EFFECTS OF HEME IRON LIGANDS ON SELF-ASSOCIATION OF βSH CHAINS

Cooperative ligand binding by tetrameric vertebrate hemoglobins (Hbs) makes possible the delivery of oxygen at higher pressures than would otherwise occur. This cooperativity depends on changes in dimer-dimer interactions within the tetramer and is reflected in a 50 000-fold increase in the tetramer-dimer dissociation constant in human Hb upon oxygenation at pH 7.4, from approximately 2x10(-11)mol l-1 to approximately 10(-6)mol l-1. Hbs that undergo such ligand-dependent changes in association are widespread in non-vertebrates, where the mechanisms are very different from those in vertebrates. Oligomeric Hbs have been identified in organisms in five phyla (molluscs, echinoderms, annelids, phoronids and chordates) that dissociate to subunits upon oxidation of the heme iron and reassociate with the binding of ferric iron ligands such as CN-, N3- or NO2-. Thus, the valence and ligand state of the heme iron control the stability of a critical subunit interface. The broad distribution of this phenomenon suggests a common mechanism of communication between heme and interface that may be almost universal among non-vertebrate Hbs. This interaction may be similar to that known for the homodimeric Hb of the mollusc Scapharca inaequivalvis. Although muscle tissue Hbs or myoglobins (Mbs) are usually monomeric, with non-cooperative O2 binding, the radular muscles of gastropod molluscs and chitons have homodimeric Mbs that bind O2 cooperatively. Cooperative non-muscle tissue Hbs have also been identified. These include the neural Hb of the nemertean worm Cerebratulus lacteus and the Hb of the diving beetle Anisops assimilis, which exhibit deoxygenation-dependent self-association of monomers that is associated with high Hill coefficients. Calculations suggest that the 2-3 mmol l-1 concentration of Hb on a heme basis in the brain of Cerebratulus should substantially extend the time as an active predator in an anaerobic or hypoxic environment. Oxygen from the Hb of Anisops is delivered to a gas bubble and thereby controls the buoyant density. Many Hbs of amphibians, reptiles, birds and some embryonic mammals exhibit a further 'supercooperativity' of O2 binding which depends on reversible deoxygenation-dependent tetramer-tetramer association to form an assemblage with a very low affinity for O2. This phenomenon results in steeper O2-binding curves than exhibited by tetramers alone. The increased cooperativity should result in an increase in the amount of O2 delivered to the tissues and should be especially valuable for avian flight muscles.

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Dietary Heme Iron does not Prevent Postgastrectomy Anemia but Fructooligosaccharides Improve Bioavailability of Heme Iron in Rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.69.5.348 ◽

1999 ◽

Vol 069 (05) ◽

pp. 0348-0355 ◽

Cited By ~ 20

Author(s):

A. Ohta ◽

K. Sakai ◽

M. Takasaki ◽

M. Uehara ◽

T. Tokunaga ◽

...

Keyword(s):

Heme Iron

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Meat and Meat Products Consumption in Italy: Contribution to Trace Elements, Heme Iron and selected B Vitamins supply

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.74.4.247 ◽

2004 ◽

Vol 74 (4) ◽

pp. 247-251 ◽

Cited By ~ 13

Author(s):

Lombardi-Boccia ◽

Lanzi ◽

Lucarini ◽

Di Lullo

Keyword(s):

Trace Elements ◽

Daily Intake ◽

Meat Products ◽

Heme Iron ◽

B Vitamins ◽

Zinc Intake ◽

Consumption Frequency ◽

Iron And Zinc ◽

Iron Heme ◽

Daily Intakes

This study was undertaken to estimate the contribution of meat and meat products consumption to the daily intakes of trace elements (Fe, Zn, Cu, Se), heme iron, and selected B vitamins (thiamine, riboflavin, niacin) in Italy. Meat and meat products were selected on the basis of their consumption frequency reported by the most recent nationwide dietary individual survey carried out in Italy (INN-CA study). The daily intakes of total iron and heme iron were 1.65 and 1.13 mg/person/day. Zinc intake was 3.65 mg/person/day. Beef made the main contribution to iron, heme iron, and zinc daily intakes. Copper daily intake was 107.3 mug/person/day, with meat products provided the highest contribution (40 mug/person/day). Daily intake of selenium (7.14 mug/person/day) was provided mainly by poultry consumption. Thiamine intake was 228 mug/person/day, and meat products were the main source (110 mug/person/day). Riboflavin intake was 136 mug/person/day, with both beef and meat products as the main contributors (40 mug/person/day). Niacin intake was 7.53 mg/person/day, and poultry was the main source (2.28 mg/person/day). Meat and meat products were a valuable source of micronutrients, supplying 47, 48, and 24% of zinc, niacin, and thiamin daily requirements, respectively, and over 10% of iron, copper, selenium, and riboflavin daily average requirement values of the italian RDAs calculated for the population involved in the survey (INN-CA study).

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Aggregated, Conformationally Changed Fibrinogen Exposes the Stimulating Sites for t-PA-Catalysed Plasminogen Activation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650269 ◽

1996 ◽

Vol 75 (02) ◽

pp. 326-331 ◽

Cited By ~ 7

Author(s):

Unni Haddeland ◽

Knut Sletten ◽

Anne Bennick ◽

Willem Nieuwenhuizen ◽

Frank Brosstad

Keyword(s):

Conformational Changes ◽

Gel Permeation Chromatography ◽

Tissue Type ◽

Plasminogen Activation ◽

Chromogenic Substrate ◽

Type Plasminogen Activator ◽

Gel Permeation ◽

Self Association ◽

Fibrin Monomers ◽

Stimulation Of

SummaryThe present paper shows that conformationally changed fibrinogen can expose the sites Aα-(148-160) and γ-(312-324) involved in stimulation of the tissue-type plasminogen activator (t-PA)-catalysed plasminogen activation. The exposure of the stimulating sites was determined by ELISA using mABs directed to these sites, and was shown to coincide with stimulation of t-PA-catalysed plasminogen activation as assessed in an assay using a chromogenic substrate for plasmin. Gel permeation chromatography of fibrinogen conformationally changed by heat (46.5° C for 25 min) demonstrated the presence of both aggregated and monomeric fibrinogen. The aggregated fibrinogen, but not the monomeric fibrinogen, had exposed the epitopes Aα-(148-160) and γ-(312-324) involved in t-PA-stimulation. Fibrinogen subjected to heat in the presence of 3 mM of the tetrapeptide GPRP neither aggregates nor exposes the rate-enhancing sites. Thus, aggregation and exposure of t-PA-stimulating sites in fibrinogen seem to be related phenomena, and it is tempting to believe that the exposure of stimulating sites is a consequence of the conformational changes that occur during aggregation, or self-association. Fibrin monomers kept in a monomeric state by a final GPRP concentration of 3 mM do not expose the epitopes Aα-(148-160) and γ-(312-324) involved in t-PA-stimulation, whereas dilution of GPRP to a concentration that is no longer anti-polymerizing, results in exposure of these sites. Consequently, the exposure of t-PA-stimulating sites in fibrin as well is due to the conformational changes that occur during selfassociation.

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Self-association of insulin. Its pH dependence and effect of plasma

Diabetes ◽

10.2337/diabetes.36.3.261 ◽

1987 ◽

Vol 36 (3) ◽

pp. 261-264 ◽

Cited By ~ 15

Author(s):

E. Helmerhorst ◽

G. B. Stokes

Keyword(s):

Ph Dependence ◽

Self Association

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Strongly Coupled Redox-Linked Conformational Switching at the Active Site of the Non-Heme Iron-Dependent Dioxygenase, TauD

10.26434/chemrxiv.9461462 ◽

2019 ◽

Author(s):

Christopher John ◽

Greg M. Swain ◽

Robert P. Hausinger ◽

Denis A. Proshlyakov

Keyword(s):

Active Site ◽

Structural Model ◽

Heme Iron ◽

Chemical Transformations ◽

Experimental Conditions ◽

Strongly Coupled ◽

Non Heme Iron ◽

Reversible Redox ◽

Wide Range ◽

Complex Structural

2-Oxoglutarate (2OG)-dependent dioxygenases catalyze C-H activation while performing a wide range of chemical transformations. In contrast to their heme analogues, non-heme iron centers afford greater structural flexibility with important implications for their diverse catalytic mechanisms. We characterize an <i>in situ</i> structural model of the putative transient ferric intermediate of 2OG:taurine dioxygenase (TauD) by using a combination of spectroelectrochemical and semi-empirical computational methods, demonstrating that the Fe (III/II) transition involves a substantial, fully reversible, redox-linked conformational change at the active site. This rearrangement alters the apparent redox potential of the active site between -127 mV for reduction of the ferric state and 171 mV for oxidation of the ferrous state of the 2OG-Fe-TauD complex. Structural perturbations exhibit limited sensitivity to mediator concentrations and potential pulse duration. Similar changes were observed in the Fe-TauD and taurine-2OG-Fe-TauD complexes, thus attributing the reorganization to the protein moiety rather than the cosubstrates. Redox difference infrared spectra indicate a reorganization of the protein backbone in addition to the involvement of carboxylate and histidine ligands. Quantitative modeling of the transient redox response using two alternative reaction schemes across a variety of experimental conditions strongly supports the proposal for intrinsic protein reorganization as the origin of the experimental observations.

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