scholarly journals Carbonic acid production and the role of carbonic anhydrase in decarboxylation in brain

1969 ◽  
Vol 114 (4) ◽  
pp. 703-705 ◽  
Author(s):  
John W. Severinghaus ◽  
F. Norman Hamilton ◽  
Shamay Cotev

Sudden oxygenation of a thin film of rat brain homogenate, suspended between the surface of a glass pH-sensitive electrode and a gas-permeable membrane, is accompanied by a fall in pH, which is greater when carbonic anhydrase is inhibited. The result suggests that oxidative decarboxylation yields carbonic acid (HCO3− and H+), which dissociates to form molecular carbon dioxide. Brain carbonic anhydrase facilitates the formation of carbon dioxide from the decarboxylation products.

2011 ◽  
Vol 14 (4) ◽  
pp. E9 ◽  
Author(s):  
Paul K. Addo ◽  
Robert L. Arechederra ◽  
Abdul Waheed ◽  
James D. Shoemaker ◽  
William S. Sly ◽  
...  

2003 ◽  
Vol 99 (4) ◽  
pp. 924-928 ◽  
Author(s):  
Harvey J. Woehlck ◽  
Mary Otterson ◽  
Hyun Yun ◽  
Lois A. Connolly ◽  
Daniel Eastwood ◽  
...  

Background Carbon dioxide is the preferred insufflating gas for laparoscopy because of greater safety in the event of intravenous embolism, but it causes abdominal and referred pain. Acidification of the peritoneum by carbonic acid may be the major cause of pain from carbon dioxide insufflation. Carbonic anhydrase is an enzyme that increases the rate of carbonic acid formation from carbon dioxide. Because acetazolamide inhibits carbonic anhydrase, the authors hypothesized that the pain caused by carbon dioxide insufflation may be decreased by the administration of acetazolamide. Methods A prospective, randomized, double-blind study of 38 patients undergoing laparoscopic surgery during general anesthesia was performed. Acetazolamide (5 mg/kg) or a saline placebo was administered intravenously during surgery. Pain was rated on a visual analog scale (0-10) at four times: when first awake, at discharge from the recovery room, when discharged from the hospital, and on the day after surgery. The site and quality of pain were recorded, as were medications and side effects. Results Initial referred pain scores were lower after acetazolamide (1.00 +/- 1.98; n = 18) than after placebo (3.40 +/- 3.48; n = 20; P = 0.014), and 78% of patients in the acetazolamide group had no referred pain; however, only 45% patients in the placebo group had no referred pain. Incisional pain scores were not statistically different, and referred pain scores were similar at later times. Conclusions Acetazolamide reduces referred but not incisional pain after laparoscopic surgical procedures. The duration of pain reduction is limited to the immediate postsurgical period.


2018 ◽  
Vol 128 (5) ◽  
pp. 873-879 ◽  
Author(s):  
Erik R. Swenson

Abstract Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long-abiding interest in acid–base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism. Dr. John Severinghaus has posited that hydrogen ion and bicarbonate are the direct end products in the Krebs cycle. In the late 1960s, he showed in brain and brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor, reduces intracellular pH. This led him to conclude that hydrogen ion and bicarbonate are the end products, and the role of intracellular carbonic anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis. Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs cycle, a more widely accepted view, and that acetazolamide prevents rapid intracellular bicarbonate formation, which can then codiffuse with carbon dioxide to the cell surface and there be reconverted for exit from the cell. Loss of this “facilitated diffusion of carbon dioxide” leads to intracellular acidosis as the still appreciable uncatalyzed rate of carbon dioxide hydration generates more protons. This review summarizes the available evidence and determines that resolution of this question will require more sophisticated measurements of intracellular pH with faster temporal resolution.


1979 ◽  
Vol 88 (2) ◽  
pp. 222-227 ◽  
Author(s):  
Jiri Prazma ◽  
Newton D. Fischer ◽  
W. Paul Biggers ◽  
David Ascher

The effect of carbon dioxide on oxygen tension in the endolymph was determined by the micropolarographic technique. Different concentrations (5% and 10% CO2) and different exposure times (3, 5, and 20 minutes) were investigated. The highest levels of Po2 in the endolymph (101.7, 93.9 and 69.5 mm Hg) were accomplished by respiration of 10% CO2, 90% O2, for 20, 5, and 3 minutes consecutively. The lowest Po2 increase, 50.7 mm Hg was observed after breathing 5% CO2, 90% O2 for 20 minutes. Extreme hypercapnia caused an increase of endocochlear potentials (EP) in all groups. In the second group EP increased from +79.3 to +84.9 and in all groups they had returned to the pretreatment level after CO2 discontinuation. These results support the theory that carbonic anhydrase participates in the generation of EP. At the same time that EP increased, cochlear microphonics declined and opposite after the breathing mixture was discontinued. The results permit the conclusion that high levels of Po2 in endolymph is achievable even with short periods of respiration with high CO2 mixture, and suggest the role of carbonic anhydrase during EP generation.


1998 ◽  
Vol 274 (1) ◽  
pp. F139-F147 ◽  
Author(s):  
Shuichi Tsuruoka ◽  
George J. Schwartz

Membrane-bound luminal carbonic anhydrase (CA) IV, by catalyzing the dehydration of carbonic acid into CO2 plus water, facilitates H+ secretion in the renal outer medullary collecting duct from the inner stripe (OMCDi). To examine the role of CA IV on H+ secretion, we measured net [Formula: see text] transport in perfused OMCDi segments and examined the effect on transport of two extracellular CA inhibitors, benzolamide and F-3500, aminobenzolamide coupled to a nontoxic polymer, polyoxyethylene bis(acetic acid) [synthesized and kindly provided by C. Conroy and T. Maren (C. W. Conroy, G. C. Wynns, and T. H. Maren. Bioorg. Chem. 24: 262–272, 1996)]. These agents would inhibit only the luminal CA enzyme. Dose titration curves for net[Formula: see text] flux were performed for each drug. Basal [Formula: see text] absorptive flux was 12 pmol ⋅ min−1 ⋅ mm−1in control segments and significantly increased to 16 pmol ⋅ min−1 ⋅ mm−1in segments from 3-day acid-treated animals. The concentrations of benzolamide and F-3500 that inhibited[Formula: see text] absorption by 50% were ∼0.1 and ∼5 μM, similar to the K i for CA IV inhibition by these agents (0.2 and 4.0 μM, respectively; T. Maren, C. W. Conroy, G. C. Wynns, and D. R. Godman. J. Pharmacol. Exp. Ther. 280: 98–104, 1997). Adding exogenous CA to the inhibitor in the perfusate nearly restored basal [Formula: see text] transport, suggesting that cytosolic CA II was not inhibited by these impermeant inhibitors. In OMCDi segments from acidotic rabbits, the concentrations of benzolamide and F-3500 that inhibited[Formula: see text] absorption by 50% were 50 and 500 μM, respectively, >100 times the K i for CA IV inhibition and for inhibition of [Formula: see text]transport in control tubules. Thus, in the OMCDi, doses of extracellular CA inhibitors that inhibited ∼50% of CA IV activity also comparably inhibited [Formula: see text] transport, indicating that H+ secretion depends in part on the availability of luminal CA IV activity. Acidosis substantially decreased the sensitivity of [Formula: see text]transport to CA inhibition.


The existence of carbonic anhydrase (carbonate dehydratase, EC 4. 2.1.1) in blood was suspected and sought because the rates of spontaneous hydration and dehydration of CO 2 and carbonic acid were slow compared with the rates of exchange of CO 2 with blood. The existence of the enzyme in absorbing and secreting epithelial tissues has, in contrast, often been sought because its presence was required for the operations of theoretical models for the movements of H + ions or HCO - 3 into or out of epithelial cells. In addition to the HCl-secreting gastric mucosal epithelium, the enzyme was subsequently found in the rumen, in the kidney, especially those of species that produce acid urine, in salivary gland, the liver and biliary duct system, the mucosa of the small intestine, caecum and colon, the choroid plexuses and ciliary body of mammals, in toad urinary bladder and in the Cl - secreting cells of fish gill. The presence of carbonic anhydrase in exocrine pancreas does not seem to be well established. The enzyme, of molecular mass about 30 kDa and containing one zinc atom, exists in three related forms: one of high specific activity and two of low specific activity, one of which is found in red skeletal muscle. Although most, but not all, types of erythrocyte contain both varieties, epithelia usually contain only the highactivity enzyme; however, ox rumen contains large quantities of the low-activity variety as do guinea-pig caecal and colonic mucosae. Salt transport in the intestinal tract is associated with movements of HCO - 3 and of H + ions, yet although carbon dioxide stimulates solute and fluid transport in the gall bladder and jejunum, and inhibitors of carbonic anhydrase reduce fluid and ion transport across many epithelia, the role of the enzyme in epithelial transport is not clearly understood. Knowledge of the rates of hydration and dehydration of CO 2 /HCO - 3 in the fraction of the tissue water responsible for the H + -HCO - 3 movements in many secretory epithelia is currently lacking.


1956 ◽  
Vol 185 (2) ◽  
pp. 426-429 ◽  
Author(s):  
Bruno K. Ochwadt ◽  
Robert F. Pitts

Five dogs were rendered hydropenic by withholding water for 20 hours and mildly alkalotic by the infusion of sodium bicarbonate intravenously in small amounts. Under these conditions alkaline urine was formed at approximately 1.0 cc/min. In 15 control periods the pCO2 of the urine exceeded that of the plasma, the ratio averaged 2.08 ± 0.44 (S.D.) with a range of 1.45–2.79. Following the intravenous administration of 100 mg of carbonic anhydrase as a priming dose and the infusion of the enzyme at a rate of 1 mg/min., the ratio in 25 experimental periods decreased to an average of 0.988 ± 0.14 (S.D.) with a range of 0.78–1.30. We conclude that the high carbon dioxide tensions commonly observed in alkaline urines result from delayed dehydration of carbonic acid to carbon dioxide in the renal tubule.


Author(s):  
Jin Young Kim ◽  
R. E. Hummel ◽  
R. T. DeHoff

Gold thin film metallizations in microelectronic circuits have a distinct advantage over those consisting of aluminum because they are less susceptible to electromigration. When electromigration is no longer the principal failure mechanism, other failure mechanisms caused by d.c. stressing might become important. In gold thin-film metallizations, grain boundary grooving is the principal failure mechanism.Previous studies have shown that grain boundary grooving in gold films can be prevented by an indium underlay between the substrate and gold. The beneficial effect of the In/Au composite film is mainly due to roughening of the surface of the gold films, redistribution of indium on the gold films and formation of In2O3 on the free surface and along the grain boundaries of the gold films during air annealing.


Sign in / Sign up

Export Citation Format

Share Document