Calcium complexes nucleotides

Most of this section will be devoted to summarizing information relating to the stability constants reported for complexes of this group of Ca2+-binding ligands. However, we shall precede this main part with a short mention of a few relevant structures. Other properties of calcium phosphates and phosphonates will be mentioned in Sections VIII.B.4 and VIII.D below. An overall view of complexes of nucleosides, nucleotides, and nucleic acids is available (670). 

Ral has attracted much interest in recent years, not least because it was demonstrated to mediate part of Ras function as described above. In contrast to Rap, which rather inhibits Ras signaling, Ral is part of one of the essential Ras-activated pathways. Moreover, it has proved to be acting in parallel with the Raf pathway in cell transformation induced by oncogenic Ras [37, 77]. The case of Ral demonstrates the complexity - and the incomplete knowledge and understanding - of signal transduction. Ral can also be activated by Rap mediated by Rif [103] and, alternatively, by binding of a calcium/calmodulin complex to the Ral C-terminus which obviously does not affect the nucleotide state of Ral [111]. 

A metal-nucleotide complex that exhibits low rates of ligand exchange as a result of substituting higher oxidation state metal ions with ionic radii nearly equal to the naturally bound metal ion. Such compounds can be prepared with chromium(III), cobalt(III), and rhodi-um(III) in place of magnesium or calcium ion. Because these exchange-inert complexes can be resolved into their various optically active isomers, they have proven to be powerful mechanistic probes, particularly for kinases, NTPases, and nucleotidyl transferases. In the case of Cr(III) coordination complexes with the two phosphates of ATP or ADP, the second phosphate becomes chiral, and the screw sense must be specified to describe the three-dimensional configuration of atoms. 

The second messenger molecules Ca2+ and cyclic AMP (cAMP) provide major routes for controlling cellular functions. In many instances, calcium (Ca2+) achieves its intracellular effects by binding to the receptor protein calmodulin. Calmodulin has the ability to associate with and modulate different proteins in a Ca2+-dependent and reversible manner. Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE, EC 3.1.4.17) is one of the key enzymes involved in the complex interactions that occur between the cyclic-nucleotide and Ca2+ second messenger systems (see Figure 13.2). CaMPDE exists in different isozymic forms, which exhibit distinct molecular and catalytic properties. The differential expression and regulation of individual phosphodiesterase (PDE) isoenzymes in different tissues relates to their function in the body. 

The duodenum and jejunum are capable of both absorption and secretion but absorption usually predominates. Regulation of intestinal secretion and absorption is highly complex and involves extrinsic and intrinsic neural stimuli, numerous receptor types and intercellular and intracellular transport pathways. Intracellular pathways of electrolyte transport involve membrane-associated receptors that activate cyclic nucleotide metabolism, membrane calcium channels and intracellular calcium metabolism, luminal and basal chloride channels and multiple sodium transport channels. Cholinergic stimuli tend to stimulate intestinal... 

Other causes of low serum calcium are less common. Hypoparathyroidism is due most commonly to parathyroid gland destruction during neck surgery (90%), and less commonly is idiopathic. Pseudohypoparathyroidism is biochemically similar to hypoparathyroidism however, these patients have inherited resistance to PTH and elevated concentrations of PTH. The molecular basis for the most common form, pseudohypoparathyroidism type I (Albright s hereditary osteodystrophy), is a reduction in guanine nucleotide regulatory complex. Ns, in the adenylate cyclase complex. 

The energy for Ca uptake can be derived either from substrate oxidation or from ATP hydrolysis. Since adenine nucleotides stabilise calcium phosphate precipitates the presence of adenine nucleotides stimulates Ca uptake, even if it is respiration-driven [125]. It is generally found that 2 Ca ions enter the mitochondrion at the expense of 1 ATP or its equivalent [124]. It is, however, less clear how many electrical charges cross the membrane during this process. Most experiments indicate that free Ca, carrying 2 positive charges, is the mobile species [126,127]. Some experiments suggest, however, that a complex of the form (CaX), in which X is a monovalent anion (for instance phosphate), moves [128]. The distinction between these two possibilities plays an important role in the discussion on the stoichiometry of the mitochondrial H pump. 

---