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(PROTEIN) WATER MOLECULE AMINO GROUP

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Figure 9–17<br />

Formation of free radicals and highly<br />

reactive oxygen compounds: superoxide<br />

(O 2 – or O-O ˜ ), hydroxyl radical (OH •˜ )<br />

and hypochlorus acid (HOCl ˜ ) by respiratory<br />

burst. ➤ These compounds<br />

readily donate their electrons to membrane<br />

lipids and proteins.<br />

2O2 (+ NADPH)<br />

oxygen<br />

NADP oxidase 2O2 - . (+ NADP + + H +)<br />

superoxide<br />

Fe<br />

H2O (+ 2 O )<br />

2<br />

hydrogen<br />

peroxide<br />

+2 (or Cu +1 )<br />

OH .<br />

hydroxyl<br />

OCl<br />

radical<br />

-<br />

* *<br />

myeloperoxidase<br />

*spontaneous,<br />

no enzyme used<br />

Ocular Immunochemistry • 265<br />

superoxide<br />

dismutase<br />

Cl -<br />

HOCl<br />

hypochlorous<br />

acid (biological<br />

"chlorox")<br />

1 O2 (+ H 2 O + Cl - )<br />

singlet<br />

oxygen<br />

The antigens become surrounded by the leucocyte membranes<br />

forming a phagosome (Greek: fagosoma- phagosoma—literally: a body<br />

for eating). The phagosome itself is internalized and fused with lysosomes<br />

(Greek lusosoma: literally: a body for breaking) where the antigenic<br />

particles or even whole bacteria or viruses are destroyed. Note that<br />

the fused bodies are this point are called phagolysosomes.<br />

The destruction of antigenic organisms begins in the phagosome<br />

with the formation of highly active forms of oxygen. This process is initiated<br />

with a respiratory burst in which leucocytes take up large quantities<br />

of oxygen (O 2) to form superoxide radicals (O 2 –• ). This is shown in<br />

Figure 9–17. Superoxide radicals have unpaired electrons that are highly<br />

reactive and unstable. The radicals are rapidly converted to other compounds<br />

(hydrogen peroxide, hydroxyl radicals, and singlet oxygen) that<br />

are themselves highly reactive with tissue proteins and membrane lipids.<br />

Some examples are shown in Figure 9–18.<br />

In the initial reaction of Figure 9–17, superoxide is dismuted or disproportioned<br />

(one molecule is reduced while the other is oxidized) to<br />

hydrogen peroxide by the enzyme superoxide dismutase. The need for<br />

the enzyme, in spite of the highly reactive species, has been shown to be<br />

necessary due to the relatively low concentrations of superoxide that are<br />

present (Babior, 2000). Some of the hydrogen peroxide is also converted<br />

to hypochlorous acid (commercially known as “chlorox”), a very highly<br />

reactive and destructive chemical for nearly any living organism (see<br />

Figure 9–17). All these oxidative species attack the membranes of the<br />

organism (see Figure 9–18) within the phagosome and then spill out into<br />

the surrounding cellular environment to cause collateral damage to<br />

nearby cells or even the phagocytes themselves eventually. The enzyme<br />

that catalyzes the formation of hypochlorous acid, myeloperoxidase, has<br />

a heme group at its active site that has a green color. The green color is<br />

the cause of the green hue that is associated with pus formation. Pus formation<br />

itself is the buildup of cellular debris from the oxidative destruction<br />

(described here) and enzymatic onslaught (described below) that has<br />

taken place.

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