life and death in cells, glycolysis and apoptosis

All organisms reqire energy for their activity.
Central to this is glycolysis . Glycolysis is the pathway in which glucose is metabolised before splitting into two interconvertible 3-carbon molecules . These reactions take place in the cell cytoplasm. The first three steps involve reactions which lead to a doubly phosphorylated fructose derivative, Glucose 1-phosphate, glucose 6-phosphate and fructose 6-phosphate readily interconvert and thereby form a single metabolic pool. Glucose 1-phosphate is the first product in the catabolism of storage polysaccharides, e.g. starch, Glucose 6-phosphate is the first hexose phosphate generated when free glucose is metabolised and fructose 6-phosphate is the first hexose phosphate formed when the carbohydrate is derived from non carbohydrate precursors.
Glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) readily interchange through the action of the enzyme glucose phosphate isomerase. The available amount is dependent upon the phosphorolysis of storage polysaccharides, yielding glucose 1-phosphate, by the phosphorylation of glucose yielding G6P or by gluconeogenesis of F6P. The subsequent catabolic steps are:
glycolysis with F6P as the starting point
the pentose phosphate pathway which uses G6P.
Alternatively G6P and F6P can be converted into storage polysaccharides with G6P acting as the starting point. G6P can also be hydrolysed to yield free glucose to be transported in the blood to peripheral tissues.
Cell death apoptosis , Apoptosis is a coordinated, programmed, genetically regulated form of cell death. A multicellular organism must sustain equal rates of cell generation and cell death to maintain a constant size. Senescent, damaged or abnormal cells that could interfere with organ function must be removed. Physiological cell death is not a random process. Apoptosis is important in organ atrophy and during disease with a decrease in cell numbers. Apoptosis is a rapid process and is directed towards scattered individual cells rather than all the cells in a particular area. It occurs during embryogenesis in the process of tissue turnover and after withdrawal of a trophic hormone from its target tissue. Apoptosis is a mechanism whereby organs and digits in the hand and foot are sculptured out in the evolving foetus.
In the adult some 10 billion cells die each day to balance new production. An example of apoptosis in the adult is a shedding of intestinal cells. Apoptosis may be important in autoimmune disease, degenerative diseases and ageing. The decline in body cell mass with age is probably controlled genetically, as it is related to life span.
Early in apoptosis the distinct morphological features include compaction of chromatin against the nuclear membrane, cell shrinkage and preservation of organelles, detachment from surrounding cells and nuclear and cytoplasmic budding to form membrane-bound fragments (apoptotic bodies). These are rapidly removed by adjacent parenchymal cells or macrophages. An enzyme system caspases dismantle the cell from within in an orderly manner. These are triggered by the release of cytochrome c. Proteins of the BCL-2 family are key regulators of apoptosis , either stimulating or preventing apoptosis. . A pro-apoptotic BCL-2 protein is BAD, which when phosphorylated is sequestrated into inactive complexes and no longer cause cell death.
Mitochondria have a central role in both glycolysis and apoptosis BAD may be an important protein in life and death of cells. BAD is also present in large protein complexes which regulate BAD phosphorylation eg protein kinase A, protein phosphatase 1 and surprisingly glucokinase. Central to glycolysis.
There are other close links between apoptosis and glycolysis by control mechanisms e.g. growth factors. BAD may have an influence on metabolism. Glucose mediated phosphorylation of BAD might increase glycolysis and prevent cell death.
Downward (2003) Nature , 424, 896-7

Martin Eastwood
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