20-Hydroxyeicosa-5Z,8Z,11Z,14Z-tetraenoic acid
[CAS# 79551-86-3]

Identification

• Classification: Analytical chemistry >> Food safety >> Fatty acid, fatty acid methyl ester
• Name: 20-Hydroxyeicosa-5Z,8Z,11Z,14Z-tetraenoic acid
• Synonyms: omega-Hydroxyarachidonic acid
• Molecular Formula: C₂₀H₃₂O₃
• Molecular Weight: 320.47
• CAS Registry Number: 79551-86-3
• SMILES: C(CC/C=CC/C=CC/C=CC/C=CCCCC(=O)O)CCO

Properties

• Solubility: Practically insoluble in water) (0.061 g/L) (25 °C), Calc.^*, DMSO: 45mg/mL (Expl.)
• Density: 0.985±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 482.0±33.0 °C 760 mmHg (Calc.)^*
• Flash point: 259.4±21.9 °C (Calc.)^*
• Index of refraction: 1.515 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• Risk Statements: H225-H319
• Safety Statements: P210-P233-P240-P241-P242-P305+P351+P338

Discovery and Applications

20-Hydroxyeicosa-5Z,8Z,11Z,14Z-tetraenoic acid, commonly known as 20-HETE, is a biologically active metabolite derived from arachidonic acid, a 20-carbon polyunsaturated fatty acid. It belongs to the family of hydroxyeicosatetraenoic acids, which are oxygenated derivatives produced primarily through the action of cytochrome P450 enzymes.

The discovery of 20-HETE emerged from studies on arachidonic acid metabolism in the late 20th century, as researchers sought to understand the diverse roles of eicosanoids in physiological and pathological processes. 20-HETE is generated mainly by the ω-hydroxylation of arachidonic acid at the 20th carbon position by specific cytochrome P450 isoforms, particularly those in the CYP4A and CYP4F subfamilies.

This metabolite is known to act as a potent signaling molecule involved in the regulation of vascular tone, renal function, and inflammatory responses. In the vascular system, 20-HETE functions as a vasoconstrictor by modulating ion channels and signaling pathways in vascular smooth muscle cells, thus contributing to the regulation of blood pressure and blood flow.

In the kidney, 20-HETE influences sodium transport and tubular function, playing a role in the control of sodium balance and fluid homeostasis. Its actions affect the modulation of renal vascular resistance and glomerular filtration rate, linking it to mechanisms involved in hypertension and kidney disease.

Beyond its vascular and renal effects, 20-HETE has been implicated in the modulation of inflammation and cellular proliferation. It participates in signaling cascades that influence the behavior of endothelial cells and immune cells, thereby contributing to responses to injury and disease.

Clinically, alterations in 20-HETE levels or metabolism have been associated with various pathological conditions, including hypertension, stroke, cancer, and metabolic disorders. Its role as a mediator in these diseases has made it a target of interest for therapeutic intervention and biomarker development.

Research into 20-HETE continues to explore its complex physiological roles and potential as a pharmacological target. Inhibitors or modulators of its biosynthesis and action are being studied for their capacity to treat cardiovascular and renal diseases, among other conditions.

In summary, 20-Hydroxyeicosa-5Z,8Z,11Z,14Z-tetraenoic acid is a cytochrome P450-derived metabolite of arachidonic acid with significant functions in vascular regulation, kidney function, and inflammation. Its discovery has expanded the understanding of eicosanoid biology and opened avenues for therapeutic exploration in related diseases.

References

1989. Vasoactivity of 20-hydroxyeicosatetraenoic acid is dependent on metabolism by cyclooxygenase. The Journal of Pharmacology and Experimental Therapeutics, 248(1).
DOI: 10.1016/s0022-3565(25)23636-9

2022. Neutrophil-Derived Myeloperoxidase and Hypochlorous Acid Critically Contribute to 20-Hydroxyeicosatetraenoic Acid Increases that Drive Postischemic Angiogenesis. The Journal of Pharmacology and Experimental Therapeutics, 381(3).
DOI: 10.1124/jpet.121.001036

2024. 20-HETE and Hypertension. Hypertension, 81(9).
DOI: 10.1161/hypertensionaha.124.21718