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Bioenergetics > Free radicals > Flashcards

Free radicals Flashcards

1
Q

We need O2 for…?

-give examples (3)

A
  • ATP generation
  • Detoxification
  • Biosynthesis
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2
Q

What can highly reactive oxygen radicals cause? (2)

A
  • damage to cellular lipids, proteins and DNA

- cellular death and degeneration

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3
Q

Free radical

-definition

A
  • particles with an unpaired electron spinning around the nucleus
  • tends to reach equilibrium, plucks an electrons from the nearest molecule
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4
Q

Radical nature of O

A
  • biradical

- two single electrons in different orbitals

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5
Q

ROS (reactive oxygen species)

  • free radicals - saskia harms paula and heiko (5)
  • not free radicals (4)
A
  • superoxide, hydroperoxyl, peroxyl, alkoxyl and hydroxyl radical
  • hydrogen peroxide, ozone, singlet oxygen, hypochlorous acid
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6
Q

Example of free radicals (3)

A
  • Oxidative phosphorylation, when the electrons are transferred to oxygen by cytochrome C oxidase.
  • Normally O2 accepts 4e- and becomes water
  • Free radicals occur when it does not accept 4 but less than that, ex: superoxide, accepts only 1e-. hydroxyl radical accepts only 3e-
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7
Q

Hydroxyl radical OH (2)

A
  • most potent

- initiates chain reactions that froms lipid peroxides and organic radicals and adds directly to compounds

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8
Q

Superoxide anion (3)

A
  • highly reactive
  • limited lipid solubility and cannot diffuse far
  • can generate hydroxyl and hydroperoxyl radicals
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9
Q

Hydrogen peroxide (3)

A
  • not actually a radical, but it can generate the hydroxyl radical
  • lipid soluble
  • at localized Fe2+ or Cu+ sites (ex: mitochondria) is also the precursor of hypochlorous acid
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10
Q

RNOS (reactive nitrogen oxygen species

  • free radicals (2)
  • not free radicals (5)
A
  • nitrogen (II) oxide, nitrogen (IV) oxide

- nitrosyl, nitrous acid, nitrogen (III) oxide, peroxynitrite, alkylperoxinitrite

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11
Q

ROS may be generated: (3)

A
  • enzymatically
  • non- enzmatically
  • membranes enzymes and/ or coenzymes with flavine structures, enzymes containing Cu atom in an active site
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12
Q

How can CoQ generates superoxide?

A

The one- electron reduced form of CoQ is free within the membrane and can accidentally transfer an electron to dissolved O2, forming superoxide

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13
Q

Main sources of free radicals (2)

A
  • oxidases, peroxidades, oxygenase in the cell bind O2 and transfer single electrons via a metal
  • Cytochrome P450 enzymes are a major source of free radicals
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14
Q

Ionizing radiation

-how does it cause damage to the body?

A

It has a high enough energy level that it can split water into the hydroxyl and hydrogen radicals, thus leading to radiation damage to the skin, mutation, cancer and cell death

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15
Q

Radical chain reaction mechanism

A
  1. Initiation: produce a chain carrying radical
  2. Propagation: chain continues to grow
  3. Degradation
  4. Termination: if the chain carrying molecule combines with another radical, there are no other radicals to propagate the reaction
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16
Q

Oxidative damage to lipids

  • damage
  • sequel
A
  • unsaturated bonds loss

- changes in fluidity and permeability of membranes

17
Q

Oxidative damage to proteins

  • damage
  • sequel
A
  • fragmentation and cleavage, functional group modification

- changes in: enzymes activity, ions transport, proteolysis

18
Q

Amino acids which are susceptible to hydroxyl radical attack and oxidative damage (5)

A
  • proline
  • histidine
  • arginine
  • cysteine
  • methionine
19
Q

Oxidative damage to DNA

  • damage
  • sequel
A
  • bases modification, chain breakage

- mutation, translational mistakes

20
Q

Respiratory burst (2)

A
  • phagocytic cells of the immune system exhibit a rapid consumption of O2
  • part of the antimicrobial defense system, it is intended to destroy invading microorganisms, tumor cells, etc.
21
Q

Production of ROS during the respiratory burst

-steps (6)

A
  1. Activation of NADPH oxidase initiates it with the generation of superoxide
  2. Superoxide (enzymatically or spontaneously) generates H2O2
  3. Myeloperoxidase generates HOCL
  4. H2O2 can generate hydroxyl radical from the Fenton reaction
  5. Inducible nitric oxide synthase may be activated and generate NO
  6. Nitric oxide + superoxide forms peroxynitrite, it may generate addtional RNOS
22
Q

Antioxidant defense system

A

Can eliminate free radicals by donating electrons
3 levels:
1. Inhibition of production of ROS
2. Capture of radicals (scavengers, trappers)
3. Correction mechanism of destroyed biomolecules

23
Q

Endogenous antioxidants

  • enzymes
  • non- enzymatic
A

Enzymes: cytochrome c, catalase

Non- enzymatic: fixed in membranes (a- tocopherol, B- caroten), out of membranes (ascorbate, transferrin)

24
Q

Exogenous antioxidants (3)

A
  • FR scavengers
  • Trace elements
  • Drugs and compounds influence to FR metabolism
25
Q

Enzymatic defense against ROS includes: (3)

A
  • Superoxide dismutase
  • Catalase
  • Glutathione peroxidase
26
Q

Superoxide dismutase

A
  • present in all oxygen- metabolizing cells
  • inducible in case of superoxide overproduction

3 isoenzymes forms:
Cu+ - Zn2+ present in the cytosol
Mn2+ present in mitochondria
Cu+ - Zn2+ found extracellulary

27
Q

Catalase (3)

A
  • capable of reducing hydrogen peroxide to water and oxygen
  • high affinity to H2O2- cytoplasm of erythrocytes
  • tetramer with Fe, need NADPH
28
Q

Glutathion (3)

A
  • principal means of protecting against oxidative damage
  • tripeptide
  • glutamate, cysteine, glycine
29
Q

Glutathion peroxidases (4)

A
  • family of selenium enzymes
  • in the cytosol and mitochondria
  • major means of removing H2O2 produced outside of peroxisomes
  • it also oxidizes 2 GSH, turning it into GSSG
30
Q

Glutathione Reductase (3)

A
  • catalyzes transfer of electrons from NADPH
  • major source is pentose phosphate pathway
  • turn oxidized glutathione back into its normal form (2 GSH)
31
Q

Non- enzymatic antioxidants = free radical scavengers

A

They convert free radicals to a non-radical nontoxic form in non- enzymatic reactions

32
Q

Antioxidants

-definitions

A

Compounds that neutralize free radicals by donating a hydrogen atom (with its one electron) to the radical

33
Q

Sources of antioxidants

A

Dietary - vitamin E, vitamin C, carotenoids

Endogenously produced - urate and melatonin

34
Q

Vitamin E (3)

A
  • a- tocopherol
  • lipid- soluble antioxidant vitamin
  • protect against lipid peroxidation in membranes
35
Q

Vitamin C (5)

MEMORIZE THIS!!!!!!!!!!!

A
  • ascorbic acid
  • it is an oxidation- reduction coenzyme
  • plays a role in free radical defense
  • reduced ascorbate can regenerate the reduced form of vitamin E through donating electrons in a redox cycle
  • it is water- soluble and circulates unbound in blood and extracellular fluid, where it has access to the lipid- soluble vitamin
36
Q

Oxidative stress

A

Equilibrium failure between creation and elimination of RNOS leads to oxidative stress

(imbalance between free radicals and antioxidants in your body)

37
Q

Oxidative stree markers:

  1. Lipoperoxidation markers
  2. Oxidative damage to protein markers
  3. Oxidative damage to DNA
A
  1. conjudated diens, isoprostanes
  2. protein hydroperoxides
  3. modified nucleosides
38
Q

Diseases associated with free radical injury

A

Diabetes
Acute renal failure
Alcohol induce liver disease
Aging

Bioenergetics (4 decks)

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