User:AdamUsmani/Myeloperoxidase

EC Number
The EC number of myeloperoxidase (MPO) is 1.11.2.2. The first digit, 1, places the enzyme into a class the class which catalyzes oxidoreductase reactions. The second digit, 11, classifies the enzyme as a peroxidase. The final digits, 2 and 2 identify specifically myeloperoxidase.

Reaction Pathway
The major reaction myeloperoxidase catalyzes is the conversion of hydrogen peroxide and chloride ions into hypochlorous acid. To achieve this, myeloperoxidase uses hydrogen peroxide as an electron acceptor (for breakdown) and chloride ions as substrates. This all occurs within a neutrophil cell, which is important for innate immune function. The myeloperoxidase activity within the phagosome of the neutrophil is conducive to the breakdown of pathogens, as hypochlorous acid is an effective antimicrobial agent.

Organisms containing Myeloperoxidase
Myeloperoxidase is currently found in many different organisms including mammals, birds, fish, reptiles, and amphibians. Myeloperoxidase deficiency is a well-documented disease among humans resulting in impaired immune function.

Function
Myeloperoxidase's main functions are within the immune system, functioning to essentially destroy pathogens. The way this works is that they are released from granules within the neutrophil into the phagosome for breakdown of pathogens. It does this by, as described before, catalysis of hydrogen peroxide into hypochlorous acid. This hypochlorous acid, along with destruction of pathogens, can also initiate and regulate inflammatory response. Inflammatory response affects metabolic pathways when activating immune cells. In order to provide energy necessary for inflammatory response, glycolysis is upregulated to provide ATP for phagocytosis. Following phagocytosis, the immune cells repair and remodel tissues, which can be aided by oxidized products of myeloperoxidase function.

Crystal Structures
There are many variations of the myeloperoxidase 3D structure, however they all follow a specific pattern. The myeloperoxidase enzyme typically weighs within the 135-200 kDa range, depending on the varying heavy chains it can be bound to. The enzyme is a heterotetramer with two light chains (15 kDa) and two glycosylated heavy chains which cause variability in weight. These heavy chains are bound to a heme group complex with calcium ions, arranged as a homodimer of heterodimers. The light and heavy chain monomers are connected by a cystine bridge at Cys153.

Active Sites
The heme group containing a central iron atom functions as the active site for myeloperoxidase. This heme group is active in the oxidoreductase activity on hydrogen peroxide. This is also where substrate (Cl- ions) may bind. Amino acid residues participate in the transfer of electrons during the reaction catalyzed by myeloperoxidase.

Structure effect on Function
As described before, the structure of myeloperoxidase is integral to its function. The central heme group acts as the active site for chloride ions and hydrogen peroxide. This is also the site of electron transfer, which allows myeloperoxidase to convert the two into hypochlorous acid. This allows the main function of myeloperoxidase, breakdown of pathogens, to occur.