The binding of pyridoxal 5′-phosphate to human serum albumin

Fonda, Margaret L.; Trauss, Christiane; Guempel, Ulrike M.

doi:10.1016/0003-9861(91)90167-h

Cited by 35 publications

(23 citation statements)

References 25 publications

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“…Sequence differences in the PLP binding sites of HSA (Lys"") and BSA (L~s"~'""~) [S] support previous results which demonstrated differences in PLP binding to these albumins [3].…”

Section: Discussionsupporting

confidence: 84%

“…the binding of PLP to HSA, but do inhibit FLP binding to BSA [3]. Pyridoxal phosphate (PLP), the major cofactor form of vitamin B6, is required in many of the reactions of amino acid metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…Since PLP bound to HSA is protected from hydrolysis by phosphatases [ 121, HSA serves as a reservoir and mediates PLP transport to tissues. Although PLP binds as a Schiff base to both BSA and HSA, recent studies suggest that PLP binds differently to HSA than it does to BSA [3]. Equilibrium binding data indicate a single high affinity and two or more nonspecific sites for PLP in HSA [3], In previous studies, PLP was shown to be localized to a region of HSA containing residues 162-197, but sequencing was not performed [4].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Lys¹⁹⁰ as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

1992

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The covalent binding of pyridoxal5'-phosphate (PLP) to human serum albumin (HSA) is important in the regulation of PLP metabolism. In plasma, PLP is bound to HSA at a single high-affinity and at two or more nonspecific sites. To characterize the primary PLP binding site, HSA was incubated with ['HIPLP, and the Schiff base linkage was reduced with potassium borohydride. Tryptic peptides were purified, and the major labeled peptide was sequenced. Amino acid analysis confirmed a homogeneous peptidc Leu-Asp-Glu-Lcu-Arp-As~GIu-Gly-Xaa-Als-Ser-Ser-Ala-Lys which corresponds to residues 182-195 of HSA. The data indicate that LyslYo is the primary PLP binding site. This Lys residue is distinct from other sites of covalent adduct formation; namely, the primary sites for nonenzymatic glycosylation (LysJz5) and acctyla.tion by aspirin (L~s'~~).Pyridoxal 5'.phosphate; Vitamin B6; Binding site; Albumin (human)

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“…Sequence differences in the PLP binding sites of HSA (Lys"") and BSA (L~s"~'""~) [S] support previous results which demonstrated differences in PLP binding to these albumins [3].…”

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Lys¹⁹⁰ as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

1992

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“…Because PLP bound to HSA is protected from hydrolysis by phosphorylases (43), HSA functions as a reservoir and mediates PLP transport to tissues. Binding sites for PLP in HSA have been identified as Lys 190 , which has a high affinity, and are composed of two or more nonspecific residues (39,44). We concluded that serum albumin detached PLP, which was coupled with the q-amino group at Lys 211 via a Schiff 's base of holoenzyme in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 90%

“…Fonda et al (39) reported that oleic acid inhibited the binding of PLP to serum albumins. To prevent reduction of the actual enzyme activity of PEG-METase in contact with serum albumins, we investigated the effect of addition of PLP and potassium oleate to the mixtures.…”

Section: Resultsmentioning

confidence: 99%

Physicochemical and Pharmacokinetic Characterization of Highly Potent Recombinant l-Methionine γ-Lyase Conjugated with Polyethylene Glycol as an Antitumor Agent

et al. 2006

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A highly potent recombinant L-methionine ;-lyase (METase) conjugated with polyethylene glycol (PEG) was characterized physicochemically and pharmacokinetically in vivo and in vitro. Pegylated METase (PEG-METase), which contains pyridoxal 5V-phosphate (PLP) as a cofactor in the molecule, is a potent anticancer agent that can deplete L-methionine from plasma. Although pegylation decreased its specific activity, dithiothreitol (DTT) treatment increased it over three times with the detachment of one PEG moiety modified with a cysteine residue. We can produce DTT-treated PEG-METase on a large scale in sufficient quality for therapeutic use. The superiority of DTT-treated PEG-METase was confirmed by the enhancement of L-methionine depletion and amelioration of pharmacokinetics in mice. The holoenzyme of DTT-treated PEG-METase gave a several times larger area under the plasma concentration curve than that of DTT-untreated PEGMETase, not because of an increase of the half-life but because of high specific activity. Conversely, simultaneous PLP infusion led to a greatly increased half-life of the holoenzyme. DTT-treated PEG-METase administration with PLP infusion was the most useful combination for maximizing the potency of the enzyme. We showed that serum albumin interfered with holoenzyme activity in vitro. The decrease of holoenzyme activity was dependent on the type of serum albumin. We concluded that PLP was released from PEG-METase by serum albumin in vivo and in vitro. The deleterious effect of PLP dissociation from PEG-METase could be improved by supplementing PLP and oleic acid. Their synergistic effect in preventing a decrease of the holoenzyme activity was also

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Synthesis of a Fluorogenic Analogue of Sphingosine‐1‐Phosphate and Its Use to Determine Sphingosine‐1‐Phosphate Lyase Activity

et al. 2009

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The binding of pyridoxal 5′-phosphate to human serum albumin

Cited by 35 publications

References 25 publications

Identification of Lys¹⁹⁰ as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

Identification of Lys¹⁹⁰ as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

Physicochemical and Pharmacokinetic Characterization of Highly Potent Recombinant l-Methionine γ-Lyase Conjugated with Polyethylene Glycol as an Antitumor Agent

Synthesis of a Fluorogenic Analogue of Sphingosine‐1‐Phosphate and Its Use to Determine Sphingosine‐1‐Phosphate Lyase Activity

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The binding of pyridoxal 5′-phosphate to human serum albumin

Cited by 35 publications

References 25 publications

Identification of Lys190 as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

Identification of Lys190 as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

Physicochemical and Pharmacokinetic Characterization of Highly Potent Recombinant l-Methionine γ-Lyase Conjugated with Polyethylene Glycol as an Antitumor Agent

Synthesis of a Fluorogenic Analogue of Sphingosine‐1‐Phosphate and Its Use to Determine Sphingosine‐1‐Phosphate Lyase Activity

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Identification of Lys¹⁹⁰ as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin

Identification of Lys¹⁹⁰ as the primary binding site for pyridoxal 5′‐phosphate in human serum albumin