Enzyme iron-dependent

Tyrosine hydroxylase (TH) is an enzyme that catalyzes the hydroxylation of tyrosine to 3,4-dihydroxypheny-lalanine in the brain and adrenal glands. TH is the rate-limiting enzyme in the biosynthesis of dopamine. This non-heme iron-dependent monoxygenase requires the presence of the cofactor tetrahydrobiopterin to maintain the metal in its ferrous state. 

More recently, another series of di-r-butyl phenol antioxidants represented by LY231617 has been developed. These compounds inhibit iron-dependent lipid j>eroxidation and antagonize hydrogen peroxide-induced cortical neuronal injury [at 5 /iM LY231617 increased neuron viability fiom 20% (untreated) to 70%]. Interestingly, LY231617 does not inhibit the key enzymes of... 

This emphasizes that iron(II) complexes bearing more bulky bis(pyrazol-l-yl)acetate ligands should be good structural models to mimic mononuclear non-heme iron dependent enzymes. 

Many proteins, including many enzymes, contain hghtly bound metal ions. These may be inhmately involved in enzyme catalysis or may serve a purely structural role. The most common tightly bound metal ions found in metalloproteins include copper (Cu+ and Cu +), zinc (Zn +), iron (Fe + and Fe +), and manganese (Mn +). Other proteins may contain weakly bound metal ions that generally serve as modulators of enzyme activity. These include sodium (Na+), potassium (K+), calcium (Ca +), and magnesium (Mg +). There are also exotic cases for which enzymes may depend on nickel, selenium, molybdenum, or silicon for activity. These account for the very small requirements for these metals in the human diet. 

Iron-sulfur clusters (7) occur as prosthetic groups in oxidoreductases, but they are also found in lyases—e.g., aconitase (see p. 136) and other enzymes. Iron-sulfur clusters consist of 2-4 iron ions that are coordinated with cysteine residues of the protein (-SR) and with anorganic sulfide ions (S). Structures of this type are only stable in the interior of proteins. Depending on the number of iron and sulfide ions, distinctions are made between [Fe2S2], [Fe3S4], and [Fe4S4] clusters. These structures are particularly numerous in the respiratory chain (see p. 140), and they are found in all complexes except complex IV. 

This iron-dependent enzyme [EC 1.13.11.2], also called metapyrocatechase, catalyzes the reaction of catechol with dioxygen to produce 2-hydroxymuconate semialdehyde. The enzyme from Alcaligenes sp. strain 0-1 reportedly catalyzes the reaction of 3-sulfocatechol with dioxygen and water to produce (2E,4Z)-2-hydroxymuconate and bisulfite. 

This enzyme [EC 1.13.11.15], also called homoprotoca-techuate 2,3-dioxygenase, is an iron-dependent enzyme... 

This iron-dependent enzyme [EC 1.13.11.4] catalyzes the following reaction 2,5-dihydroxybenzoate + 02 = maleylpyruvate. 

This enzyme [EC 1.13.11.5], an iron-dependent system (also called homogentisicase and homogentisate oxygenase), catalyzes the reaction of homogentisate with dioxygen to produce 4-maleylacetoacetate. 

This iron-dependent enzyme [EC 1.13.11.34], better known as arachidonate 5-lipoxygenase and occasionally referred to as leukotriene A4 synthase, catalyzes the reaction of arachidonate with dioxygen to produce (6 , 8Z,1 lZ,14Z)-(5S)-5-hydroperoxyicosa-6,8,ll, 14-tetraenoate, which rapidly converts to leukotriene A4. 

This iron-dependent enzyme [EC 1.14.16.6], also known as L-mandelate 4-hydroxylase, catalyzes the reaction of (5)-2-hydroxy-2-phenylacetate with tetrahydropteridine and dioxygen to produce (5)-4-hydroxymandelate, dihy-dropteridine, and water. 

This iron-dependent enzyme [EC 4.2.1.35], also known as citraconase and citraconate hydratase, catalyzes the conversion of (R)-2-methylmalate to 2-methylmaleate and water. 

This enzyme [EC 1.5.1.13], also known as nicotinate hydroxylase, catalyzes the reaction of nicotinate with NADP+ and water to produce 6-hydroxynicotinate and NADPH. This iron-dependent flavoprotein will also oxidize NADPH. 

Nitrite reductase (NAD(P)H) [EC 1.6.6.4] catalyzes the reaction of three NAD(P)H with nitrite to yield three NAD(P)+, NH4OH, and water. Cofactors for this enzyme include FAD, non-heme iron, and siroheme. (2) Nitrite reductase (cytochrome) [EC 1.7.2.1] is a copper-depen-dent system that catalyzes the reaction of nitric oxide with two ferricytochrome c and water to produce nitrite and two ferrocytochrome c. (3) Ferredoxin-nitrite reductase [EC 1.7.7.1], a heme- and iron-dependent enzyme, catalyzes the reaction of ammonia with three oxidized ferredoxin to produce nitrite and three reduced ferredoxin. (4) Nitrite reductase [EC 1.7.99.3] is a copper- and FAD-dependent enzyme that catalyzes the reaction of two nitric oxide with an acceptor substrate and two water to produce two nitrite and the reduced acceptor. 

Sulfite reductase (NADPH) [EC 1.8.1.2] catalyzes the reaction of H2S with three NADP+ and three water molecules to produce sulfite and three NADPH. The enzyme requires FAD, FMN, and heme. Sulfite reductase (ferre-doxin) [EC 1.8.7.1] catalyzes the iron-dependent reaction of H2S with three oxidized ferredoxin and three water to produce sulfite and three reduced ferredoxin. Sulfite reductase (acceptor) [EC 1.8.99.1] catalyzes the iron-dependent reaction of H2S with an acceptor and three water to produce sulfite and the reduced acceptor. A stoichiometry of six molecules of reduced methyl violo-gen per molecule of sulfide formed was reported. See also Desulfofuscidin Desulforubidin... 

In this review, although we have tried to cover the necessary background information on the function and structure of the AAHs, our main goal has been to offer information on the catalytic mechanism operating in these non-heme iron-dependent enzymes. In particular, we have focused on mechanistically relevant information that has emerged from molecular-level computational studies. Special attention is paid to our own work in this area, although we have tried to put our results in the context of other contributions in the field. 

Mukherjee M, Sievers SA, Brown MT, Johnson PJ (2006b) Identification and biochemical characterization of serine hydroxymethyl transferase in the hydrogenosome of Trichomonas vaginalis. Eukaryot Cell 5 2072-2078 Muller M (1993) The hydrogenosome. J Gen Microbiol 139 2879-2889 Nixon JE et al. (2003) Iron-dependent hydrogenases of Entamoeba histolytica and Giardia lamblia activity of the recombinant entamoebic enzyme and evidence for lateral gene transfer. Biol Bull 204 1-9... 

In this mechanism X+ represents an oxidant—a dangerously reactive peroxide perhaps, or even Fe(III) which must be reduced to Fe(TI) as part of the reaction cycle of many iron-dependent enzymes. 

The ability to synthesise ascorbic acid from glucose is absent in a small group of animal species that include man, primates, the guinea pig and the fruit-bat this is due to the absence of the gene that codes for one of the enzymes required for ascorbate synthesis. These species are therefore dependent on an external source of the vitamin in their diet and it is needed as a cofactor for several hydroxylase enzymes, notably the iron-dependent proline and lysine hydroxylases and the copper-dependent dopamine-(3-hydroxylase the function of ascorbate in these enzymes is likely to be its ability to keep the metal in the reduced form which is necessary for hydroxylation. The ability of ascorbate to reduce Fe3+ to Fe2+ is important in promoting the gastrointestinal uptake of iron and for its release from the iron store ferritin. 

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