Calcification intracellular

Simkiss, K. Intracellular pH during calcification. A study of the avian shell gland. Biochem. J. Ill, 254 (1969)... 

Several lines of evidence indicate that carbonic anhydrase is related to calcification in two possible ways (1) as a simple catalyst of C02 hydration, and (2) as a protector of fixed calcium at the nucleation site. The idea has even been advanced that in calcareous algae photosynthesis is the driving force in carbonate deposition by consuming C02 molecules from an intracellular pool of bicarbonate. 

Once inside the cell, HCO3 is converted to CO2 by the enzyme, carbonic anhydrase. CO2 is then fixed by carboxydismutase and OH is excreted to maintain ionic balance. Carbonic anhydrase is also associated with the extracellular carbonate dissolution by boring organisms (Schneider, 1976) and with the C02-transfer system for intracellular calcification. It represents a key enzyme in the biological cycling of carbonate (Degens, 1976 Raven, 1974). 

According to Arnott and Pautard (1970) and Degens (1976) the organization of calcification, either intracellularly or on excreted organic matrices, may be specified by the genetic code. Degens (1976) assumed that a carrier protein serves as a template for an acidic polypeptide (the mineralization... 

Intracellular calcification within vesicles, or in vacuoles within syncytia, is present in a wide variety of tissues in every phylum examined thus far. Commonly, the calcium deposited takes the form of amorphous calcium spherules formed in vesicles associated with the endoplasmic reticulum or Golgi sys-... 

The CO2/HCO3 system involved in calcification can be considered in a somewhat similar manner. The question as to whether the carbonate ion of the mineral is derived from extracellular fluids originating in the external medium or whether it arises from intracellular metabolic CO2 has been examined in corals (Pearse, 1970), molluscs (Campbell and Speeg, 1969 Wheeler et ah, 1975), and arthropods (Greenaway, 1974c) (see pp. 74, 80, 87). It may be that both sources contribute to the skeletal carbonate. The significance of determining the intracellular and extracellular sources of carbonate is not simply that it enables one to draw up a balance sheet of input or output but that it serves as an indication of the participation of cellular function in mineralization processes. 

The morphological classification adopted in an earlier section (see pp. 89— 91) emphasizes the important role of membrane systems in calcification. Membranes, both in intracellular and extracellular calcification, are thought to be involved in an active transport of calcium to the site of calcification. They may also be involved in facilitating the availability of bicarbonate ions and in removing protons released during calcification. Thus, all the main ion species involved in biological calcification may be controlled by membrane processes. The ions are related according to the empirical equation... 

The deposition of mineral on one side of a cell membrane is affected by both the availability of calcium and carbonate ions and also by their interaction with other ions. Interfering ions not only impede the effective collisions of calcium and carbonate but they may also form ion pairs with the calcium and carbonate ions (Skirrow, 1975). Mg " and PO " may also interfere with the growth of the crystJil lattice so that, in their presence, the rate of calcification may be reduced and a particular crystal type may be favoured (Kitano et al., 1976). One of the functions of cellular membranes is probably to control the ionic composition of invertebrate skeletons and that of some intracellular mineral deposits. 

Van Rooijen N (1993) Extracellular and intracellular action of clodronate in osteolytic bone diseases a hypothesis. Calcif Tissue Int 52 407... 

It was also found that despite normal calcium levels being present in the blood during hypomagnesaemia, aberrations in Ca metabolism were observed. These were manifest as calcification of the kidneys (Greenberg et al., 1938), liver (Hajj and Sell, 1969), aorta (Britton and Stokstad, 1970), and heart muscle (Forbes, 1965). Disturbances in phosphorus metabolism characterized by hypophophatemia have also been reported, as well as intracellular abnormalities. In rats, the mitochondria became swollen and oxidative phosphorylation by liver tissue decreased (Chutkow, 1964). 

In dystrophic calcifications, the mineralisation occurs without a systemic mineral imbalance as a response to previous cell injury on the microscopic level or any soft tissue damage, including that involved in implantation of medical devices or bioprosthetic heart valves [25], Injury and cell death can cause the release of intracellular phosphate ions and fatty acids into the extracellular environment, where sparingly soluble calcium salts are precipitated in tissues. This type of calcification is particularly common in atherosclerosis and diseases associated with chronic inflammation. 

Pathological intracellular calcifications can also occur in conditions associated with hypercalcaemia [26] - excess levels of calcium in the blood, caused, e.g. by hyperparathyroidism (excess secretion of parathyroid hormone by overactive parathyroid glands which normally regulate calcium levels tightly) or malignancy [27]. Intramitochondrial cdcifications often precede necrosis, and fusion or rupture of calcified mitochondria results in calcareous masses in the cytoplasm or outside of the cell. Much progress has been made in the ultramicroscopic identification and systematic classification of these calcifications [28]. 

The body sodium is distributed into intracellular and extracellular pools. The sodium contained in these pools exchanges readily with the exogenous sodium. Isotope studies demonstrate that the intracellular sodium is rapidly exchanged with the extracellular sodium. In addition to the two large sodium pools, a smaller sodium pool is located in the skeleton. The sodium in bone is only slowly exchanged with exogenous sodium. The presence of sodium in the bone has been discussed in the chapter on calcification. 

---