uman serum heme-albumin (HSA-heme-Fe) displays reactivity and spectroscopic properties similar to those of heme proteins. Here, the nitrite reductase activity of ferrous HSA-heme-Fe [HSA-heme-Fe(II)] is reported. The value of the second-order rate constant for the reduction of to NO and the concomitant formation of nitrosylated HSA-heme-Fe(II) (i.e., k (on)) is 1.3 M-1 s(-1) at pH 7.4 and 20 A degrees C. Values of k (on) increase by about one order of magnitude for each pH unit decrease between pH 6.5 to 8.2, indicating that the reaction requires one proton. Warfarin inhibits the HSA-heme-Fe(II) reductase activity, highlighting the allosteric linkage between the heme binding site [also named the fatty acid (FA) binding site 1; FA1] and the drug-binding cleft FA2. The dissociation equilibrium constant for warfarin binding to HSA-heme-Fe(II) is (3.1 +/- A 0.4) x 10(-4) M at pH 7.4 and 20 A degrees C. These results: (1) represent the first evidence for the reductase activity of HSA-heme-Fe(II), (2) highlight the role of drugs (e.g., warfarin) in modulating HSA(-heme-Fe) functions, and (3) strongly support the view that HSA acts not only as a heme carrier but also displays transient heme-based reactivity.

Ascenzi P, Tundo GR, Fanali G, Coletta M, & Fasano M. (2013). Warfarin modulates the nitrite reductase activity of ferrous human serum heme-albumin. JBIC, 18(8), 939-946 [10.1007/s00775-013-1040-2.].

Warfarin modulates the nitrite reductase activity of ferrous human serum heme-albumin.

ASCENZI, Paolo;
2013

Abstract

uman serum heme-albumin (HSA-heme-Fe) displays reactivity and spectroscopic properties similar to those of heme proteins. Here, the nitrite reductase activity of ferrous HSA-heme-Fe [HSA-heme-Fe(II)] is reported. The value of the second-order rate constant for the reduction of to NO and the concomitant formation of nitrosylated HSA-heme-Fe(II) (i.e., k (on)) is 1.3 M-1 s(-1) at pH 7.4 and 20 A degrees C. Values of k (on) increase by about one order of magnitude for each pH unit decrease between pH 6.5 to 8.2, indicating that the reaction requires one proton. Warfarin inhibits the HSA-heme-Fe(II) reductase activity, highlighting the allosteric linkage between the heme binding site [also named the fatty acid (FA) binding site 1; FA1] and the drug-binding cleft FA2. The dissociation equilibrium constant for warfarin binding to HSA-heme-Fe(II) is (3.1 +/- A 0.4) x 10(-4) M at pH 7.4 and 20 A degrees C. These results: (1) represent the first evidence for the reductase activity of HSA-heme-Fe(II), (2) highlight the role of drugs (e.g., warfarin) in modulating HSA(-heme-Fe) functions, and (3) strongly support the view that HSA acts not only as a heme carrier but also displays transient heme-based reactivity.
Ascenzi P, Tundo GR, Fanali G, Coletta M, & Fasano M. (2013). Warfarin modulates the nitrite reductase activity of ferrous human serum heme-albumin. JBIC, 18(8), 939-946 [10.1007/s00775-013-1040-2.].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/135047
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