Reduction of ferric haemoproteins by tetrahydropterins: a kinetic study

Abstract

We previously showed that one-electron transfer from tetrahydropterins to iron porphyrins is a very general reaction, with formation of an intermediate cation radical similar to the one detected in NO synthase. As a model reaction, the rates of reduction of eight haemoproteins by diMePH4 (6,7-dimethyltetrahydropterin) have been studied and correlated with their one-electron reduction potentials, E(m) (Fe(III)/Fe(II)). On the basis of kinetic data analyses, a bimolecular collisional mechanism is proposed for the electron transfer from diMePH4 to ferrihaemoproteins. Haemoproteins with reduction potentials below -160 mV were shown not to be reduced by diMePH4 to the corresponding ferrohaemoproteins. For haemoproteins with reduction potentials more positive than -160 mV, such as chloroperoxidase, cytochrome b5, methaemoglobin and cytochrome c, there was a good correlation between the second-order reduction rate constant and the redox potential, E(m) (Fe(III)/Fe(II)): [formula: see text]. The rate of reduction of cytochrome c by BH4 [(6R)-5,6,7,8-tetrahydrobiopterin] was determined to be similar to that of the reduction of cytochrome c by diMePH4. These results confirm the role of tetrahydropterins as one-electron donors to Fe(III) porphyrins.

Catalytic Reduction of a Tetrahydrobiopterin Radical within Nitric-oxide Synthase

“…1). The model is also consistent with the NOS heme and (estimated) H 4 B radical midpoint potentials (31)(32)(33), which indicate a strong positive driving force would exist for throughheme pterin radical reduction by the NOS flavoprotein domain.…”

“…We know that both events are CaMdependent and involve a one-electron transfer to an acceptor molecule that is bound within the NOS oxygenase domain. We know that the hydroquinone form of FMN (FMNH 2 ) reduces the NOS ferric heme (19,30), and thermodynamic considerations suggest the same probably holds for NOS pterin radical reduction (31)(32)(33). However, H 4 B is bound relatively far from the protein surface near the center of the NOSoxy dimer, whereas the bound heme has an edge placed within a few Angstroms of the protein surface (34).…”

Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection

“…However, with development of advanced rejection the increased levels of pterin synthesis were not maintained. In preliminary studies (unpublished observations), we confirmed in our mouse model of cardiac rejection that BH 4 levels increased in mouse allografts compared with nontransplanted donor heart controls, but this fell back below control levels in rejected allografts. This coincided with decreased GTPCH expression.…”

“…Synthesis of BH 4 is regulated by the expression of the key enzyme GTP cyclohydrolase I (GTPCH). The discovery of nuclear localization of GTPCH and other proteins involved in BH 4 synthesis (5) coupled with earlier findings that the mitogenic action of BH 4 in various cells is independent of changes in catecholamine and NO synthesis (1) suggests potentially new unknown roles of BH 4 . Thus there is new awareness of the potential regulation of GTPCH/BH 4 for a vast array of biological processes far beyond that regulating NO and catecholamine synthesis including cell proliferation, cell division, apoptosis, and immune function.…”

Characteristic Redox Potential-Time Curve in the Iron(II)/Nitric Acid Autocatalytic Reaction and Its Application to a Time Measurement-determination of Folic Acid

“…13,14 In other words, iron(II) is oxidized to iron(III) by the reaction of nitric acid, and it is reduced again to iron(II) by the tetrahydropterin frame of the tetrahydrofolate in the second reaction step. The second reaction step is impressed as Fe 3+ + ·FH4 2+ → Fe 2+ + FH4 3+ .…”