The interrelationship of the concentration of hydrogen ions, bicarbonate ions, carbon dioxide and calcium ions in the regulation of renal gluconeogenesis in the rat

1. The interrelationship of acidosis and Ca(2+) on the stimulation of gluconeogenesis by rat kidney-cortex slices was studied. 2. Ca(2+) stimulated gluconeogenesis from glutamine, glutamate, 2-oxoglutarate, succinate, malate, pyruvate, lactate and fructose, but not from galactose. 3. The [Ca(2+)] needed for optimum gluconeogenesis was about 2mm, but at this concentration, acidosis, produced in vitro by a decrease of [HCO(3) (-)] in the medium at constant pCO(2) or by an increase in pCO(2) at constant [HCO(3) (-)], did not stimulate gluconeogenesis. 4. In the absence of Ca(2+), acidosis (low [HCO(3) (-)]) stimulated gluconeogenesis from glutamine, glutamate, 2-oxoglutarate, succinate, malate, pyruvate and lactate but not from fructose or galactose. With succinate as substrate, the stimulatory effect of acidosis (low [HCO(3) (-)]) disappeared at Ca(2+) concentrations above 1.0mm. 5. The [HCO(3) (-)] was the most important determinant of the acidosis effect since a decrease of pH caused by an increase in pCO(2) did not uniformly stimulate gluconeogenesis, whereas a decrease in [HCO(3) (-)] without a change in pH consistently stimulated glucose formation in a way similar to the stimulation produced by acidosis (low [HCO(3) (-)]) in the absence of Ca(2+). 6. Acidosis in vitro inhibited the rate of decrease of activity of phosphoenolpyruvate carboxylase in slices, and Ca(2+) caused an increase in the activity of fructose 1-phosphate aldolase. 7. Respiratory acidosis in vitro caused an increase in the activity of phosphoenolpyruvate carboxylase in kidney cortex and an increase in gluconeogenesis from glutamine. 8. Possible points of interaction between Ca(2+), H(+) and HCO(3) (-) with the gluconeogenic sequence are discussed.     

Proteins,channels and crowded ions

Ion channels are proteins with a hole down their middle that control a vast range of biological function in health and disease. Selectivity is an important biological function determined by the open channel, which does not change conformation on the biological time scale. The challenge is to predict the function—the current of ions of different types and concentrations through a variety of channels—from structure, given fundamental physical laws. Walls of ion channels, like active sites of enzymes, often contain several fixed charges. Those fixed charges demand counter ions nearby, and the density of those counter ions is very high, greater than 5 molar, because of the tiny volumes of the channel's pore. Physical chemists can now calculate the free energy per mole of salt solutions (e.g. the activity coefficient) from infinite dilution to saturation, even in ionic melts. Such calculations of a model of the L-type calcium channel show that the large energies needed to crowd charges into the channel can account for the substantial selectivity and complex properties found experimentally. The properties of such crowded charge are likely to be an important determinant of the properties of proteins in general because channels are nearly enzymes.     

Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH.

Evidence is given for a high density of negative surface charge near the sodium channel of myelinated nerve fibres. The voltage dependence of peak sodium permeability is measured in a voltage clamp. The object is to measure voltage shifts in sodium activation as the following external variables are varied: divalent cation concentration and type, monovalent concentration, and pH. With equimolar substitution of divalent ions the order of effectiveness for giving a positive shift is: Ba equals Sr less than Mg less than Ca less than Co approximately equal to Mn less than Ni less than Zn. A tenfold increase of concentration of any of these ions gives a shift of +20 to +25 mV. At low pH, the shift with a tenfold increase in Ca-2+ is much less than at normal pH, and conversely for high pH. Soulutions with no added divalent ions give a shift of minus 18 mV relative to 2 mM Ca-2+. Removal of 7/8 of the cations from the calcium-free solution gives a further shift of minue 35 mV. All shifts are explained quantitatively by assuming that changes in an external surface potential set up by fixed charges near the sodium channel produce the shifts. The model involves a diffuse double layer of counterions at the nerve surface and some binding of H+ions and divalent ions to the fixed charges. Three types of surface groups are postulated: (1) an acid pKa equals 2.88 charge density minus 0.9 nm- minus 2; (i) an acid pKa equals 4.58, charge density minus 0.58 nm- minus 2; (3) a base pKa equals 6.28, charge density +0.33 nm- minus 2. The two acid groups also bind Ca-2+ ions with a dissociation constant K equals 28 M. Reasonable agreement can also be obtained with a lower net surface charge density and stronger binding of divalent ions and H+ ions.     

RNA structure, metal ions, and catalysis

Several new and unexpected insights into the metalloenzymology of ribozymes have been achieved in the past year. From a mechanistic point of view, the NMR and crystal structures of a small Pb(2+)-dependent ribozyme have been particularly revealing.     

Effect of zinc ions, manganese and lead ions on the thermostable proteins of carp liver

Effect of comparatively low concentration of the zinc, manganese, lead ions (0.1, 0.13 and 0.01 mg/l respectively) on the thermostable proteins (TP) of the carp liver after fish incubation for 14 days was studied. It is revealed that about 30 of zinc, 40% of manganese and 6% of lead were bound in the TP solution. The results of chromatography on Sephadex G-75 show, that the metallothionein-like proteins (MT, M-6 kDa) were the primary metal-binding proteins among the TP for zinc and manganese, and the heavy fraction of TP (M-60 kDa)--for lead. Under the action of each of the metallions its content in the TP is significantly increased. The distribution of metals among TP compounds is similar to that in the control. The metals action causes specific changes of the heavy fraction properties (UV spectrum, SH-groups content). The properties of MT do not change significantly under the control value.     

Genomics,Proteomics & Bioinformatics

Unofficial Impact Factor 0.885 in 2011* Aims and Scope Genomics,Proteomics & Bioinformatics(GPB,ISSN 1672-0229) is a peer-reviewed international journal in English since 2003.GPB is sponsored by Beijing Institute of Genomics,Chinese Academy of Sciences and Genetics Society of     

Genomics,Proteomics & Bioinformatics

正Aims and Scope The goals of Genomics,ProteomicsBioinformatics(GPB)are to disseminate new frontiers of its focused research fields,to publish high-quality discoveries in a fast-pace,and to promote open access and prompt online publication for efficient publishing.GPB publishes high-quality papers from the frontier research in the fields of genomics,