scholarly journals Carbonic Anhydrases: Role in pH Control and Cancer

Metabolites ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 19 ◽  
Author(s):  
Mam Mboge ◽  
Brian Mahon ◽  
Robert McKenna ◽  
Susan Frost
Keyword(s):  
Ph Control ◽  
Carbonic Anhydrases

scholarly journals Characterization of a novel type of carbonic anhydrase that acts without metal cofactors

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yoshihisa Hirakawa ◽  
Miki Senda ◽  
Kodai Fukuda ◽  
Hong Yang Yu ◽  
Masaki Ishida ◽  
...  
Keyword(s):  
Active Site ◽  
Ph Control ◽  
Sequence Motif ◽  
Carbonic Anhydrases ◽  
Uncharacterized Protein ◽  
Metal Free ◽  
X Ray Crystallography ◽  
Control Respiration ◽  
Metal Cofactor ◽  
Protein Group

Abstract Background Carbonic anhydrases (CAs) are universal metalloenzymes that catalyze the reversible conversion of carbon dioxide (CO2) and bicarbonate (HCO3-). They are involved in various biological processes, including pH control, respiration, and photosynthesis. To date, eight evolutionarily unrelated classes of CA families (α, β, γ, δ, ζ, η, θ, and ι) have been identified. All are characterized by an active site accommodating the binding of a metal cofactor, which is assumed to play a central role in catalysis. This feature is thought to be the result of convergent evolution. Results Here, we report that a previously uncharacterized protein group, named “COG4337,” constitutes metal-independent CAs from the newly discovered ι-class. Genes coding for COG4337 proteins are found in various bacteria and photosynthetic eukaryotic algae. Biochemical assays demonstrated that recombinant COG4337 proteins from a cyanobacterium (Anabaena sp. PCC7120) and a chlorarachniophyte alga (Bigelowiella natans) accelerated CO2 hydration. Unexpectedly, these proteins exhibited their activity under metal-free conditions. Based on X-ray crystallography and point mutation analysis, we identified a metal-free active site within the cone-shaped α+β barrel structure. Furthermore, subcellular localization experiments revealed that COG4337 proteins are targeted into plastids and mitochondria of B. natans, implicating their involvement in CO2 metabolism in these organelles. Conclusions COG4337 proteins shared a short sequence motif and overall structure with ι-class CAs, whereas they were characterized by metal independence, unlike any known CAs. Therefore, COG4337 proteins could be treated as a variant type of ι-class CAs. Our findings suggested that this novel type of ι-CAs can function even in metal-poor environments (e.g., the open ocean) without competition with other metalloproteins for trace metals. Considering the widespread prevalence of ι-CAs across microalgae, this class of CAs may play a role in the global carbon cycle.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Example of Waste Water pH Control by Fuzzy

2007 ◽  
Vol 61 (3) ◽  
pp. 305-309
Author(s):  
Takayuki Ohkura
Keyword(s):  
Waste Water ◽  
Ph Control ◽  
Water Ph

Using microbial fatty acids to quantify, characterize and compare biofilm and suspended microbial populations in wastewater treatment systems

1998 ◽  
Vol 38 (4-5) ◽  
pp. 273-280 ◽  
Author(s):  
A. G. Werker ◽  
E. R. Hall
Keyword(s):  
Fatty Acid ◽  
Methyl Esters ◽  
Ph Control ◽  
Microbial Populations ◽  
Total Organic Carbon Removal ◽  
Operating Limits ◽  
Suspended Biomass ◽  
Kraft Mill Effluent ◽  
Microbial Fatty Acid ◽  
Influence Of Ph

Spectra of microbial fatty acid methyl esters were used to assess the influence of pH on the biofilm and suspended biomass populations within bench scale moving bed bioreactors treating bleached kraft mill effluent. The fatty acid spectral data were reduced by logcontrast canonical component analysis. The first canonical component differentiated biofilm from suspended populations and the second two appeared to indicate an influence of pH on microbial ecology. Thus, the biofilm and suspended microbial communities were distinct, as were the populations acclimated at pH 6 and pH 8. Experimental data for total organic carbon removal suggested that the more recalcitrant fraction of the influent was consumed by the slower growing, high SRT biofilm fraction of the biomass. Since the biofilm ecology was sensitive to pH within typical pH operating limits of full-scale systems, tighter pH control might improve treatment reliability in the event of process transients.

The anaerobic treatment of a ligno-cellulosic substrate offering little natural pH buffering capacity

1998 ◽  
Vol 38 (4-5) ◽  
pp. 29-35 ◽  
Author(s):  
C. J. Banks ◽  
P. N. Humphreys
Keyword(s):  
Ph Control ◽  
Anaerobic Treatment ◽  
Buffering Capacity ◽  
Single Stage ◽  
Stable Operation ◽  
Reactor Performance ◽  
Two Stage ◽  
Ph Buffering ◽  
Stage System ◽  
The Stability

The stability and operational performance of single stage digestion with and without liquor recycle and two stage digestion were assessed using a mixture of paper and wood as the digestion substrate. Attempts to maintain stable digestion in both single stage reactors were unsuccessful due to the inherently low natural buffering capacity exhibited; this resulted in a rapid souring of the reactor due to unbuffered volatile fatty acid (VFA) accumulation. The use of lime to control pH was unsatisfactory due to interference with the carbonate/bicarbonate equilibrium resulting in wide oscillations in the control parameter. The two stage system overcame the pH stability problems allowing stable operation for a period of 200 days without any requirement for pH control; this was attributed to the rapid flushing of VFA from the first stage reactor into the second stage, where efficient conversion to methane was established. Reactor performance was judged to be satisfactory with the breakdown of 53% of influent volatile solids. It was concluded that the reactor configuration of the two stage system offers the potential for the treatment of cellulosic wastes with a sub-optimal carbon to nitrogen ratio for conventional digestion.

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

State of the Art on Carbonic Anhydrase Modulators for Biomedical Purposes

2019 ◽  
Vol 26 (15) ◽  
pp. 2558-2573 ◽  
Author(s):  
Murat Bozdag ◽  
Abdulmalik Saleh Alfawaz Altamimi ◽  
Daniela Vullo ◽  
Claudiu T. Supuran ◽  
Fabrizio Carta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
State Of The Art ◽  
Cellular Level ◽  
Hydration Reaction ◽  
Carbonic Anhydrases ◽  
Crucial Importance ◽  
Learning Impairments ◽  
Current Review ◽  
Potential Use

The current review is intended to highlight recent advances in the search of new and effective modulators of the metalloenzymes Carbonic Anhydrases (CAs, EC 4.2.1.1) expressed in humans (h). CAs reversibly catalyze the CO2 hydration reaction, which is of crucial importance in the regulation of a plethora of fundamental processes at cellular level as well as in complex organisms. The first section of this review will be dedicated to compounds acting as activators of the hCAs (CAAs) and their promising effects on central nervous system affecting pathologies mainly characterized from memory and learning impairments. The second part will focus on the emerging chemical classes acting as hCA inhibitors (CAIs) and their potential use for the treatment of diseases.

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