The enigmatic oxygen‐avid hemoglobin of Ascaris

Abstract

The parasitic nematode Ascaris lives in the low-oxygen intestinal folds of over one billion people world-wide. The worm has an octameric hemoglobin that binds oxygen four orders of magnitude more tightly than does human hemoglobin. Our studies have focused on elucidating the molecular mechanism of oxygen avidity, the basis of multimerization and the function of this remarkable molecule. We now believe that we understand a fair amount about the molecular interactions that result in enhanced avidity, have some preliminary ideas on octamer formation, and have some hypotheses about possible function. Along the way we have stumbled into the disciplines of intron evolution, sterol biosynthesis and oxygen-regulated gene expression.

Flavohemoglobin Expression and Function in Saccharomyces cerevisiae

“…Membranes were prepared after mechanical disruption of the cells (45). 2 )-Low temperature spectra of whole cells of S. cerevisiae often have an absorption band near 575-577 nm which we attributed previously to porphyrins and Zn-porphyrins (46). We have now shown that this band is in fact due to the oxygenated form of the flavohemoglobin Yhb1p.…”

“…They all bind reversibly molecular oxygen, but their avidities vary greatly. The hemoglobin from the worm Ascaris binds oxygen 4 orders of magnitude more tightly than does human Hb (2). Some hemoglobins bind other molecules besides oxygen; the Hbs from the mollusc Lucina pectinata (3) and the deep-sea hydrothermal vent worm Riftia pachyptila (4) bind hydrogen sulfide and transport it to the sulfur-oxidizing bacterial symbionts which feed them.…”

Rice Hemoglobins (Gene Cloning, Analysis, and O2-Binding Kinetics of a Recombinant Protein Synthesized in Escherichia coli)

“…Appleby et al (1988) suggested that under normal aerobic conditions H b would be oxygenated, and that under O,-limiting conditions, deoxyferrous Hb levels would increase and trigger a n anaerobic response. Although O,-sensor heme proteins have been described i n other systems (Gilles-Gonzalez et al, 1991, 1995 Gilles-Gonzalez and Gonzalez, 1993), the above hypothesis was questioned recently by Andersson et al (1996), who suggest that Hbs may function as O, carriers i n metabolically active tissues.…”

“…However, under specific circumstances, such as in barley roots grown under microaerobic conditions, i n which high levels of Hb transcripts have been detected (Taylor e t al., 1994), nonsymbiotic Hbs may have other functions, including participation in the anaerobic response a n d possibly i n specific metabolic aspects of dedifferentiated tissues. Recently, a multitude of functions have been suggested for nonplant Hbs, which includes the transport of ligands other than O, (such as NO or CO), interaction with small organic molecules, O, scavenging, or formation of complexes with regulatory proteins (Gotz et al, 1994;Giardina et al, 1995;Goldberg, 1995;Jia et al, 1996). The pattern of expression of nonsymbiotic hb genes i n plants a n d the biochemical properties of the recombinant Hbs suggest that these proteins have other functions besides O, transport, which are yet to be determined.…”

Invertebrate hemoglobins and nitric oxide: How heme pocket structure controls reactivity

“…The most studied Hb of this type is that found within the perienteric fluid of the parasitic worm, Ascaris lumbricoides. This is an octameric Hb with each subunit possessing two globin domains, such that each molecule has sixteen potential heme binding sites [56,57]. It binds oxygen an extraordinary 25,000 times tighter than human Hb [58].…”