines, which are
carcinogens, in the acidic environment of nitrites and amines. Prevents the
destruction of enzymes by free radicals, protects cells from oxidation.
Vitamin C participates in redox reactions, protecting hemoglobin from

oxidation, promotes collagen synthesis (hydroxylation reaction), ensures the
formation of adrenal hormones, bile acids. It is added to many beverages and
foods as an antioxidant and flavoring agent.
Retinol
cys and trans-retinal Retinoic acid
Flavonoids effectively neutralize radicals, due to the presence of hydroxyl

and carbonyl groups.
Able to accept free radicals and chelate metal ions of variable valence to
form complexes. The best known are quercetin, morin, taxifolin, silybin, etc.
Stimulate the production of antioxidants by the body itself.
Thanks to their presence, red wine is a good antioxidant (can be taken regularly in
small quantities), for example, helps prevent heart attacks.
Thiol-containing molecules make a major contribution to maintaining the
physiological values of ROS: glutathione, sulfur-containing amino acids.
Ubiquinone (coenzyme Q) has antioxidant activity, forming the redox
ubiquinol-ubiquinone.
Its most important biological role is determined by participation in the
mitochondrial electron transport chain as a coenzyme.
Antioxidant properties:
the reduced form (ubiquinol) may react with the peroxyl radical, preventing
the formation of alkyl radicals, which leads to the interruption of the POL
circuit;
• provides effective protection of membrane lipids, proteins and DNA from
the action of ROS;
• restores vitamin E, interacting with its tocopheroxyl radical;
• Ubiquinone is the only lipid-soluble antioxidant that is synthesized in cells
and is constantly regenerated from the oxidized form with the help of
enzyme systems of the body.
• High antioxidant activity was found in some hormones, in particular, those
containing the phenolic group of estrogens (female sex hormones) -
estradiol, estriol and estrone.
• The chemical modification of these compounds and the study of the
antioxidant and protective effects of the derivatives obtained during the
development of oxidative stress is a promising direction in creating new
antioxidants more effective than their endogenous counterparts.
• Melatonin - binds fat and water soluble radicals.
• Synthetic quinones, for example o-benzoquinone derivatives, have
pronounced biological activity. These compounds have a good protective
effect in conditions of ischemia of the brain, heart, and kidneys. They are
easily reduced by the components of the electron-transport chain of
mitochondria and microsomes to dioxybenzenes, which can easily donate
hydrogen atoms of hydroxyl groups for the reduction of radicals.
• Effective antioxidants are transporters of metals of variable valence
(ceuuloplasmin, transferrin, in particular lactoferrin, etc.).
• On their basis, new drugs are developed that have antioxidant properties in
combination with a low toxic effect.
• Ceruloplasmin is a copper oxidase, a copper-containing plasma protein that
plays an important role in the metabolism of copper and iron. It is
polyfunctional, has antioxidant properties, and is capable of destroying
superoxide oxygen radicals, preventing the activation of POL.
• The extracellular antioxidants include iron transporters and iron-binding
proteins - transferrin, lactoferrin, etc. While in the composition of these
proteins, iron does not catalyze free radical processes.

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Antioxidant system

Cell Antioxidant Protection Factors

There is no single universal classification of antioxidants.

There is a point of view about several levels of protection of cells of the

Level 1 - systemic protection of cells due to a significant decrease in O2

Level 3 - enzymatic removal of the resulting superoxide anion radical and

Some authors have made the following attempt to classify antioxidants (2

1. High Molecular Compounds:

- antioxidant protection enzymes - SOD, ceruloplasmin, catalase,

Enzymatic antioxidants are characterized by high specificity, strictly

Superoxide dismutase (SOD; KF 1.15.1.1.) Catalyzes the reduction reaction of

2·О2- + 2H+ → H2O2 + O2

In eukaryotic cells, SOD has several forms:

a) copper and zinc-containing SOD - localized in the cytosol, the

b) manganese-containing SOD - localized in the mitochondrial matrix

c) later, an iron-containing enzyme, found only in prokaryotes, was also detected;

Catalase (Cat .; EC 1.11.1.6) has the ability to decompose hydrogen

In both cases, the process goes through the formation of an intermediate

Cat. + Fe3 + + H2O2 K1 (set 1)

Compl. 1 + H2O2 K2 Cat. -Fe3 + + 2H2O + O2

Set 1 + AH2 k2Kat.-Fe3 + + 2H2O + A

An important role in maintaining the redox balance in the cell is played

Peroxiredoxins (thioredoxin peroxidases) is a widespread large family of

In mammals, for example, they control the level of cytokine-induced

Glutaredoxins are low molecular weight G-SH-dependent polyfunctional

Tocopherols are involved in the destruction of free radicals in cells and

Vitamin C is a synergist. Ascorbate restores tocopherol, turning into

Vitamin C participates in redox reactions, protecting hemoglobin from

cys and trans-retinal Retinoic acid

Flavonoids effectively neutralize radicals, due to the presence of hydroxyl

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