The following biochemical mechanism contribute to cell membrane damage:
A. Mitochondrial dysfunction- Defective mitochondrial function results in decreased phospholipid synthesis, which affects all cellular membrane. At the same time increase cytosolic Ca++ activate phospholipases and leading to breakdown of phospholipids. The net result is a depletion of phospholipids from the mitochondria and other dellular membranes and accumulation of free fatty acids. In the mitochondria this changes causes permeability defects.
B. Loss of membrane phospholipids: This is because activation of endogenous phospholipases by increased levels of cytosolic calcium, phospholipid loss can also occur secondary to decreased ATP-dependant reacylation or diminished de novo synthesis of phospholipids.
C. Cytoskeletal abnormalities: Activation of proteases by increased cytosolic Calcium may cause damage to elements of the cytoskeleton.
D. Reactive oxygen species: Partially reduced oxygen free radicals cause injury to cell membranes and to other cell constituents.
E. Lipid breakdown products: These includes unestirified free acids, acyl carnitine and lysophospholipids catabolic products that are known to accumulate in injured cells as a result of phospholipid degradation. They have detergent effect on membrane.
A. Mitochondrial dysfunction- Defective mitochondrial function results in decreased phospholipid synthesis, which affects all cellular membrane. At the same time increase cytosolic Ca++ activate phospholipases and leading to breakdown of phospholipids. The net result is a depletion of phospholipids from the mitochondria and other dellular membranes and accumulation of free fatty acids. In the mitochondria this changes causes permeability defects.
B. Loss of membrane phospholipids: This is because activation of endogenous phospholipases by increased levels of cytosolic calcium, phospholipid loss can also occur secondary to decreased ATP-dependant reacylation or diminished de novo synthesis of phospholipids.
C. Cytoskeletal abnormalities: Activation of proteases by increased cytosolic Calcium may cause damage to elements of the cytoskeleton.
D. Reactive oxygen species: Partially reduced oxygen free radicals cause injury to cell membranes and to other cell constituents.
E. Lipid breakdown products: These includes unestirified free acids, acyl carnitine and lysophospholipids catabolic products that are known to accumulate in injured cells as a result of phospholipid degradation. They have detergent effect on membrane.
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