Lipid Peroxidation Is A Source Of Free Radicals

Peroxidation (auto-oxidation) of lipids exposed to oxygen is responsible not only for deterioration of foods (rancidity) but also for damage to tissues in vivo, where it may be a cause of cancer, inflammatory diseases, atherosclerosis, and aging. The deleterious effects are considered to be caused by free radicals (ROO^, RO^, OH^) produced during peroxide formation from fatty acids containing methylene-interrupted double bonds, ie, those found in the naturally occurring polyunsaturated fatty acids (Figure 14-21). Lipid peroxidation is a chain reaction providing a continuous supply of free radicals that initiate further peroxidation. The whole process can be depicted as follows:

(1) Initiation:

ROOH + Metal(n)+ ^ ROO^ + Metal(n-1)+ + H+ + RH ^ R^+ XH

(2) Propagation:


Figure 14-16. Generalized steroid nucleus, showing (A) an a\\-trans configuration between adjacent rings and (B) a cis configuration between rings A and B.

Figure 14-17. Cholesterol, 3-hydroxy-5,6-cholestene.

Figure 14-17. Cholesterol, 3-hydroxy-5,6-cholestene.

(3) Termination:

— CH = C — CH = CH — Figure 14-19. Isoprene unit.

Peroxidation is also catalyzed in vivo by heme compounds and by lipoxygenases found in platelets and leukocytes. Other products of auto-oxidation or en-zymic oxidation of physiologic significance include oxysterols (formed from cholesterol) and isoprostanes (prostanoids).

ROO^ + ROO^ ^ ROOR + O2 ROO^ + R^ ^ ROOR R^ + R^ ^ RR

Since the molecular precursor for the initiation process is generally the hydroperoxide product ROOH, lipid peroxidation is a chain reaction with potentially devastating effects. To control and reduce lipid peroxidation, both humans in their activities and nature invoke the use of antioxidants. Propyl gallate, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) are antioxidants used as food additives. Naturally occurring antioxidants include vitamin E (tocopherol), which is lipid-soluble, and urate and vitamin C, which are water-soluble. Beta-carotene is an antioxidant at low Po2. Antioxidants fall into two classes: (1) preventive antioxidants, which reduce the rate of chain initiation; and (2) chain-breaking antioxidants, which interfere with chain propagation. Preventive antioxidants include catalase and other peroxidases that react with ROOH and chelators of metal ions such as EDTA (ethylenediaminetetraacetate) and DTPA (diethylene-triaminepentaacetate). In vivo, the principal chain-breaking antioxidants are superoxide dismutase, which acts in the aqueous phase to trap superoxide free radicals (O2t); perhaps urate; and vitamin E, which acts in the lipid phase to trap ROO^ radicals (Figure 45-6).

Figure 14-18. Ergosterol.
Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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