Oxidation of Amino Acids, Peptides, and Proteins

Kinetics and Mechanism

Virender K. Sharma, Steven E. Rokita

• Publisher: Wiley
• Year: 2012
• Print ISBN: 9780470627761
• eBook ISBN: 9781118482452
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

Explains the role of reactive intermediates in biological systems as well as in environmental remediation

With its clear and systematic approach, this book examined the broad range of reactive intermediate that can be generated in biological environments, detailing the fundamental properties of each reactive intermediate. Readers gain a contemporary understanding of how these intermediates react with different compounds, with an emphasis on amino acids, peptides, and proteins. The author not only sets forth the basic chemistry and nature of reactive intermediates, he also demonstrates how the properties of the intermediates presented in the book compare with each other.

Oxidation of Amino Acids, Peptides, and Proteins begins with a discussion of radical and non-radical reactive species as well as an exploration of the significance of reactive species in the atmosphere, disinfection processes, and environmental remediation. Next, the book covers such topics as:

• Thermodynamics of amino acids and reactive species and the effect of metal-ligand binding in oxidation chemistry
• Kinetics and mechanisms of reactive halogen, oxygen, nitrogen, carbon, sulfur and phosphate species as well as reactive high-valent Cr, Mn, and Fe species
• Reactivity of the species with molecules of biological and environmental importance
• Generation of reactive species in the laboratory for kinetics studies
• Oxidation of amino acids, peptides, and proteins by permanganate, ferryl, and ferrate species
• Application of reactive species in purifying water and treating wastewater

With this book as their guide, readers will be able to assess the overall effects of reactive intermediates in biological environments. Moreover, they'll learn how to apply this knowledge for successful water purification and wastewater treatment.

1

REACTIVE SPECIES

Reactive intermediates and oxidative damage of proteins are important in biomedical research due to their roles in pathologies and aging [1–5]. Reactive species are also associated with important mediators in a wide range of biological processes such as signaling, for proper synaptic plasticity, and normal memory [3, 6–9]. Additionally, nitroxidative species contribute to pain and central sensitization [10, 11]. The amounts of reactive species during neurodegenerative diseases and aging increase to higher levels than the antioxidants present in a cell can handle. The reactive species that participate in a large number of reactions in diseases [4, 12–17] include both free radicals and nonradical species (Table 1.1) [18–20]. Reactive oxygen species (ROS) include superoxide anion (

), hydroperoxyl (

), alkoxyl (RO^•), peroxyl (ROO^•), hydroxyl radical (^•OH), hydrogen peroxide (H₂O₂), ozone (O₃), singlet oxygen (¹O₂), and hypochlorous acid (HOCl). The ROS initiate many reactions, for example, the primary mitochondrial ROS,

, reacts with superoxide dismutase (SOD) to form H₂O₂, which then reacts further with metal ions or their complexes (Fenton and Fenton-like reactions) to produce ^•OH. Other intermediates are reactive nitrogen species (RNS), which include nitric oxide (NO^•), nitrogen dioxide radical (

), peroxynitrite (OONO⁻), peroxynitrous acid (OONOH), alkylperoxynitrite (ROONO), and nitrosyl (NO⁺).

TABLE 1.1. Various Reactive Species

Adapted from Halliwell [18] with the permission of the International Society of Neurochemistry.

Free Radicals	Nonradicals
Reactive oxygen species (ROS)
Superoxide,	Hydrogen peroxide, H2O2
Hydroxyl, ^•OH	Hypobromous acid, HOBr^a
Hydroperoxyl, (protonated superoxide)	Hypochlorous acid, HOCl^b
Carbonate,	Ozone, O3 ^c
Peroxyl,	Singlet
Alkoxyl, RO^•	Organic peroxides, ROOH
Carbon dioxide radical,	Peroxynitrite, ONOO^− ^d
Singlet	Peroxynitrate, O2NOO^− ^d
	Peroxynitrous acid, ONOOH _
	Peroxomonocarbonate,
	Nitrosoperoxycarbonate, ONOOCO2
Reactive nitrogen species (RNS)
Nitric oxide, NO^•	Nitrous acid, HNO2
Nitrogen dioxide, NO2 ^c	Nitrosyl cation, NO^+
Nitrate,	Nitroxyl anion, NO^−
	Dinitrogen tetroxide, N2O4
	Dinitrogen trioxide, N2O3
	Peroxynitrite, ONOO^− ^d
	Peroxynitrate, O2NOO^−
	Peroxynitrous acid, ONOOH^d
	Nitronium cation,
	Alkyl peroxynitrites, ROONO
	Alkyl peroxynitrates, RO2ONO
	Nitryl chloride, NO2Cl
	Peroxyacetyl nitrate, ^c
Reactive chlorine species (RCS)
Atomic chlorine, Cl^•	Hypochlorous acid, HOCl^b
	Nitryl chloride, NO2Cl^e
	Chloramines
	Chlorine gas (Cl2)
	Bromine chloride (BrCl)^a
	Chlorine dioxide (ClO2)
Reactive bromine species (RBS)
Atomic bromine, Br^•	Hypobromous acid (HOBr)
	Bromine gas (Br2)
	Bromine chloride (BrCl)

“ROS” is a collective term that includes both oxygen radicals and certain nonradicals that are oxidizing agents and/or are easily converted into radicals (HOCl, HOBr, O₃, ONOO⁻, ¹O₂, H₂O₂).

All oxygen radicals are ROS, but not all ROS are oxygen radicals. Peroxynitrite and H₂O₂ are frequently erroneously described in the literature as free radicals, for example. “RNS” is a similar collective term that includes NO and NO₂ as well as nonradicals such as HNO₂ and N₂O₄.

“Reactive” is not always an appropriate term: H₂O₂, NO^•, and

react fast with few molecules, whereas ^•OH reacts fast with almost everything. Species such as

,

, RO^•, HOCl, HOBr,

,

,

, ONOO⁻,

, and O₃ have intermediate reactivities.

^a HOBr and BrCl could also be regarded as RBS.

^b HOCl and HOBr are often included as ROS, although HOCl is also an RCS.

^c Oxidizing species formed in polluted air that are toxic to plants and animals.

is also produced in vivo by myeloperoxidase and from ONOO⁻ [19]. Ozone might also be produced in vivo, although the chemistry involved is unclear [20].

^d ONOO⁻, O₂NOO⁻, and ONOOH are often included as ROS but are also classifiable as RNS.

^e NO₂Cl can also be regarded as a RNS.

ROS and RNS are interconnected and cause protein damage in biological processes.

, NO^•, and ONOO⁻ are associated with neuroimmune activation, supraspinal descending facilitation, and nitroxidative stress [21]. The

species is produced from mitochondria and NADPH oxidase, while NOS enzymes synthesize NO^• through enhanced nociception and the activation of the N-methyl-D-aspartate receptor. Both

and NO^• form ONOO⁻, which inactivates the glutamate transporter, manganese superoxide dismutase (MnSOD), and glutamate synthase, which increases the production of additional nitroxidative species [10]. In addition to ROS and RNS, other reactive species also involved in various biological activities include the carbonate radical (

) and the organic radical, R^• (thiyl and protein radicals). Metals such as Cr, Mn, and Fe in their high-valent sates are also involved in reactions with molecules of biological importance. Reactive intermediates may also be produced by UV radiation in the presence of oxygen [22].

1.1 DISEASES

1.1.1 Neurodegenerative Diseases

Generally, there are four common features in neurodegenerative diseases, which are interrelated with one another [23–25]. These include (1) both ROS and RNS working together to cause damage in the degenerative disease and also to create a vicious cycle by stimulating proinflammatory gene transcription in glia; (2) participation of redox-active (e.g., Cu and Fe) and redox-inactive (e.g., Zn) metal ions; (3) abnormal functioning of mitochondria; and (4) accumulation of misfolded or unfolded proteins in brain cells, which leads to Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), frontotemporal labor degeneration (FTLD), multiple sclerosis, and amyotrophic lateral sclerosis (ALS) (Table 1.2) [26]. A recent study demonstrated the role of RNS in protein misfolding, mitochondrial dysfunction, and synaptic injury [27]. Most of the folded proteins display toxicity toward cultured neuronal cells in vitro and, hence, may be related to the degeneration and loss of nerve cells in vivo. The molecular mechanism of toxic effect...

Table of contents

• COVER
• WILEY SERIES OF REACTIVE INTERMEDIATES IN CHEMISTRY AND BIOLOGY
• TITLE PAGE
• COPYRIGHT PAGE
• DEDICATION
• PREFACE TO SERIES
• INTRODUCTION
• 1 REACTIVE SPECIES
• 2 ACID–BASE PROPERTIES
• 3 HALOGENATED SPECIES
• 4 REACTIVE OXYGEN SPECIES
• 5 REACTIVE INORGANIC OXY-SPECIES OF C, N, S, AND P
• 6 HIGH-VALENT Cr, Mn, AND Fe SPECIES
• INDEX