Oxidase Sulfate

Abstract

Three enzymes presently identified are active in animal, bacterial, and plant sulfur metabolism. They are believed to be mononuclear molybdenum proteins. These enzymes are sulfite oxidase (SO) present in mammals, plant sulfite oxidase, and bacterial sulfite dehydrogenase (SDH). The X-ray crystal structures of the enzymes reveal a molybdenum atom surrounded by closely identical pyramidal square coordination. The overall configurations of these proteins are distinct, however. In addition, the cofactors in these proteins vary from one another as well. The structural understanding of these proteins provides the basis for research into the role of individual amino acids in their catalysts. Sulfite oxidase in animals is involved in the last step of degradation of amino acids that contains sulfur. This enzyme is important in detoxifying excess sulfite. Deficiency of sulfur oxidase in human beings leads to a fatal genetic disorder that can cause early death. Impaired activity of sulfite oxidase is involved in neurotoxicity of sulfite. Sulfur oxidase from animals and sulfite dehydrogenase contains both heme and molybdenum domains unlike sulfur oxidase in plants which contains only molybdenum domain. Studies on intraprotein electron transfer from sulfite oxidase of animals and bacterial sulfite dehydrogenase show clear differences and similarities of two enzymes. There is a conformational change involved in the animal SO IET where interactions of electrostatics may control the connection of heme to molybdenum domain before the transfer of the electron. On the other hand, SDH interprotein electron transfer measurements show that IET occurs via protein medium which is different from that in sulfur oxidase of the animal.

Introduction

The only known transition metal from second-row transition metals with biological function across every form of life is molybdenum. There are more than fifty molybdoenzymes known to catalyse oxidation-reduction reactions that are vital in nitrogen, carbon and sulfur. Mononuclear molybdenum enzymes can be classified into three different groups which consist of DMSO reductase, xanthine oxidase, and sulfite oxidase families. Some of these enzymes including sulfur oxidase are of clinical importance for the health of human. The sulfite oxidase family consists of oxidising sulphite enzymes from animals and assimilatory nitrate reductases from plants. There are two classes of oxidising sulphite enzymes based on their electron transfer to molecular oxygen capability. These enzymes are;  Sulfite oxidase from animals and plants, EC 1.8.3.1 and sulfite dehydrogenase (SDH) in bacteria, EC 1.8.2.1. In this assessment, more information about the sulfite oxidase will be discussed in details.

Sulfite oxidase catalysed reactions

Sulphite oxidase is an enzyme that contains molybdenum cofactor and catalyses the oxidation of sulfite to sulfate in the final step of degradation of amino acids that contains sulfur.( Mehta et al.,2015)  Sulfite oxidase is found in the inter membrane space of the mitochondria. The sulfite oxidase exists as a homodimer in the intermembrane space. The figure below shows a mechanism reaction for sulfite oxidase. It is a schematic reaction of oxidation of-of sulfite to sulfate. A is the oxidised Mo centre. B is the Mo (IV) sulfate adducts that results from the sulfite attack on the equatorial group of oxo. C shows the free reduced Mo (IV) centre once the sulfate has been released.

Figure 1

Database used: PubMed

The sulphite oxidase catalytic cycle can be grouped into three stages: sulfite oxidation, electron transfer from the molybdenum to the iron to chromosome and electron transfer from metal to the chromosome c. The initial process is the joining of the sulfite and its oxidation to sulfate as shown in the figure above. Oxidation is achieved through joining the sulfite’s sulfur atom to the molybdenum through equatorial oxo-metal ligand and concomitant reduction of Mo (VI) to Mo (IV). (Hänsch, 2007).

During oxidation of sulfite to sulfate, the oxygen used comes from water. In a whole stable oxidised state of the enzymes, the site of catalytic is almost square pyramid in shape with dioxo-molybdenum at the middle and three equatorial ligands of sulfur and two oxo ligands, one axial and the other equatorial. The techniques for SOEs consist of sulfite attack on electrophilic ligand, which is solvent exposed. Sulfate hydrolysis follows and two orderly single electron to take back the enzyme to the completely oxidised stable state. Plant sulfite oxidase integrates its catalytic reaction with another non-enzymatic phase hydrogen peroxide from the reaction oxidises another sulfite molecule. In vitro plant, sulfite oxidase leads to two molecules oxidation in each catalytic cycle. Sulfite oxidase could be responsible for extracting sulfite as the metabolite that is toxic.  The catalysed reaction by various enzymes was applied by scientists who wanted explain the radicals-adenosylmethionine enzymes that take part in biosynthesis of molybdopterin, menaquinone, thiamine, coenzyme F420 and heme. ( Velayutham, Hemann, Cardounel, & Zweier, 2016). They were determined on significant rearrangements of complex organics, which mostly do not have precedent biological or organic chemistry. (Mehta, Abdelwahed. Mahanta, Fedoseyenko,, Philmus,, Cooper, and  Begley, 2015)

Physiological function of the sulfite oxidase

Molybdenum requires being a unique cofactor to complexed with for it to be catalytically active.  Molybdenum is joined to a pterin to make a cofactor Moco apart from Mo-nitrogenase of bacterial where the molybdenum is a part of FeMo-cofactor. (Johnson-Winters, Tollin, & Enemark, 2010).  In eukaryotes, the most famous Mo enzymes are xanthine dehydrogenase, sulphite oxidase, nitrate reductase, mitochondrial amidoxime reductase and aldehyde oxidase. Moco biosynthesis comprises of six-protein complex interaction, and it is a four steps process. This process also requires ATP, iron, and copper. After synthesis of moco, it is distributed to the Mo-enzymes apoproteins by moco binding proteins(carrier). (Johnson-Winters, Tollin, & Enemark, 2010). In mammals, sulfite oxidase is used during catalyzation of oxidation of sulfite to sulfate process with ferricytochrome c, final step of metabolism of amino acids that contains sulfur.

SO₃^-2 + H₂O + 2Fe (III) Cyt c              SO₄^-2 + 2Fe (II) Cyt c + 2H+

Sulfite oxidase also plays a vital role in degradation of exogenously supplied sulfur dioxide and sulfite. Urine of animals exposed to sulfur dioxide or disposed to parenteral bis-sulfite has been found to contain approximately 80 -90% of sulfate. Studies show that human gets rid of 1 gramme of SO42- per day.( Hänsch and Mendel, 2009)

SO₃ ²⁻ + O₂ + H₂O → SO₄ ²⁻ + H₂O₂

Sulfite oxidase from plants have a function of detoxifying sulfite.  Sulfite is a metabolite that is toxic and needs to be removed to prevent the plants from many sulfites obtained from SO2 gas in the atmosphere. It is believed that plants sulfite oxidase could serve as ‘’safety valve’’ for degrading excess sulfite and protect the cells from sulfite lysis. The equation below shows the conversion of atmospheric sulfur dioxide to sulfite. (Johnson-Winters, Nordstrom, Davis, Tollin, Enemark, 2010). 

SO2 + H2O → (SO2 ⋅ H2O) → HSO3 − + H + ↔ SO3 2− + 2H-

Plants oxidase is therefore vital to biosphere sulfur cycling and industrial pollution adaptation. Child lacking hepatic sulfate oxidase discovery stressed the importance of active sulfur oxidase in human being. In plants, sulfite oxidase is involved in sulfite degradation. Additionally is also used as the intermediate enzyme in sulfate assimilatory reduction 

of Mo (VI) to Mo (IV). (Hänsch, 2007).

During oxidation of sulfite to sulfate, the oxygen used comes from water. In a whole stable oxidised state of the enzymes, the site of catalytic is almost square pyramid in shape with dioxo-molybdenum at the middle and three equatorial ligands of sulfur and two oxo ligands, one axial and the other equatorial. The techniques for SOEs consist