*3.2. Metabolic Adaptations*

## 3.2.1. Oxygen Carriers and Storage

Due to its active metabolism and energy needs that require a high production of eggs, a determining factor in the biology of parasitic flatworms is the availability of oxygen, both in trematodes and in cestodes.

As a consequence of the low solubility of O2 in aqueous medium [64], some animals have developed a whole repertoire of respiratory pigments, which are metalloproteins and whose metallic element allows them to bind to O2 temporarily to transport it through the circulatory system and to distribute it in body tissues [65]. Thus, for example, mammals depend on myoglobin (Mb), a monomeric protein associated mainly with cardiac and skeletal muscle, and on hemoglobin (Hb), a tetrameric protein contained in erythrocytes; both present a coordinated iron atom in a tetrapyrrolic chemical structure [66].

Several homologues of myoglobins have been reported in vertebrates: androglobin (Adgb), neuroglobin (Ngb), globin X (GbX), myoglobin (Mb), and cytoglobin (Cygb) [67]. However, these present an unequal distribution among the groups of flatworms. In the case of the trematodes, *F. hepatica* and *P. westermani*, an Mb with a high affinity for O2 and a low *K*d, was initially described [68], similar to that reported in the nematode *Ascaris suum* [69,70]. In the case of cestodes, until 2002, Mb could be co-purified in the cysticercus of *T. solium*, possibly associated with muscle fibers of the subtegumental area [71]. Currently, through genomic and phylogenetic analyses, the presence of globins belonging to each of the GbX, Ngb, and Mb subfamilies was deduced in trematodes, whereas the cestode species had an Ngb-like single protein, and in turbellarians it was not possible to detect this subfamily, but the GbX and Mb-like proteins [72] were identified.

It is widely accepted that myoglobins, due to their high affinity for O2, function mainly as storage rather than for oxygen transport [73]. However, other additional functions have begun to be proposed for this type of molecule, such as reserves of the heme group (associated with egg production) or to serve as a ROS detoxifier [72]. For example, in the adult trematode *C. sinensis*, five different types of globins (CsMb 1–5) were identified, of which only CsMB-1 was found in the subtegumental area (parenchyma) and was the only one to respond to stimuli by exogenous O2, whereas the other globins were located exclusively in sexual organs and intrauterine eggs, which supports the participation of some globins in other specialized non-respiratory tasks.

Nevertheless, a high pO2 at the parasite's site does not necessarily imply that aerobic metabolism is present. An example of this is observed in *S. mansoni*, whose adult form lodges in the portal vein and whose metabolism has been reported to be preferably anaerobic, although this is not exclusive [74,75]. In contrast, the exceptionally high affinity for oxygen presented by the Hb of the fluke *Ophisthorchis viverrini* allows it to live in a practically anaerobic environment, such as the bile ducts [76].
