Root Effect Hemoglobin May Have Evolved to Enhance General Tissue Oxygen Delivery

Abstract

Holding Your Breath Hemoglobin and myoglobin are widely responsible for oxygen transport and storage (see the Perspective by Rezende ). The ability of diving mammals to obtain enough oxygen to support extended dives and foraging is largely dependent on muscle myoglobin (Mb) content. Mirceta et al. (p. 1303 ) found that in mammalian lineages with an aquatic or semiaquatic lifestyle, Mb net charge increases, which may represent an adaptation to inhibit self-association of Mb at high intracellular concentrations. Epistasis results from nonadditive genetic interactions and can affect phenotypic evolution. Natarajan et al. (p. 1324 ) found that epistatic interactions were able to explain the increased hemoglobin oxygen-binding affinity observed in deer mice populations at high altitude. In mammals, the offloading of oxygen from hemoglobin is facilitated by a reduction in the blood's pH, driven by metabolically produced CO 2 . However, in fish, a reduction in blood pH reduces oxygen carrying capacity of hemoglobin. Rummer et al. (p. 1327 ) implanted fiber optic oxygen sensors within the muscles of rainbow trout and found that elevated CO 2 levels in the water led to acidosis and elevated oxygen tensions.

Ecological Influences and Morphological Correlates of Resting and Maximal Metabolic Rates across Teleost Fish Species

“…Understanding the mechanistic basis of variation in RMR and MMR is also crucial for assessing how selection on these traits affects lower levels of biological organization (e.g., tissues and organs), which might in turn pave the way for the origin of new ecological niches and evolutionary innovations. For example, recent evidence that the Root effect enhances oxygen delivery to the muscles (Rummer et al 2013) suggests that the evolution of the swim bladder of ray-finned fishes may have resulted partly from selection for high aerobic capacity (Rezende 2013). …”

Dithiocarbamates with potent inhibitory activity against theSaccharomyces cerevisiaeβ-carbonic anhydrase

“…The starting amines (1a-21a) used to synthesize DTCs 1b-21b reported here (Scheme 1) included N,N-dimethylaminoethylenediamine 1a, aminoalcohols with three to five carbon atoms in their molecule 2a-4a, the bicyclic quinuclidine-3-amine (both the racemate as well as the R-and S-enantiomeric DTCs 5b-7b incorporating this scaffold were obtained), piperidine 8a and several of its derivatives with hydroxyl-, carboxy-, acetamido-and boc-amido functionalities in various positions of the heterocyclic ring, of types 9a-16a; morpholine and piperazine derivatives 17a-19a, as well as phenethylamine 20a and its sulfamoylated derivative, 4-aminoethylbenzenesulfonamide 21a, a well know CAI which binds to the enzyme through the sulfamoyl moiety 1,3 (Scheme 1). The choice of these scaffolds was motivated by the fact that the structure-activity relationship (SAR) for the inhibition of CAs with the DTCs reported earlier 7,8 was primarily influenced by the organic scaffold of the inhibitor. In fact, important differences of activity were observed between primary and secondary DTCs and between aliphatic or aromatic/ heterocyclic derivatives, respectively [40][41][42][43][44] .…”

“…The primary sulfonamides possessing the general formula RSO 2 NH 2 (where R may be an aromatic, heterocyclic or aliphatic moiety, but also an even smaller groups such as OH and NH 2 ) [1][2][3][4][5][6][7] dominated the landscape of carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) drug design for 70 years, since the discovery that such compounds inhibit the enzyme, in the 1940s [8][9][10][11][12][13][14][15] . However, recently, new important chemotypes with such properties emerged, by combining structure-based drug discovery strategies (X-ray crystallography and fragment-based drug design) with massive campaigns of screening vast library of compounds for detecting such an activity .…”

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

“…This metalloenzyme family is involved in numerous pathological and physiological processes in a different tissues and organs, including biosynthetic reactions, such as gluconeogenesis, lipid and urea synthesis, calcification, lipogenesis, ureagenesis, tumorigenicity, and the growth and virulence of various pathogens 1,3 . Furthermore, five distinct genetic families, the a-, b-, c-, dand z-CAs, are known to date, which constitute an interesting example of convergent evolution at the molecular level [5][6][7][8][9][10][11] . These five CA families vary in their preference for the catalytic metal ions used within the active site: for performing the catalysis: Zn ions are used by the above-mentioned five CA classes, whereas c-CAs most likely utilize Fe 2+ enzymes [12][13][14] .…”