Importance Of Carbonic Anhydrase Research Articles

CARBONIC ANHYDRASE IN <i>Plasmodium falciparum</i>: A USEFUL TARGET FOR ANTIMALARIAL DRUG DESIGNING AND MALARIA blocking TRANSMISSION COMPOUNDS

Carbonic anhydrase is a metalloenzyme that catalyzes the reversible conversion of CO2 to bicarbonate, anessential metabolic component used by the malaria parasites for de novo synthesis of pyrimidines and theexflagelation of gametocytes inside the mosquito vector. Carbonic anhydrase is involved in the transportof bicarbonate. This enzyme participates in transport of bicarbonate inside and outside the cells to avoidan imbalance in the system CO2/HCO3- and alteration of pH in the interior of the cell as well as in theintercellular space. Therefore, inhibition of this enzyme either in the parasite or the insect vector, couldlead to a decrease in replication and to the detriment and/or death of the parasite. Given the importance ofcarbonic anhydrase in the metabolism, development and survival of Plasmodium, it could be postulatedthat carbonic anhydrase inhibitors are both a therapeutic and a blocking transmission alternative. Previousstudies have demonstrated the in vitro anti-Plasmodium activity of some inhibitors. However, it isnecessary to determine their effectiveness to confirm its usefulness in the treatment or blocking malariatransmission and the mechanism by which these inhibitors are able to affect the development of theparasite in the mosquito vector. In this paper we present a review about the role of carbonic anhydrase inPlasmodium spp and using some specific inhibitors as a strategy for malaria treatment and transmissionblocking strategy. Articles published in the past 59 years identified from bibliographic database (PubMedand ScienceDirect) and papers collected by the authors were included.

Is there a requirement for an external carbonic anhydrase in the extremely acid-resistant green algaDunaliella acidophila?

The importance of carbonic anhydrase (CA) for the extremely acid-resistant green alga Dunaliella acidophila, acclimated to low or high CO2, was investigated by (1) measuring the total activity of CA in this alga as well as its intracellular distribution, (2) analysing protein by polyacrylamide gel electrophoresis and immunobiological techniques, and (3) studying the effect of impermeant and permeant inhibitors of CA on photosynthesis as well as the dependence of the substrate kinetics of photosynthesis on the CO2 supply during culture. Dunaliella parva, a salt-tolerant but neutrophilic member of the same genus, was used as reference system. Results demonstrate that D. acidophila cells contain only 5–15% of the total CA activity measured in D. parva. A similar ratio applies also to the “external” (= periplasmatic or plasma-membrane-bound) CA activity of D. acidophila. The majority of the CA activity in both algae was found to be localized in membranes. In both algae acclimation to low CO2 concentration cau...

The importance of carbonic anhydrase B and C for the unloading of CO2 by the human erythrocyte.

Carbonic anhydrase (carbonate dehydratase, EC 4.2.1.1) isoenzymes HCA B and HCA C from human erythrocytes were purified by affinity chromatography and characterized kinetically at 37 degrees C in 25 mM N-methylimidazole buffer, I = 0.15, pH 7.1, using a pH-indicator stopped-flow technique. The rate constants for the uncatalyzed hydration of CO2 and dehydration of H2CO3 were 0.12 . s-1 and 58 . s-1, respectively, Km and turnover numbers in the hydration reaction were 14.0 mM and 19.1 . 10(5) . s-1 for HCAC and 3.3 mM and 0.56 . 10(5) . s-1 for HCA B. Km and turnover numbers in the dehydration reaction were 70 mM and 5 . 10(5) . s-1 for HCA C and 16.8 mM and 0.27 . 10(5) . s-1 for HCA B. Ki for chloride was 14 mM for HCA B and greater than 200 mM for HCA C. Ki for acetazolamide was 0.9 microM against HCA B and 16 nM against HCA C. The rates of hydration of CO2 in hemolysates with known concentrations of HCA B and HCA C, and in mixtures of purified HCA B and HCA C with concentrations near those in the erythrocyte, were similar to the rates calculated from the kinetic parameters of each isoenzyme. HCA B is 86% inhibited by chloride in vivo. This strong inhibition, together with the low specific activity, explains why HCA B only accounts for 10% of the total carbonic anhydrase activity of the erythrocyte, en spite the cellular concentration HCA B is 8 times higher than that of HCA C. HCA B and HCA C can together accelerate the intracellular CO2-reaction 23 000-fold, which gives a margin of 25-fold over physiological needs in hard work and 50-fold at rest. Perceptible physiological effects on respiration should therefore be seen when total carbonic anhydrase activity of erythrocytes is 96 to 98% inhibited. These degrees of inhibition are achieved when plasma concentrations of acetazolamide reach 2 and 5 microM, respectively.