(2E)-4-Hydroxy-2-nonenal

Names

[ Name ]:
(2E)-4-Hydroxy-2-nonenal

[Synonym ]:
(2E)-4-Hydroxynon-2-enal
2-Nonenal, 4-hydroxy-, (E)-
4-hydroxy-trans-2-nonenal
4-hydroxy-2E-nonenal
4-hydroxy-2,3-trans-nonenal
4-hydroxy-2-nonena
4-hydroxynon-2-enal
MFCD00211020
2-Nonenal, 4-hydroxy-, (2E)-
(E)-4-hydroxynon-2-enal
4-hydroxynonenal
4-HYDROXY-2-NONENAL

Biological Activity

[Description]:

4-Hydroxynonenal (4-HNE) is an α,β unsaturated hydroxyalkenal and an oxidative/nitrosative stress biomarker. 4-Hydroxynonenal is a substrate and an inhibitor of acetaldehyde dehydrogenase 2 (ALDH2). 4-Hydroxynonenal can modulate a number of signaling processes mainly through forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and membrane lipids. 4-Hydroxynonenal plays an important role in cancer through mitochondria[1][2][3].

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Aldehyde Dehydrogenase (ALDH)

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Research Areas >> Neurological Disease

[Target]

Human Endogenous Metabolite

[In Vitro]

4-Hydroxynonenal is both a substrate and an inhibitor of ALDH2; inhibition of ALDH2 by 4-Hydroxynonenal is reversible at low concentration and become irreversible when the concentration of 4-HNE reaches 10 µM[1]. 4-Hydroxynonenal can induce antioxidant defense mechanisms to restrain its own production and to enhance the cellular protection against oxidative stress[1]. 4-Hydroxynonenal, the product of lipid peroxidation, is mutagenic and genotoxic in viruses, bacteria and mammalian cells. It reacts with all four DNA bases but with different efficiency: G >C > A >T. 4-Hydroxynonenal-dG represents the best biomarker of the genotoxic effects of 4-Hydroxynonenal and these adducts are primarily found in nuclear DNA. A classic example of etiological relevance of 4-Hydroxynonenal-dG in human cancers is 4-Hydroxynonenal-dG induced p53 mutation. 4-Hydroxynonenal-dG adducts were preferentially formed at the third base of codon 249 in the p53 gene, causing gene mutation and affecting diverse biological processes including cell cycle arrest, apoptosis, DNA repair, and differentiation[1].

[In Vivo]

Following 24 h after fluid percussion injury (FPI), the mouse brain tissue is analyzed for the expression level of NADPH oxidase 1 (NOX1), inducible nitric oxide synthase (iNOS), 4-Hydroxynonenal (4-HNE. Both wild-type (Nrf2+/+) and Nrf2-deficient mice (Nrf2−/−) results in increased expression of 4-Hydroxynonenal following 15 psi injury (moderate injury) when compared to uninjured Nrf2+/+ and Nrf2−/− mice. Similar to iNOS result, in Nrf2−/− KO mice, the expression level of 4-Hydroxynonenal is significantly high when compared to corresponding injured and uninjured Nrf2+/+ WT animals[2].

[References]

[1]. Zhong H, et al. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol. 2015;4:193-9.

[2]. Csala M, et al. On the role of 4-hydroxynonenal in health and disease. Biochim Biophys Acta. 2015 May;1852(5):826-38.

[3]. Bhowmick S, et al. Traumatic brain injury-induced downregulation of Nrf2 activates inflammatory response and apoptotic cell death. J Mol Med (Berl). 2019 Nov 22.

Chemical & Physical Properties

[ Density]:
0.9±0.1 g/cm3

[ Boiling Point ]:
275.6±23.0 °C at 760 mmHg

[ Molecular Formula ]:
C₉H₁₆O₂

[ Molecular Weight ]:
156.222

[ Flash Point ]:
115.2±15.2 °C

[ Exact Mass ]:
156.115036

[ PSA ]:
37.30000

[ LogP ]:
1.85

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.460

[ Storage condition ]:
-70°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RA8510000

CHEMICAL NAME :: 2-Nonenal, 4-hydroxy-

CAS REGISTRY NUMBER :: 75899-68-2

LAST UPDATED :: 199410

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C9-H16-O2

MOLECULAR WEIGHT :: 156.25

WISWESSER LINE NOTATION :: VH1U1YQ5

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 35 mg/kg

TOXIC EFFECTS :: Behavioral - fluid intake Blood - changes in cell count (unspecified) Nutritional and Gross Metabolic - metabolic acidosis

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 69 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Rodent - guinea pig Cells - not otherwise specified

DOSE/DURATION :: 100 umol/L

REFERENCE :: CBINA8 Chemico-Biological Interactions. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1969- Volume(issue)/page/year: 52,233,1984

Safety Information

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R36/37/38:Irritating to eyes, respiratory system and skin .

[ Safety Phrases ]:
S26-S37/39

[ HS Code ]:
2912491000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2912491000

[ Summary ]:
2912491000. other aldehyde-alcohols. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:5.5%. General tariff:30.0%