The effect of organic phosphates on the reactions of haemoglobin and oxyhaemoglobin (carboxyhaemoglobin) with carbon dioxide

Pace, Mario; Rossi-Bernardi, L.; Roughton, F. J. W.

doi:10.1042/bj1190067p

Cited by 16 publications

(7 citation statements)

References 4 publications

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“…Table III shows the results obtained when oxygen absorption by hemoglobin was measured in the presence of carbon dioxide with and without benzenepentacarboxylate in solution. It appeared that the combined action of benzenepentacarboxylate and C02 was far from being the sum of the separate effects, in a way similar to that reported for 2,3-diphosphoglycerate and C02 (Bauer, 1969;Pace et al, 1970;Tomita and Riggs, 1971;Brenna et al, 1972). This suggests a competition between C02 and benzenepentacarboxylate similar to that shown between C02 and 2,3-diphosphoglycerate.…”

Section: Interaction Of Benzenepentacarboxylate With Human Fetalmentioning

confidence: 51%

“…The competition between 2,3-diphosphoglycerate and C02 (Bauer, 1969;Brenna et al, 1972;Pace et al, 1970;Tomita and Riggs, 1971) is generally taken as a strong support for the hypothesis that the 1/3-valines participate in the binding of 2,3-diphosphoglycerate. The similar competition between benzenepentacarboxylate and C02 would suggest that these groups interact also with benzenepentacarboxylate.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Allosteric effectors of hemoglobin. Interaction of human adult and fetal hemoglobins with poly(carboxylic acids)

Shimizu¹,

Bucci²

1974

Biochemistry

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Aliphatic and aromatic poly(carboxylic acids) interacted with hemoglobin lowering its oxygen affinity. The magnitude of the effect appeared unrelated to the structure of the polyacids and proportional to the number of carboxyl groups present in the compounds. The largest effect was produced by benzenepentacarboxylic acid which at 20°in 0.05 m bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane buffer at pH 7.3 increased log Fy, of human adult hemoglobin from about 0.3 to ca. 1.10 and that of human fetal hemoglobin from ca. 0.5 to ca. 0.95. Its affinity for fetal hemoglobin appeared less than that for adult hemoglobin. It increased the Bohr effect of both hemoglobins, indicating the release, in its presence, of extra protons in addition to those of the alkaline T A he models proposed by Perutz (1970) and Arnone (1972) for the interaction of 2,3-diphosphoglycerate with human hemoglobin show that the 1/3-valines, the 143/3-histidines, and one of the 82/3-lysines form salt bridges with the five negative charges of 2,3-diphosphoglycerate. The 82/3-lysine would interact with the carboxyl group of 2,3-diphosphoglycerate and, according to Arnone (1972), the 2/3-histi dines can also participate in the binding, in this case substituting the 1/3valines. These groups are present in a crevice, between the two ß chains, which only in deoxyhemoglobin is large enough to accommodate 2,3-diphosphoglycerate, thus explaining the preferential binding of 2,3-diphosphoglycerate to this form of hemoglobin (Perutz, 1970).The electrostatic interaction is bound to modify the proton binding behavior of the groups involved, increasing the pK of the positive charges and decreasing that of the negative groups, so that within certain pH ranges hemoglobin is expected to absorb protons upon interaction with 2,3-diphosphoglycerate. This phenomenon contains much information. As it will be discussed in another manuscript, it might help to measure the affinity constant of the effector for hemoglobin, the number of groups which in hemoglobin participate in the interaction, their pK, and their shift to higher pK values in the presence of 2,3-diphosphoglycerate.

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Section: Interaction Of Benzenepentacarboxylate With Human Fetalmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 98%

Allosteric effectors of hemoglobin. Interaction of human adult and fetal hemoglobins with poly(carboxylic acids)

Shimizu¹,

Bucci²

1974

Biochemistry

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“…We have shown that CO2 can also bind at the two N-terminal amino groups of the ,B-chains, and a competition between 2,3-diphosphoglycerate and C02 is to be expected. Such an interaction was first demonstrated by Bauer (1969) and later quantitatively investigated by Pace, Rossi-Bernardi & Roughton (1970). By determining the total C02 in solutions of human oxy-and deoxy-haemoglobin at constant pCO2 at 370C in the presence of a ratio of up to 2mol of ATP or 2,3-diphosphoglycerate/mol of haemoglobin tetramer, Pace et al (1970) showed that organic phosphate molecules decreased the total amount of C02 bound by deoxyhaemoglobin by 25% whereas the total C02 bound by oxyhaemoglobin was not affected.…”

Section: J V Kilmartin and L Rossi-bernardimentioning

confidence: 77%

The binding of carbon dioxide by horse haemoglobin

Kilmartin

Rossi-Bernardi²

1971

Biochemical Journal

157

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1. Three modified horse haemoglobins have been prepared: (i) alpha(c) (2)beta(c) (2), in which both the alpha-amino groups of the alpha- and beta-chains have reacted with cyanate, (ii) alpha(c) (2)beta(2), in which the alpha-amino groups of the alpha-chains have reacted with cyanate, and (iii) alpha(2)beta(c) (2), in which the two alpha-amino groups of the beta-chain have reacted with cyanate. 2. The values of n (the Hill constant) for alpha(c) (2)beta(c) (2), alpha(2)beta(c) (2) and alpha(c) (2)beta(2) were (respectively) 2.5, 2.0 and 2.6, indicating the presence of co-operative interactions between the haem groups for all derivatives. 3. In the alkaline pH range (about pH8.0) all the derivatives show the same charge as normal haemoglobin whereas in the acid pH range (about pH6.0) alpha(c) (2)beta(c) (2) differs by four protonic charges and alpha(c) (2)beta(2), alpha(2)beta(c) (2) by two protonic charges from normal haemoglobin, indicating that the expected number of ionizing groups have been removed. 4. alpha(c) (2)beta(2) and alpha(c) (2)beta(c) (2) show a 25% decrease in the alkaline Bohr effect, in contrast with alpha(2)beta(c) (2), which has the same Bohr effect as normal haemoglobin. 5. The deoxy form of alpha(c) (2)beta(c) (2) does not bind more CO(2) than the oxy form of alpha(c) (2)beta(c) (2), whereas alpha(c) (2)beta(2) and alpha(2)beta(c) (2) show intermediate binding. 6. The results reported confirm the hypothesis that, under physiological conditions, haemoglobin binds CO(2) through the four terminal alpha-amino groups and that the two terminal alpha-amino groups of alpha-chains are involved in the Bohr effect.

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“…This was unequivocally shown to be true by Rossi-Bernardi & Roughton (1967) who furthermore gave ample theoretical evidence that the formation of carbamate occurs at the N-terminal amino groups of both a-and ,-chains which was later experimentally verified by Kilmartin & Rossi-Bernardi (1969. From studies in haemoglobin solutions to which organic phosphates have been added it was inferred that the actual difference between the amount of carbon dioxide bound to oxygenated and deoxygenated haemoglobin (AHbCO2/AHbO2) is less than that assumed by Rossi-Bernardi & Roughton (1967), most likely due to an interaction of these substances and carbon dioxide at the terminal amino groups of the fl-chains (Bauer, 1969(Bauer, , 1970Pace et al 1970;Siggaard-Andersen, 1971;Tomita & Riggs, 1971). The value of -AHbCO2/AHbO2 = 0081 at 370C, pCO2 = 40 mm Hg and 464 CARBAMA TE CONTENT OF HUMAN ERYTHROCYTES 465 a red cell pH of 7-2 obtained in the present study (Fig.…”

Section: Resultsmentioning

confidence: 93%

“…Later on it was demonstrated that 2,3-DPG not only decreases the oxygen affinity of haemoglobin but also its carbon dioxide affinity, i.e. the formation of carbamate (Bauer, 1969(Bauer, , 1970Pace, Rossi-Bernardi & Roughton 1970;Tomita & Riggs, 1971;Siggaard-Andersen, 1971). It thus became evident that the amount of carbamate formed at the haemoglobin molecule not only depends upon pH, PCO2 and oxygen saturation but also on the concentration of organic phosphate esters normally present in the red cell.…”

Section: Introductionmentioning

confidence: 99%