Description
Docosa Hexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, sperm, testicles and retina. It can be synthesized from alphalinolenic acid or obtained directly from maternal milk or fish oil. DHA's structure is a carboxylic acid(~oic acid) with a 22-carbon chain (docosa- is Greek for 22) and six (Greek "hexa") cis double bonds (-en~); the first double bond is located at the third carbon from the omega end. Its trivial name is cervonic acid, its systematic name is all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid, and its shorthand name is 22:6(n-3) in the nomenclature of fatty acids.
Application
DHA is used as a supplement for premature babies and as an ingredient in baby formula during the first year of life to promote better mental development. It is also used in infant formula to prevent lung diseases, allergic diseases such as eczema or hay fever, and diarrhea. This practice probably started because DHA is found naturally in breast milk. In some cases, DHA is used in combination with arachidonic acid.
DHA is also taken by mouth alone or along with EPA to improve mental function in healthy people or those with mental impairment. It is also used to improve mental function in people with dementia or age-related mental decline. It is also taken by mouth for attention deficit-hyperactivity disorder (ADHD), depression, aggressive behavior, Alzheimer's disease, autism, and to prevent relapse in schizophrenic patients who stop taking antipsychotic medication.
DHA is also taken by mouth for diabetes, coronary artery disease (CAD), stroke, high levels of cholesterol and fats in the blood, high blood pressure, and cancer including breast and prostate cancer. It is also used for a type of fatty liver not related to drinking alcohol, obesity, ear infections, and learning problems in children.
Some people use DHA is for improving vision, preventing an eye disease called age-related macular degeneration (AMD), treating an eye condition called retinitis pigmentosa, and increasing DHA levels in people with cystic fibrosis.
DHA is taken by mouth in combination with eicosapentaenoic acid (EPA) for a variety of conditions, including the prevention and reversal of heart disease, stabilizing heart rhythm, preventing abnormal heart beats after heart surgery, painful menstrual periods, lupus, and certain kidney diseases. EPA and DHA are also used in combination for preventing migraine headaches in teenagers, Behcet's syndrome, psoriasis, Raynaud's syndrome, rheumatoid arthritis, bipolar disorder, and ulcerative colitis.
Biosynthesis of DHA
ALA is an essential fatty acid. It is synthesised in plants and in many lower organisms and is found in the human diet mainly as a component of green leaves, some nuts, seeds and vegetable oils, and foods made from or containing those ingredients. There is a metabolic pathway that links ALA to DHA. This pathway involves a series of enzyme-catalysed elongation and desaturation reactions. Elongation enzymes, called elongases, add pairs of carbon atoms to the growing acyl chain, in this case converting an 18-carbon fatty acid into a 22-carbon one, while desaturase enzymes insert double bonds into the acyl chain, in this case converting a fatty acid with 3 double bonds in its acyl chain into one with 6 double bonds. These reactions occur predominantly within the endoplasmic reticulum. The pathway is believed to mainly occur within the liver, but there is some evidence that other tissues, including brain and testis, have high expression of the genes encoding the relevant enzymes.
Description
Docosahexaenoic acid (DHA) is a long-chain ω-3 polyunsaturated fatty acid (PUFA) found in fish and algal oils. It comprises approximately 40% of total brain PUFAs and is abundant in grey matter and retinal membranes. DHA typically represents 0.52-7.5% of human total plasma fatty acids. It is produced from α-linolenic acid (ALA; Item Nos.
90210 |
21910)
via a series of desaturase- and elongase-catalyzed reactions, resulting in a docosapentaenoic acid (DPA; ) intermediate, which is elongated, desaturated, and β-oxidized to produce DHA. DHA can be liberated from cellular membranes by phospholipase A
2 (PLA
2) and converted to numerous oxylipins, including specialized pro-resolving mediators (SPMs), which are produced by lipoxygenases and include D-series protectins and resolvins, as well as maresins, that regulate host defense and the resolution of inflammation. DHA has roles in several physiological and pathological processes, including neural development, cardiovascular diseases, obesity, and inflammation.
DHA MaxSpec
® standard is a quantitative grade standard of DHA that has been prepared specifically for mass spectrometry and related applications where quantitative reproducibility is required. The solution has been prepared gravimetrically and is supplied in a deactivated glass ampule sealed under argon. The concentration was verified by comparison to an independently prepared calibration standard. The verified concentration is provided on the certificate of analysis. This DHA MaxSpec
® standard is guaranteed to meet identity, purity, stability, and concentration specifications and is provided with a batch-specific certificate of analysis. Ongoing stability testing is performed to ensure the concentration remains accurate throughout the shelf life of the product.
Note: The amount of solution added to the vial is in excess of the listed amount. Therefore, it is necessary to accurately measure volumes for preparation of calibration standards. Follow recommended storage and handling conditions to maintain product quality.
Chemical Properties
Clear Colourless Liquid
Occurrence
Ordinary types of cooked salmon contain 500 – 1500 mg DHA and 300–1000 mg EPA per 100 grams.(USDA) Additional top fish sources of DHA are: tuna, bluefish, mackerel, swordfish, anchovies, herring, sardines, and caviar.
The discovery of algae - based DHA In the early 1980s, NASA sponsored scientific research in search of a plant-based food source that could generate oxygen and nutrition on long-duration space flights. The researchers discovered that certain species of marine algae produced rich nutrients. This research led to the development of an algae-based, vegetable-like oil that contains two essential polyunsaturated fatty acids: DHA and ARA (Arachidonic acid).
Use as a food additive DHA is widely used as a food supplement. It was first used primarily in infant formulas. In 2004, the US Food and Drug Administration endorsed qualified health claims for DHA , and by 2007 DHA - fortified dairy items (milk, yogurt, cooking oil) started to appear in grocery stores.
DHA is believed to be helpful to people with a history of heart disease, for premature infants, and to support healthy brain development especially in young children along with supporting retinal development. Some manufactured DHA is a vegetarian product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega-3's such as EPA. Both fish oil and DHA are odorless and tasteless after processing as a food additive.
Studies of vegetarians and vegans
Vegetarian diets typically contain limited amounts of DHA, and vegan diets typically contain no DHA. Vegetarians and vegans have substantially lower levels of DHA in their bodies, and short-term supplemental ALA has been shown to increase EPA, but not DHA. However, supplemental preformed DHA, available in algae-derived oils or capsules, has been shown to increase DHA levels. While there is little evidence of adverse health or cognitive effects due to DHA deficiency in adult vegetarians or vegans, fetal and breast milk levels remain a concern.
DHA and EPA in fish oils Fish oil is widely sold in gelatin capsules containing a mixture of omega-3 fatty acids including EPA and smaller quantities of DHA. One study found fish oil higher in DHA than EPA lowered inflammatory cytokines, such as IL-6 and IL-1β, associated with neurodegenerative and autoimmune diseases. They note the brain normally contains DHA, but not EPA, though both DHA and EPA plasma concentrations increased significantly for participants.
Uses
Omega-3 fatty acid found in marine fish oils and in many phospholipids. Major structural component of excitable membranes of the retina and brain; synthesized in the liver from a-linolenic acid. Nutritional supplement.
Uses
Docosahexaenoic acid is found in fish oils in nature. It is also
commercially manufactured from microalgae; Crypthecodinium
cohnii and Schizochytrium.
Uses
Nutritional supplement.
Definition
ChEBI: A docosahexaenoic acid having six cis-double bonds at positions 4, 7, 10, 13, 16 and 19.
General Description
An omega-3 fatty acid essential for normal brain growth and
function, docosahexaenoic acid (DHA) plays an important role as a signaling factor in cells for both anti- and pro-inflammatory processes. Levels of docosahexaenoic acid as well as other fatty acids are analyzed by GC/MS or LC-MS/MS methods to monitor patients undergoing diet therapy for mitochondrial or peroxisomal disorders. This Certified Spiking Solution
is suitable for use as starting material in the
preparation of linearity standards, calibrators, or controls in mass spectrometry-based DHA testing applications such as assessment of cardiovascular disease risk and fatty acid deficiency, and detection and quantification of DHA in nutraceuticals and dietary supplements.
Biological Activity
Endogenous omega-3 fatty acid. Acts as a selective retinoid X receptor (RXR) agonist that displays no activity at RAR, thyroid hormone receptor or the vitamin D receptor (VDR). Activates all three RXR isoforms. Also shown to inhibit A β 1-42 fibrillation and toxicity in vitro .
Biochem/physiol Actions
Docosahexaenoic acid, DHA, is an omega-3 polyunsaturated fatty acid with 22 carbons and six double bonds, the first double bond occuring at position three from the methyl terminus (22:6 n-3). DHA is a component of lipid membranes and the myelin sheath. DHA also serves as a precursor for signaling molecules such as prostaglandins and eicosanoids.
Purification Methods
Its solubility in CHCl3 is 5%. It has been purified from fish oil by GLC using Ar as mobile phase and EGA as stationary phase with an ionisation detector [UV: Stoffel & Ahrens J Lipid Res 1 139 1959], and via the ester by evaporative "molecular" distillation using a 'continuous molecular still' at 10-4 mm with the highest temperature being 110o and a total contact time with the hot surface being 60sec [Farmer & van den Heuvel J Chem Soc 427 1938]. The methyl ester has b 208-211o/2mm, d4 0.9398, 20 1.5035. nD With Br2 it forms a dodecabromide m ca 240o(dec). Also, the acid was converted to the methyl ester and purified through a three-stage molecular still [as described by Sutton Chem Ind (London) 11383 1953] at 96o, and the rate was adjusted so that one-third of the material was removed each cycle of three distillations. The distillate (numbered 4) (13g) was dissolved in EtOH (100mL containing 8g of KOH) at -70o and set aside for 4hours at 30o with occasional shaking under a vacuum. Water (100mL) was added and the solution was extracted with pentane, washed with HCl, dried (MgSO4), filtered and evaporated to give a clear oil (11.5g) m -44.5o to -44.1o. In the catalytic hydrogenation of the oil six mols of H2 are absorbed and docosanoic acid (behenic acid) is produced with m 79.0-79.3o undepressed with an authentic sample (see docosanoic acid below) [Whitcutt Biochem J 67 60 1957]. [Beilstein 2 IV 1812.]
References
[1] CONNYE N. KURATKO Norman S Jr. Biomarkers of DHA status[J]. Prostaglandins, leukotrienes, and essential fatty acids, 2009, 81 2: Pages 111-118. DOI:
10.1016/j.plefa.2009.05.007[2] R.J.SCOTT LACOMBE Richard P B Raphal Chouinard Watkins. Brain docosahexaenoic acid uptake and metabolism[J]. Molecular Aspects of Medicine, 2018, 64: Pages 109-134. DOI:
10.1016/j.mam.2017.12.004[3] CALDER P. Docosahexaenoic Acid[J]. Annals of Nutrition and Metabolism, 2016, 306 1: 8-21. DOI:
10.1159/000448262[4] MARIA C. BASIL Bruce D L. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation[J]. Nature Reviews Immunology, 2015, 16 1: 51-67. DOI:
10.1038/nri.2015.4[5] ILSE A C ARNOLDUSSEN Amanda J K. Impact of DHA on metabolic diseases from womb to tomb.[J]. Marine Drugs, 2014, 12 12: 6190-6212. DOI:
10.3390/md12126190[6] YILONG ZOU. Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis[J]. Nature chemical biology, 2020, 16 3: 302-309. DOI:
10.1038/s41589-020-0472-6[7] DELPHINE LUMBROSO. Macrophage-Derived Protein S Facilitates Apoptotic Polymorphonuclear Cell Clearance by Resolution Phase Macrophages and Supports Their Reprogramming.[J]. Frontiers in Immunology, 2018: 358. DOI:
10.3389/fimmu.2018.00358[8] ANNE-SOPHIE ARCHAMBAULT. Comparison of eight 15-lipoxygenase (LO) inhibitors on the biosynthesis of 15-LO metabolites by human neutrophils and eosinophils.[J]. PLoS ONE, 2018: e0202424. DOI:
10.1371/journal.pone.0202424[9] BING-QING DENG. Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3β signaling.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017: 12608-12613. DOI:
10.1073/pnas.1705615114[10] JENNIFER MILDENBERGER. N-3 PUFAs induce inflammatory tolerance by formation of KEAP1-containing SQSTM1/p62-bodies and activation of NFE2L2.[J]. Autophagy, 2017, 13 10: 1664-1678. DOI:
10.1080/15548627.2017.1345411[11] SEUNG KYUN SHIN. Docosahexaenoic acid-mediated protein aggregates may reduce proteasome activity and delay myotube degradation during muscle atrophy in vitro[J]. Experimental and Molecular Medicine, 2017, 49 1: e287-e287. DOI:
10.1038/emm.2016.133[12] TSUYOSHI YAMAMOTO . Narrow-spectrum inhibitors targeting an alternative menaquinone biosynthetic pathway of Helicobacter pylori[J]. Journal of Infection and Chemotherapy, 2016, 22 9: Pages 587-592. DOI:
10.1016/j.jiac.2016.05.012[13] DANIèLE LUCAS. Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450.[J]. Journal of Lipid Research, 2010, 51 5: 1125-1133. DOI:
10.1194/jlr.m003061
