FIGURE 19.3. Xanthine Oxidase (XO) pathway activation by ischaemia-reperfusion and the production of reactive oxygen species. Ischaemia prevents oxidative phosphorylation (1) and cellular ATP cannot be regenerated. This leads to the accumulation of AMP and, in turn, hypoxanthine. Ischaemia also causes the accumulation of intracellular calcium (2). This catalyses the conversion of xanthine dehydrogenase (XD) to xanthine oxidase (XO) Upon reperfusion oxygen is supplied (3) and this provides the final substrate to allow XO to convert hypoxanthine to xanthine, producing superoxide as a by-product (4). During ischaemia iron is released from cytochrome, haemoglobin and other haem containing molecules (5). This iron catalyses the Fenton-Haber-Weiss reaction producing hydroxyl radicals from superoxide. These hydroxyl radicals damage to cellular and capillary membranes leading to loss of function and cell death (6).

FIGURE 19.3Xanthine Oxidase (XO) pathway activation by ischaemia-reperfusion and the production of reactive oxygen species. Ischaemia prevents oxidative phosphorylation (1) and cellular ATP cannot be regenerated. This leads to the accumulation of AMP and, in turn, hypoxanthine. Ischaemia also causes the accumulation of intracellular calcium (2). This catalyses the conversion of xanthine dehydrogenase (XD) to xanthine oxidase (XO) Upon reperfusion oxygen is supplied (3) and this provides the final substrate to allow XO to convert hypoxanthine to xanthine, producing superoxide as a by-product (4). During ischaemia iron is released from cytochrome, haemoglobin and other haem containing molecules (5). This iron catalyses the Fenton-Haber-Weiss reaction producing hydroxyl radicals from superoxide. These hydroxyl radicals damage to cellular and capillary membranes leading to loss of function and cell death (6).

From: 19, Compartment Syndromes

Cover of Mechanisms of Vascular Disease
Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists [Internet].
Fitridge R, Thompson M, editors.
Adelaide (AU): University of Adelaide Press; 2011.
© The Contributors 2011.

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