Active bicarbonate

The bile add-independent fraction (200 ml) is to be found in the absence or near absence of bile acids. This fraction is formed chiefly in the perivenous acinus, (s. tab. 3.2) However, Na /K -ATPase, glutathione and an active bicarbonate transporter also play an important role. Likewise, the prostaglandins Ai, E and E2 stimulate the production of this fraction. 

Normally, with cations of alkali metals and nickel, specific anions are essential for the development of catalytic activity. Bicarbonate is the most efficient anion, followed by bismuthate, cyanate, and tungstate, all of lower, approximately equal, activity. In a few cases, the anions of copper and iron salts are of little significance in this connection. - Generally other anions investigated are inhibitory, even in the presence of iron salts. ... 

Nucleophilic attack by biotin on activated bicarbonate forms carboxybiotin. Because the nitrogen of an amide is not nucleophilic, it is likely that the active form of biotin has an enolate-like stmcture. Nucleophilic attack by the substrate (in this case, the enolate form of acetyl-CoA) on carboxybiotin transfers the carboxyl group from biotin to the substrate. 

All biotin-requiring enzymes follow the same three steps activation of bicarbonate by ATP, reaction of activated bicarbonate with biotin to form carboxybiotin, and transfer of the carboxyl group from carboxybiotin to the substrate. 

An alternative proposal, originally by Calvin and Pong (1959), exploits activation by the y-phosphate of ATP, to promote N(T) nucleophilicity, activate bicarbonate and provide an intramolecular carboxylation of the N(l ) position. Again, this mechanism may be subdivided into a stepwise pathway (Scheme 40d) and a concerted pathway (Scheme 40e), both involving the intermediacy of (9-phosphobiotin. There seems little advantage to the stepwise mechanism, since carboxyphosphate is generated, as in process (c), in a mechanism requiring an additional step. 

PEPC catalyses carboxylation of phosphoenol pyruvate (PEP), employing bicarbonate as carboxyl donor (Cooper and Wood, 1971). As in all such enzymes employing bicarbonate in place of CO2, the enzyme must activate bicarbonate towards carboxyl transfer. In this respect, as in others, PEPC resembles biotin-dependent carboxylases. Two distinct mechanisms are postulated for PEPC one involving the intermediacy of carboxyphosphate, the other a cyclic transition state and pseudorotation at phosphorus. 

A well-known example is the utilization of two molecules of ATP to drive the synthesis of carbamyl phosphate toward completion in the urea cycle (16) [44]. There is no chemical reason to use a second molecule of ATP to activate bicarbonate, because carbon dioxide itself is much more reactive toward nucleophilic attack... 

The function of ATP is to increase the reactivity of bicarbonate by converting it to activated bicarbonate —a compound with a good leaving group. To form activated bicarbonate, bicarbonate attacks the y-phosphorous of ATP and expels ADP (Section 16.23). Notice that activated bicarbonate is a mixed anhydride of carbonic acid and phosphoric acid (Section 16.20). 

This activated bicarbonate then reacts with biotin-bound enzyme to give I -iV-carboxybiotin, another activated form of carbonate. These two processes could occur in a concerted way and have been generally accepted for some time. The I -AT-carboxybiotin intermediate is stable under basic conditions but decarboxylates readily in acid medium. In the above example, carboxybiotin reacts with the enol form of acetyl-CoA to give malonyl-CoA and regenerated biotin. As expected, one oxygen from bicarbonate appears in the form of phosphate ion, the other two are in the carboxyl group of malonyl-CoA. 

Therefore, the ATP participation shifts the equilibrium toward the enol form. This last mechanism represents an example of activation by a substrate. The binding of bicarbonate, the substrate in question, increases the nucleo-philicity of the biotin cofactor. However, the formation of an activated bicarbonate, as proposed in the first mechanism, cannot be excluded. In all three cases examined the role of Mg(II) ions could be one of binding to ATP and promoting the formation of ADP. It is also remarkable that in all three cases the action of biotin is mediated by activation by phosphorylation, reminiscent of many reactions presented in Chapter 3. 

Carbonic anhydrase is an enzyme that catalyzes the hydration of carbon dioxide to bicarbonate The uncatalyzed hydration of carbon dioxide is too slow to be effective m transporting carbon dioxide from the tissues to the lungs and so animals have devel oped catalysts to speed this process The activity of carbonic anhydrase is remarkable It has been estimated that one molecule of this enzyme can catalyze the hydration of 3 6 X 10 molecules of carbon dioxide per minute... 

The word hormone is derived from the Greek hormaein, meaning to set in motion or to excite. It was used initially to define the activity of secretin [1393-25-5] (1), a gastrointestinal polypeptide released into the blood by the duodenal mucosa to stimulate pancreatic acinar cells to release bicarbonate and water. 

A.ctivated Carbonate Process. The activated carbonate process is based on absorption of CO2 by potassium carbonate (57) to give potassium bicarbonate. When the bicarbonate is heated it releases CO2, regenerating potassium carbonate. 

A large number of salts of sahcyhc acid have been prepared and evaluated for therapeutic or other commercial use. Table 7 hsts those most frequently referenced. Sodium sahcylate has analgesic, antiinflammatory, and antipyretic activities and was used extensively in the sixteenth and seventeenth centuries as a remedy, prepared from natural sources, for arthritis and rheumatism. In the 1990s the salt can be obtained directly from Kolbe-Schmitt carboxylation or by the reaction of sahcyhc acid with either aqueous sodium bicarbonate or sodium carbonate. The resulting mixture is heated until effervescence stops the salt is then isolated by filtration and evaporation to dryness at low temperatures. Generally, the solution must be kept slightly acidic so that a white product is obtained if the mixture is basic, a colored product results. The USP product contains 99.5—100.5% NaC H O (anhydrous). The May 1996 price was 8.15/kg (18). 

The efficiency of the weathering of rocks in using carbonic acid produced in the carbon cycle is affected by various hydrologic, environmental, and cultural controls. The fact that the principal anion in fresh surface water worldwide almost always is bicarbonate attests to the overriding importance of this process. Exceptions are systems in which evaporite minerals are available for dissolution by groundwater or where human activities are major sources of sulfate or chloride inflow. 

Medical Uses. Citric acid and citrate salts are used to buffer a wide range of pharmaceuticals at their optimum pH for stabiUty and effectiveness (65—74). Effervescent formulations use citric acid and bicarbonate to provide rapid dissolution of active ingredients and improve palatabiUty. Citrates are used to chelate trace metal ions, preventing degradation of ingredients. Citrates are used to prevent the coagulation of both human and animal blood in plasma and blood fractionation. Calcium and ferric ammonium citrates are used in mineral supplements. 

The quaternary fraction of pot curare, after the removal of some neoprotocuridine, was separated into a portion salted out by sodium bicarbonate, and a portion not so precipitated. The latter was fractionated on a plan described in the original, the most active product obtained being an amorphous iodide with a paralysing dose of 1- 5 mg. per kilo frog. This iodide was phenolic, gave the Millon reaction, but no strychnine-like reaction with bichromate and sulphuric acid. No crystalline product could be isolated, but on complete methylation certain of the fractions yielded crystalline methiodides as follows —... 

A mixture of the epoxide ca. 5 mmol), sodium azide (6 g, activated by the method of Smith) and 0.25 ml of concentrated sulfuric acid in 70 ml of dimethyl sulfoxide is heated in a flask fitted with a reflux condenser and a drierite tube on a steam bath for 30-40 hr. (Caution carry out reaction in a hood.) The dark reaction mixture is poured into 500 ml of ice water and the product may be filtered, if solid, and washed well with water or extracted with ether and washed with sodium bicarbonate and the water. The crude azido alcohols are usually recrystallized from methanol. 

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