Search PubMed⌕ Search

Biomedical subjects

G Gacon

Publications and source records attributed to G Gacon.

At least 55 records · Page 3Linked to original sources
PubMed1980

[Polycythemia resulting from abnormal hemoglobin with increased affinity for oxygen. Two cases (author's transl)].

An abnormal hemoglobin with increased oxygen affinity has to be suspected in all the cases of polycythemia where no direct signs of "polycythemia vera", or any of the classical reasons for erythropoietic stimulation can be demonstrated. This fact is documented by two new observations, one concerning a 44 year-old man with Hb Kempsey, another concerning a 58 year-old woman with Hb Malmö. The diagnosis is based on a scrupulous electrophoretic study involving an isoelectric focusing on polyacrylamide gel, and, on the study of the oxygen binding properties of the red blood cells. This polycythemia being a compensatory mechanism allowing a normal oxygen delivery to the tissues has to be respected and a compromise must be found with the cardiovascular risk.

Adult↗
PubMed1980

Interaction between cytochrome b5 and hemoglobin: involvement of beta 66 (E10) and beta 95 (FG2) lysyl residues of hemoglobin.

In erythrocytes the reduction of oxidized hemoglobin (methemoglobin) is dependent upon an electron transport reaction between cytochrome b5 and methemoglobin. These two proteins are believed to form a complex whose bonding is principally determined by complementary charge interactions between acidic groups of cytochrome b5 and basic groups of hemoglobin. In order to refine this model, three surface lysyl hemoglobin variants--namely Hb N Baltimore beta 95 (FG2) Lys leads to Glu, Hb I Toulouse beta 66 (E10) Lys leads to Glu, and Hb I Philadelphia alpha 16 (A14) Lys leads to Glu--have been studied with respect to their reducibility and ability to bind cytochrome b5. In the two former variants, the substituted amino acids are located near the heme crevice; in the third one the substitution lies far from it. Substitutions of lysine for glutamic acid in positions beta 66 and beta 95 perturb the formation of the cytochrome b5--hemoglobin complex and result in a dramatic impairment of the cytochrome b5-mediated reduction, whereas the same mutation in position alpha 16 has no effect. We conclude that the lysine residues in positions beta 66 and beta 95 are directly involved in the binding of cytochrome b5. The three-dimensional structure of hemoglobin suggests that the cytochrome b5-binding domain of hemoglobin is constituted by four lysine residues surrounding the heme crevice in both alpha and beta chains. Similarities with other interacting hemoproteins are discussed.

Amino Acid Sequence↗
PubMed1980

Direct enzyme titration curve of NADH: cytochrome b5 reductase by combined isoelectric focusing/electrophoresis. Interactions between enzyme and cytochrome b5.

Methemoglobin reduction in human red cells involves successively an electron transport from NADH to a soluble form of cytochrome b5 (step 1) and from cytochrome b5 to methemoglobin (step 2). Step 1 is catalysed by an enzyme, soluble NADH:cytochrome b5 reductase (EC 1.6.2.2). Step 2 is non-enzymatic and involves complementary electrostatic interactions between acidic residues of cytochrome b5 and basic residues of hemoglobin [Gacon et al. (1980) Proc. Natl Acad. Sci. USA, 77, 1917-1921]. Here we present data indicating a similar mode of interactions occurring in step 1 between cytochrome b5 reductase and cytochrome b5. These results have been obtained by using the combined isoelectric focusing/electrophoresis method [Righetti et al. (1978) J. Chromatogr. 166, 455-460] allowing a direct titration of both entities either separately or in a mixture. This is the first report on the obtention of a direct titration curve of an enzyme visualized after specific staining (zymogram). The pH dependence of the Michaelis constant for cytochrome b5 is also in agreement with the hypothesis that electrostatic charges, which are maximal below pH 7.0, are essential in the interaction between cytochrome b5 and its reductase.

Animals↗
PubMed1978

[Hemoglobin Pyrgos beta 83 (EF 7) Gly leads to Asp in a Malian: structural identification and functional properties (author's transl)].

The second observation of hemoglobin Pyrogos is reported. This abnormality was initially described in a Greek family, in our case it concerns an African negro originating from the Republic of Mali. The abnormal hemoglobin was without clinical or hematological consequences. The structural defect is a substitution of an Asp for a Gly in the immediate vicinity of lysine beta 82. This leads to a large inhibition of the corresponding tryptic cleavage and therefore to difficulties in the determination of the mutation. A second feature is a slight modification occurring near one of the 2.3 DPG binding site. As a consequence, the regulatory effect of this organic phosphate is smaller in the purified and stripped component than on hemoglobin A.

Amino Acid Sequence↗
PubMed1977

Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala: isolation and functional properties of the heme saturated form.

Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala is a neutrally substituted unstable hemoglobin, exhibiting the same gross features as hemoglobin Köln beta98 (FG 5) Val leads to Met. In addition to the presence of a deheminized fraction, a heme saturated abnormal hemoglobin was visualized and isolated by high resolution electrofocusing. By functional studies of the fully heminized form, a slightly increased oxygen affinity, an impairment of heme-heme interaction and a decreased response to organic phosphates were demonstrated. These functional perturbations point out the importance of the beta98 invariant valyl residue, in the quaternary contacts. They can account for the poor oxygen delivery of erythrocytes.

Alanine↗
PubMed1977

[A new case of hemoglobin J Capetown alpha 92 (FG 4) Arg replaced by gln].

Hemoglobin J Capetown was found incidentally in a patient of french origin suffering from urticaria with delayed pressure oedema. Using a preparative finger-print technique, the structural determination was easy. A functional study of the purified component confirmed the high oxygen affinity of hemoglobin J Capetown and demonstrated a low reactivity for organic phosphates. These results may explain the perturbations observed in the whole blood.

Amino Acids↗