Enthalpic consequences of reduced chloride binding in Andean frog (Telmatobius peruvianus) hemoglobin

Abstract

Based on the exothermic nature of heme oxygenation, the O2 affinity of hemoglobin (Hb) decreases with increasing temperature, which may be physiologically advantageous in augmenting O2 unloading from blood in warm tissues with elevated metabolic rates. This negative oxygenation enthalpy (∆H (O)) may, however, become maladaptive, as in cold-tolerant ungulates where it may hamper O2 unloading in cold extremities and commonly is mitigated by an 'additional' chloride-binding site that decreases the temperature effect by increasing the endothermic release of Cl(-) ions upon O2 binding. Since no previous studies have focused on the consequences of reduced Cl(-) binding, I report and compare the enthalpic effects of chloride ions and the allosteric effector, ATP, on Hbs of the high-altitude aquatic Andean frog Telmatobius peruvianus that lacks the α-chain chloride-binding site, and the lowland (sub-)tropical frog Xenopus laevis that has retained this site and exhibits high chloride sensitivity. In contrast to Xenopus, Telmatobius Hb exhibits high temperature sensitivity (high negative ∆H') in the presence of Cl(-) ions, supporting the inverse relationship between the number of Cl(-)-binding sites and temperature sensitivity, and extending it to ectothermic vertebrates. The radically reduced chloride binding in Telmatobius Hb permits assessment of the enthalpy of ATP binding [(∆H' ≈ -62 kJ (mol ATP)(-1) at pH 7.0]-which contrasts sharply with previously reported increases in temperature sensitivity by ATP in toad (Bufo bufo) Hb. The high temperature sensitivity associated with decreased chloride binding and low phosphate sensitivity of Telmatobius Hb likely promotes cutaneous O2 uptake in cold, high-altitude ponds and streams.

High affinity and temperature sensitivity of blood oxygen binding inPangasianodon hypophthalmusdue to lack of chloride-hemoglobin allosteric interaction

“…⌬H O2 and ⌬H H2O are rather invariable across species; hence, the temperature sensitivity of O 2 binding is largely dependent on ⌬H cc and oxygenation-linked endothermic release of allosteric effectors (61). Therefore, a relationship exists between the number of binding sites for allosteric effectors and the temperature sensitivity of O 2 binding (8,60,62), where Hbs with multiple binding sites have a low temperature sensitivity, and vice versa. It has been suggested that the higher number of effector binding sites and, thus, low temperature sensitivity of O 2 binding, is beneficial in regionally heterothermic animals, where O 2 unloading can for example, be safeguarded to the extremities of Arctic mammals (7,8,15), and where O 2 delivery can be regulated to warm brains and swimming muscles of tuna, shark, and billfishes (9,31,62).…”

Enthalpic partitioning of the reduced temperature sensitivity of O2 binding in bovine hemoglobin

“…at Lys8β, Lys76β, His77β), given the evidence that yet other amino groups within the central cavity of bovine Hb (including Lys103β that is at a homologous position to Arg104β of human Hb) may be considered functional Cl − -binding sites (Ueno and Manning, 1992). Regardless, the negative correlation between the overall number of Cl − -binding sites and the temperature sensitivity of Hb-O 2 affinity remains valid, and is supported -and extended to lower vertebrates -by the distinctly higher temperature dependence of O 2 affinity encountered in Andean frog Telmatobius peruvianus Hb that lacks the α-chain Cl − -binding site, compared to that found in lowland toad Xenopus laevis Hb that has retained this Cl − -binding site (Weber, 2014).…”

A new early water frog (Telmatobius) from the Miocene of the Bolivian Altiplano

“…2017; Muñoz‐Saravia 2018), as well as to enduring low oxygen levels and pronounced temperature fluctuations (Hutchison et al . 1976; Weber 2014; Muñoz‐Saravia et al . 2018).…”

“…The genus name Telmatobius, as their common name (Water frogs), alludes to their mostly aquatic habits in a variety of environments, including mountain streams of temperate humid realms such as cloud forests, as well as streams, ponds, peat bogs, thermal springs, and lakes of the colder and drier highlands of the Altiplano and Puna (Vellard 1951;De la Riva 2005;Barrionuevo 2017). The aquatic highland species adapted to the harsh conditions of highland environments (Vellard 1951;Sáez et al 2022), such as the endangered Titicaca Water Frog (Telmatobius culeus; IUCN SSC Amphibian Specialist Group 2020), show morphological, physiological, and ecological peculiarities related to feeding and communicating underwater Brunetti et al 2017;Muñoz-Saravia 2018), as well as to enduring low oxygen levels and pronounced temperature fluctuations (Hutchison et al 1976;Weber 2014;Muñoz-Saravia et al 2018).…”