Simplified pathway for lipid autoxidation. The reaction is initiated by hydroxyl radical, which generates a pentadienyl radical (only one resonance structure shown). This radical adds O2 to give hydroperoxyl radical (red). In a propagation step, this hydroperoxyl radical abstracts an H atom from a new diene, generating a new pentadienyl radical and a hydroperoxide (blue).

Lipid peroxidation is the conversion of lipids to peroxide and hydroperoxide derivatives. These derivatives, known as lipid peroxides or lipid oxidation products (LOPs), are susceptible to further reactions that are relevant to "DNA and protein modification, radiation damage, aging..."[1] Lipid peroxidation mainly applies to unsaturated fats, especially polyunsaturated fats such as those derived from linoleic acid.


The conversion consists of three steps: initiation, propagation, and termination. In initiation, a free radical attacks the fatty acid chain. The nature of the free radical is unclear but described as reactive oxygen species (ROS). The breakdown of hydrogen peroxide by ferrous ions generates the OH· in the so-called Fenton reaction. Another ROS is HOO·. These radicals abstract a hydrogen atom from the fatty acid to make a fatty acid radical.[1]

In the propagation phase of the process, the fatty acid radical reacts readily with molecular oxygen, creating a peroxyl-fatty acid radical. This peroxyl radical can undergo a variety of reactions including the relocation of the O2 group, abstraction of H atoms on other fatty acids, or addition to another unsaturated fatty acid. These processes all produce new radicals, which is why the process is called a "radical chain reaction", which is an example of a chain reactions in living organisms. The radical reaction stops when two radicals are combined. Termination occurs when the concentration of radical species is high.

The generation of the initial radical is sensitive to kinetic isotope effect. Reinforced lipids, such as 11,11-D2-ethyl linoleate, suppress lipid peroxidation[2]

Role of antioxidants

Free radical mechanisms in tissue injury. Lipid peroxidation induced by xenobiotics and the subsequent detoxification by cellular enzymes (termination).

Lipid peroxidation is slowed by antioxidants, which neutralize free radicals by termination of radical chain reactions. Antioxidants include vitamin C and vitamin E[3] Other anti-oxidants include the enzymes superoxide dismutase, catalase, and peroxidase, which function by suppressing the availability of hydrogen peroxide, a common source of hydroxyl radical.

Medical implications

Phototherapy may cause lipid peroxidation leading to rupture of red blood cell cell membranes in this way.[4]

In addition, end-products of lipid peroxidation may be mutagenic and carcinogenic.[5] For instance, the end-product MDA reacts with deoxyadenosine and deoxyguanosine in DNA, forming DNA adducts to them, primarily M1G.[5]

Reactive aldehydes can also form Michael adducts or Schiff bases with thiol or amine groups in amino acid side chains. Thus, they are able to inactivate sensitive proteins through electrophilic stress.[6]

The toxicity of lipid hydroperoxides to animals is best illustrated by the lethal phenotype of glutathione peroxidase 4 (GPX4) knockout mice. These animals do not survive past embryonic day 8, indicating that the removal of lipid hydroperoxides is essential for mammalian life.[7]

On the other hand, it's unclear whether dietary lipid peroxides are bioavailable and play a role in disease, as a healthy human body has protective mechanisms in place against such hazards.[8]


Certain diagnostic tests are available for the quantification of the end-products of lipid peroxidation, to be specific, malondialdehyde (MDA).[5] The most commonly used test is called a TBARS Assay (thiobarbituric acid reactive substances assay). Thiobarbituric acid reacts with malondialdehyde to yield a fluorescent product. However, there are other sources of malondialdehyde, so this test is not completely specific for lipid peroxidation.[9]

See also


  1. ^ a b Porter, Ned A.; Caldwell, Sarah E.; Mills, Karen A. (1995). "Mechanisms of free radical oxidation of unsaturated lipids". Lipids. 30 (4): 277–290. doi:10.1007/BF02536034. PMID 7609594. S2CID 4051766.
  2. ^ Hill, S.; et al. (2012). "Small amounts of isotope-reinforced PUFAs suppress lipid autoxidation". Free Radical Biology & Medicine. 53 (4): 893–906. doi:10.1016/j.freeradbiomed.2012.06.004. PMC 3437768. PMID 22705367.
  3. ^ Huang, Han-Yao; Appel, Lawrence J.; Croft, Kevin D.; Miller, Edgar R.; Mori, Trevor A.; Puddey, Ian B. (September 2002). "Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial". The American Journal of Clinical Nutrition. 76 (3): 549–555. doi:10.1093/ajcn/76.3.549. ISSN 0002-9165. PMID 12197998.
  4. ^ Ostrea, Enrique M.; Cepeda, Eugene E.; Fleury, Cheryl A.; Balun, James E. (1985). "Red Cell Membrane Lipid Peroxidation and Hemolysis Secondary to Phototherapy". Acta Paediatrica. 74 (3): 378–381. doi:10.1111/j.1651-2227.1985.tb10987.x. PMID 4003061. S2CID 39547619.
  5. ^ a b c Marnett, LJ (March 1999). "Lipid peroxidation-DNA damage by malondialdehyde". Mutation Research. 424 (1–2): 83–95. doi:10.1016/s0027-5107(99)00010-x. PMID 10064852.
  6. ^ Bochkov, Valery N.; Oskolkova, Olga V.; Birukov, Konstantin G.; Levonen, Anna-Liisa; Binder, Christoph J.; Stockl, Johannes (2010). "Generation and Biological Activities of Oxidized Phospholipids". Antioxidants & Redox Signaling. 12 (8): 1009–1059. doi:10.1089/ars.2009.2597. PMC 3121779. PMID 19686040.
  7. ^ Muller, F. L., Lustgarten, M. S., Jang, Y., Richardson, A. and Van Remmen, H. (2007). "Trends in oxidative aging theories". Free Radical Biology and Medicine. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558.((cite journal)): CS1 maint: multiple names: authors list (link)
  8. ^ Vieira, Samantha A.; Zhang, Guodong; Decker, Eric A. (2017). "Biological Implications of Lipid Oxidation Products". Journal of the American Oil Chemists' Society. 94 (3): 339–351. doi:10.1007/s11746-017-2958-2. S2CID 90319530.
  9. ^ Trevisan, M.; Browne, R; Ram, M; Muti, P; Freudenheim, J; Carosella, A. M.; Armstrong, D (2001). "Correlates of Markers of Oxidative Status in the General Population". American Journal of Epidemiology. 154 (4): 348–56. doi:10.1093/aje/154.4.348. PMID 11495858.