S-Nitrosothiol
Encyclopedia
S-Nitrosothiols, also known as thionitrites, are organic compound
s or functional group
s containing a nitroso
group attached to the sulfur
atom of a thiol
. S-Nitrosothiols have the general formula RS
N
O
, where R denotes an organic group.
S-Nitrosothiols have received much attention in biochemistry
because they serve as donors of the nitrosonium
ion NO+, and nitric oxide
and some organic nitroso derivatives serve as signaling molecules in living systems, especially related to vasodilation
. Red blood cell
s, for instance, release S-nitrosothiols into the bloodstream under low-oxygen conditions, causing the blood vessels to dilate.
The addition of a nitroso group to a sulfur atom of an amino acid
residue of some protein is known as S-nitrosation or S-nitrosylation. This is a reversible process and a major form of posttranslational modification
of proteins.
S-Nitrosated proteins (SNOs) serve to transmit nitric oxide
(NO) bioactivity and to regulate protein function through mechanisms analogous to phosphorylation: NO donors target specific amino acids motifs; post-translational modification leads to changes in protein activity, protein interactions, or subcellular location of target proteins; all major classes of proteins can undergo S-nitrosylation; and enzymes play a primary role in regulation of S-nitrosylation. Nitric oxide synthase
(NOS) activity leads directly to SNO formation. NOSs are hemoproteins that combine reductase and oxygenase catalytic domains in one monomer to synthesize NO from the terminal nitrogen atom of L-arginine in the presence of NADPH and O2. NOSs target specific Cys residues for S-nitrosylation. Thiol S-nitrosylation and NO transfer reactions (transnitrosation reactions) are involved in virtually all classes of cell signaling, ranging from regulation of ion channels and G-protein coupled reactions to receptor stimulation and activation of nuclear regulatory protein.
of electrons.
S-Nitrosothiols arise from condensation
from nitrous acid
and a thiol:
Many other methods exist for their synthesis. They can be synthesized from thiols using NaNO2
/H+, N2O3, N2O4, HNO
, NOCl, RONO
, NO2
, HNO2, bovine aortic
endothelial cells, among others. NaNO2/H+ and tert-butyl nitrite (tBuONO) are commonly used.
Once formed, these deeply colored compounds are often thermally unstable with respect to formation of the disulfide
and nitric oxide:
S-Nitrosothiols release NO+
upon treatment with acids:
and they can transfer nitroso groups to other thiol
s:
.
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
s or functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s containing a nitroso
Nitroso
Nitroso refers to a functional group in organic chemistry which has the general formula RNO. Nitroso compounds are a class of organic compounds containing the nitroso functional group, R−N=O....
group attached to the sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
atom of a thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
. S-Nitrosothiols have the general formula RS
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
O
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
, where R denotes an organic group.
S-Nitrosothiols have received much attention in biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
because they serve as donors of the nitrosonium
Nitrosonium
The nitrosonium ion is NO+, in which the nitrogen atom is bonded to an oxygen atom with a bond order of 3, and the overall diatomic species bears a positive charge. This ion is usually obtained as the following salts: NOClO4, NOSO4H , and NOBF4. The ClO and BF salts are slightly soluble in CH3CN...
ion NO+, and nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
and some organic nitroso derivatives serve as signaling molecules in living systems, especially related to vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
. Red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s, for instance, release S-nitrosothiols into the bloodstream under low-oxygen conditions, causing the blood vessels to dilate.
The addition of a nitroso group to a sulfur atom of an amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residue of some protein is known as S-nitrosation or S-nitrosylation. This is a reversible process and a major form of posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
of proteins.
S-Nitrosated proteins (SNOs) serve to transmit nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
(NO) bioactivity and to regulate protein function through mechanisms analogous to phosphorylation: NO donors target specific amino acids motifs; post-translational modification leads to changes in protein activity, protein interactions, or subcellular location of target proteins; all major classes of proteins can undergo S-nitrosylation; and enzymes play a primary role in regulation of S-nitrosylation. Nitric oxide synthase
Nitric oxide synthase
Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes...
(NOS) activity leads directly to SNO formation. NOSs are hemoproteins that combine reductase and oxygenase catalytic domains in one monomer to synthesize NO from the terminal nitrogen atom of L-arginine in the presence of NADPH and O2. NOSs target specific Cys residues for S-nitrosylation. Thiol S-nitrosylation and NO transfer reactions (transnitrosation reactions) are involved in virtually all classes of cell signaling, ranging from regulation of ion channels and G-protein coupled reactions to receptor stimulation and activation of nuclear regulatory protein.
Structure and reactions
The prefix "S" indicates that the NO group is attached to sulfur. The S-N-O angle deviates strongly from 180° because the nitrogen atom bears a lone pairLone pair
In chemistry, a lone pair is a valence electron pair without bonding or sharing with other atoms. They are found in the outermost electron shell of an atom, so lone pairs are a subset of a molecule's valence electrons...
of electrons.
S-Nitrosothiols arise from condensation
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...
from nitrous acid
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
and a thiol:
- RSH + HONO → RSNO + H2O
Many other methods exist for their synthesis. They can be synthesized from thiols using NaNO2
Sodium nitrite
Sodium nitrite is the inorganic compound with the chemical formula NaNO2. It is a white to slight yellowish crystalline powder that is very soluble in water and is hygroscopic...
/H+, N2O3, N2O4, HNO
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
, NOCl, RONO
Alkyl nitrites
Alkyl nitrites are a group of chemical compounds based upon the molecular structure R-ONO. Formally they are alkyl esters of nitrous acid. They are distinct from nitro compounds ....
, NO2
Nitrogen dioxide
Nitrogen dioxide is the chemical compound with the formula it is one of several nitrogen oxides. is an intermediate in the industrial synthesis of nitric acid, millions of tons of which are produced each year. This reddish-brown toxic gas has a characteristic sharp, biting odor and is a prominent...
, HNO2, bovine aortic
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
endothelial cells, among others. NaNO2/H+ and tert-butyl nitrite (tBuONO) are commonly used.
Once formed, these deeply colored compounds are often thermally unstable with respect to formation of the disulfide
Disulfide
In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....
and nitric oxide:
- 2 RSNO → RSSR + 2 NO
S-Nitrosothiols release NO+
Nitrosonium
The nitrosonium ion is NO+, in which the nitrogen atom is bonded to an oxygen atom with a bond order of 3, and the overall diatomic species bears a positive charge. This ion is usually obtained as the following salts: NOClO4, NOSO4H , and NOBF4. The ClO and BF salts are slightly soluble in CH3CN...
upon treatment with acids:
- RSNO + H+ → RSH + NO+
and they can transfer nitroso groups to other thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
s:
- RSNO + R'SH → RSH + R'SNO
Detection
S-Nitrosothiols can be detected with UV-vis spectroscopyUltraviolet-visible spectroscopy
Ultraviolet-visible spectroscopy or ultraviolet-visible spectrophotometry refers to absorption spectroscopy or reflectance spectroscopy in the ultraviolet-visible spectral region. This means it uses light in the visible and adjacent ranges...
.
Examples
- S-NitrosoglutathioneS-NitrosoglutathioneS-Nitrosoglutathione is an endogenous S-nitrosothiol that plays a critical role in nitric oxide signaling and is a source of bioavailable NO. NO coexists in cells with SNOs that serve as endogenous NO carriers and donors...
(GSNO) - S-Nitroso-N-acetylpenicillamineS-Nitroso-N-acetylpenicillamineS-Nitroso-N-acetylpenicillamine is the chemical compound with the formula ONSC2CHCO2H. SNAP is an S-nitrosothiol and is used as a model for the general class of S-nitrosothiols which have received much attention in biochemistry because nitric oxide and some organic nitroso derivatives serve as...
(SNAP)