Kinetic mechanism of copper(II) transfer between the native sequence peptide representing the copper(II)-transport site of human serum albumin and L-histidine

The kinetics for Cu(II)-transfer reaction of the native sequence tripeptide, L-aspartyl-L-alanyl-L-histidine-N-methyl amide (AAHNMA), representing the Cu(II)-transport site of human serum albumin (HSA), and L-histidine (L-His) was studied in the forward and reverse reactions in a pH range 6.5–10.0 at I = 0.2 and 25°. For the Cu(II)-transfer from Cu(II)-L-His2 to native sequence peptide, the rate-determining step is a bond formation between Cu(II) and peptide nitrogen to form CuH−1AB from CuAB by deprotonation of peptide nitrogen atom, where A and B denote the anionic forms of AAHNMA and L-His, respectively. For the Cu(II)-transfer reaction from Cu(II)–peptide to L-His, the rate-determining step is a bond breaking between Cu(II) and peptide nitrogen to form CuAB fromCuH−1AB by protonation to a peptide nitrogen. The effect of carboxyl group of aspartyl residue in the native sequence peptide on the kinetic and equilibrium constants are discussed.

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Synthesis of the native copper(II)-transport site of human serum albumin and its copper(II)-binding properties

Biochemical Journal ◽

10.1042/bj1690061 ◽

1978 ◽

Vol 169 (1) ◽

pp. 61-69 ◽

Cited By ~ 50

Author(s):

K S Iyer ◽

S J Lau ◽

S H Laurie ◽

B Sarkar

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Low Ph ◽

Side Chain ◽

Complex Species ◽

Square Planar ◽

Native Sequence ◽

Ph Range ◽

Transport Site

A derivative of the native-sequence tripeptide of the specific Cu(II)-transport site of human serum albumin, L-aspartyl-L-alanyl-L-histidine N-methylamide, was synthesized, and its binding to Cu(II) was examined to determine the influence of the side-chain groups on the Cu(II) binding. The equilibria involved in the Cu(II)-L-aspartyl-L-alanyl-L-histidine N-methylamide system were investigated by analytical potentiometry. Three complex species were found in the pH range 4-10. The same species were identified in both the visible and circular-dichroism spectra. The main species present in the physiological pH range is shown to have the same ligands around the square-planar Cu(II) ion as those reported for albumin and tripeptides diglycyl-L-histidine and its N-methylamide derivative. The results obtained from competition experiments showed that this tripeptide has a higher affinity towards Cu(II) than has albumin itself. The overall findings are compared with those from albumin. At neutral pH the side chains do not play any important role in the Cu(II) binding, but at low pH the beta-carboxyl group of the N-terminal aspartic residue becomes important. A possible competition site on albumin for Cu(II) at low pH is discussed.

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Equilibrium and spectroscopic studies of the ternary system: L-histidine, copper(II), and the native sequence peptide representing the copper(II)-transport site of human serum albumin

Canadian Journal of Chemistry ◽

10.1139/v85-514 ◽

1985 ◽

Vol 63 (11) ◽

pp. 3117-3121 ◽

Cited By ~ 6

Author(s):

Masaaki Tabata ◽

Bibudhendra Sarkar

Keyword(s):

Human Serum Albumin ◽

Ternary System ◽

Serum Albumin ◽

Human Serum ◽

Spectroscopic Studies ◽

Mixed Ligand ◽

Anionic Form ◽

System L ◽

Native Sequence ◽

Transport Site

Equilibrium and spectroscopic studies of Cu(II)-transfer of native sequence tripeptide, L-aspartyl-L-alanyl-L-histidine-N-methyl amide (AAHNMA), representing the Cu(II)-transport site of human serum albumin (HSA), and L-histidine (L-His) are reported. The equilibria in the ternary system, M–A–B (M = Cu(II), A = anionic form of AAHNMA, and B = anionic form of L-His) have been investigated by analytical potentiometry in I = 0.2 [(Na+,H+) (Cl−,OH−)] at 25 °C. The ternary system shows the presence of five mixed ligand complexes: MH2AB, MHAB, MAB, MH−1AB, and MH−2AB. The species distribution and their stability constants were evaluated by the mathematical analysis of the potentiometric data. The species were further confirmed by their individual spectra computed from the absorption measurements. At physiological pH, the equilibrium studies reveal the presence of 13% of MH−1AB (λmax = 530 nm.ε = 90 M−1 cm−1) and 3% MAB (λmax = 595 nm, ε = 97 M−1 cm−1). The combined results of equilibrium and spectroscopic studies indicate the mixed ligand complex CuH−1AB formed by deprotonation of peptide nitrogen as an important intermediate in the Cu(II)-transfer reaction. The stability constant of CuH−1AB is compared to those of other tripeptides which were designed to mimic the specific Cu(II)-transport site of human albumin.

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Specific nickel(II)-transfer process between the native sequence peptide representing the nickel(II)-transport site of human serum albumin and L-histidine

Journal of Inorganic Biochemistry ◽

10.1016/0162-0134(92)80003-e ◽

1992 ◽

Vol 45 (2) ◽

pp. 93-104 ◽

Cited By ~ 15

Author(s):

Masaaki Tabata ◽

Bibudhendra Sarkar

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Transfer Process ◽

Native Sequence ◽

Transport Site

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Kinetic Studies of Copper(II)-exchange from L-Histidine to Human Serum Albumin and Diglycyl-L-histidine, a Peptide Mimicking the Copper(II)-transport Site of Albumin

Canadian Journal of Chemistry ◽

10.1139/v75-099 ◽

1975 ◽

Vol 53 (5) ◽

pp. 710-715 ◽

Cited By ~ 38

Author(s):

Show-Jy Lau ◽

Bibudhendra Sarkar

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Exchange Rates ◽

Human Serum ◽

Kinetic Studies ◽

Side Chain ◽

Exchange Reactions ◽

Equilibrium Study ◽

Rate Determining Step ◽

The Difference

The Cu(II)-exchange reactions of L-histidine with human serum albumin and diglycyl-L-histidine were studied at pH 7.53 in 0.1 MN-ethylmorpholine–HCl buffer. The exchange rates from L-histidine to albumin and peptide were determined as 0.67 and 0.42 s−1 respectively. Those from albumin and peptide to L-histidine were obtained as 0.04 and 0.07 s−1 respectively. This result is in accord with the earlier observations of the equilibrium study that the peptide has about half the Cu(II)-binding affinity as compared to albumin. The difference in the Cu(II)-exchange rates of albumin and peptide may reflect the influence of either the COOH-terminal free carboxyl group of the peptide or the side-chain residues of the Cu(II)-binding site in the native protein or both. An exchange mechanism is proposed in which the ternary complexes are shown to play the important role in the rate-determining step in the Cu(II)-exchange between a macromolecule and a small substance.

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The Effects of 1-Propanol on Behaviour of Human Serum Albumin in Alkaline Solution

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19930267 ◽

1993 ◽

Vol 58 (2) ◽

pp. 267-280

Author(s):

Vladimír Karpenko ◽

Rostislav Škrabana

Keyword(s):

Fatty Acids ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Transition ◽

Point Of View ◽

Uv Spectrophotometry ◽

Fourth Derivative ◽

Ph Range ◽

Albumin Molecule

The effects of 1-propanol ant to a certain extent of ethanol on human serum albumin were studied over the pH range 7 - 13.3 and alcohol concentrations up to 20 vol.%. In some case behaviour of the native preparation was compared with albumin cleared of weaker bound fatty acids. The data obtained by UV-spectrophotometry were discussed from the point of view of individual types of chromophores as well as in a broader context of the secondary structure. The results can be summarized as follows: (a) Partial removal of bound fatty acids has an influence on the dissociation of tyrosines. (b) The effect of alcohols on this dissociation is rather complex, the permitivity of the solvent being only a part of it. (c) At high alkaline pH a series of peaks in the fourth-derivative absorption spectra appear in the region 305 - 320 nm. These peaks were shown to correspond to buried dissociated tyrosines. (d) In the presence of 1-propanol a small conformational transition of albumin molecule is observed at pH below 9.

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