Homoeostasis

In summary, the lysophospholipids are local mediators that regulate development, tissue regeneration and homoeostasis, but also play a role in inflammation, arteriosclerosis and cancer. 

J. Benters, U. Flogel, T. Schafer, D. Leibfritz, S. Hechtenberg, D. Beyersmann, Study of the interactions of cadmium and zinc ions with cellular calcium homoeostasis using F-19-NMR spectroscopy, Biochem. J. 322 (1997) 793-799. 

Van der Lelie, D. Schwuchow, T. Schwidetzky, U. Wuertz, S. Baeyens, W. Mergeay, M. Nies, D.H. Two-component regulatory system involved in transcriptional control of heavy-metal homoeostasis in Alcaligenes eutrophus. Mol. Microbiol., 23, 493-503 (1997)... 

Rutter, G. A., Da Silva Xavier, G. and Leclerc, I., 2003, Roles of 5 -AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis, Biochem J, 375, pp 1-16. 

Laplante, J. M., O Rourke, F., Lu, X., Fein, A., Olsen, A. and Feinstein, M. B., 2000, Cloning of human Ca2+ homoeostasis endoplasmic reticulum protein (CHERP) regulated expression of antisense cDNA depletes CHERP, inhibits intracellular Ca2+ mobilization and decreases cell proliferation. Biochem J 348 Pt 1, 189-99. 

The liver is the principal organ for glucose homoeostasis and maintenance of blood glucose and has an important role in the maintenance of plasma carbohydrate levels. Glucose, which is absorbed from the GIT, is transported to the liver where it is stored as glycogen. Approximately 80 g of glycogen is stored in the liver, and approximately 160 g of glucose per day is needed for normal body functions. 

The results of investigations available so far have demonstrated that the liver assumes a central role in preserving the homoeostasis of trace elements. Liver diseases may also lead to persistent disturbances in the metabolism of trace elements which are of clinical significance and may require therapeutic steps. (57, 66)... 

A high amount of bicarbonate is constantly being produced in the body. Degradation of 100 g protein yields approximately 1 mol bicarbonate (= 61 g). Bicarbonate neutralization takes place via the urea cycle too, as the synthesis of 1 mol urea requires 2 mol bicarbonate. Besides the lungs and kidneys, the liver therefore also plays an important role in acid-base metabolism and is partly responsible for pH homoeostasis. 

Thus the bicarbonate buffer in the liver with its components CO2 and HC03 is also used for maintaining pH homoeostasis. The various cellular and subcellular compartments can only keep their own specific pH values constant provided the pH value of the extracellular space is not subject to major fluctuations. A constant balance between the formation and excretion of CO2 and HCOj must therefore be guaranteed. Bicarbonate neutralization takes place, energy-driven and irreversibly, in the urea cycle. In this context, HC03 is considered to be a relatively strong base, whereas NH4+ is regarded as a weak acid. 

Maintaining a physiological equilibrium (= concentration) of cell-formed reactive oxygen intermediates by means of highly sensitive regulation mechanisms is a fundamental process of biomolecular homoeostasis. 

Autoimmunity is essential in each individual - and normally it does exist. Natural autoreactive antibodies ensure immunological homoeostasis. The immune system is well-equipped to fulfil its tasks of distinguishing between endogenous and exogenous structures. 

Oedema and ascites call for extensive therapeutic measures. The daily life of the liver patient is additionally impaired by this condition, which may even be life-threatening. Awareness of the pathogenic factors makes it possible to apply prophylactic measures to prevent a disruption of water-electrolyte homoeostasis and to ensure appropriate therapy. 

The progressive course of cell damage through to cell death is mainly characterized by two biochemical metabolic processes (1.) oxidative stress and (2.) disruption of intracellular Ca homoeostasis. These two processes interact, so that the oxidative stress induces the disruption of calcium homoeostasis there are also, however, other reciprocal actions/effects involving further cellular metabolic processes. (27)... 

Disrupted calcium homoeostasis Normal concentrations of ionized calcium in the cytosol (0.05-0.2 pM), in the overall liver cell (0.5-2.0 pM) and in the extracellular space (1.0 pM) maintain the function of numerous Ca-dependent enzymes and structural elements of the liver cell. Calcium homoeostasis is maintained by the regulatory functioning of all Ca transportation systems, energy supply in the form of ATP and intactness of the biomembranes. Defective calcium homoeostasis can cause an increase in calcium in the cytosol, which in turn activates calcium-dependent enzymes, alters the metabolic functions of the cell and disrupts the gap junctions and tight junctions. These biochemical changes result in various forms of hepatocellular degeneration and ultimately in cell death, (s. fig. 21.12)... 

Fig. 21.12 Biochemical causative mechanisms of hepatocellular degeneration and cell death due to oxidative stress and disruptions of cellular calcium homoeostasis (similar to a vicious circle)...

Xenobiotics Xenobiotics are defined as exogenously administered or endogenously produced foreign substances that impair and ultimately damage the ecology and homoeostasis of cellular systems. This definition also includes medicinal preparations, (s. p. 52)... 

Zinc Treatment with zinc is considered to be an alternative therapy for mobilizing copper deposits (T.U. Hoogen-RAAD et al., 1978). (343) Zinc causes inhibition of intestinal copper resorption and stimulates the synthesis of metal-lothionein in the liver and intestinal mucosa. The recommended dosage is 3 (-4) x 50 mg/day, one hour before meals. The duration of administration and the dose are adjusted in line with therapeutic success. Zinc can also be used in long-term treatment (i.e. maintenance of copper homoeostasis) following the initial release of copper deposits by means of penicillamine. Side effects have been reported in the form of gastrointestinal complaints. There is an increase in AP as well as amylase and lipase. (367, 387)... 

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