Sulfide has the highest affinity to either the pulsed or partially reduced states of the enzyme, and is capable of partially reducing the enzyme at the heme a3 center. It is unclear whether endogenous H2S levels are sufficient to inhibit the enzyme. There is no interaction between hydrogen sulfide and the fully reduced conformation of COX.Methanol in methylated spirits is converted into formic acid, which also inhibits the same oxidase system. High levels of ATP can allosterically inhibit cytochrome c oxidase, binding from within the mitochondrial matrix. Extramitochondrial and subcellular localizations
Cytochrome c oxidase has 3 subunits which are encoded by mitochondrial DNA (cytochrome c oxidase subunit I, subunit II, and subunit III). Of these 3 subunits encoded by mitochondrial DNA, two have been identified in extramitochondrial locations. In pancreatic acinar tissue, these subunits were found in zymogen granules. Additionally, in the anterior pituitary, relatively high amounts of these subunits were found in growth hormone secretory granules. The extramitochondrial function of these cytochrome c oxidase subunits has not yet been characterized. Besides cytochrome c oxidase subunits, extramitochondrial localization has also been observed for large numbers of other mitochondrial proteins. This raises the possibility about existence of yet unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations. Genetic defects and disorders
Defects involving genetic mutations altering cytochrome c oxidase (COX) functionality or structure can result in severe, often fatal metabolic disorders. Such disorders usually manifest in early childhood and affect predominantly tissues with high energy demands (brain, heart, muscle).
Mutation in this gene causing disorder of phototransduction pathway through brain which detect light fail to function. Diagnosis
Paediatric nurses, medical officers and paediatricians trained in eye screening could detect small or large eyeballs, nystagmus, strabismus, “white pupils” and birth defects like coloboma and aniridia. For pregnant women from family with history of congenital blindness will be closely monitor and need to carry out genetic test in order to identify is there mutation occur or not. Gene therapy treatment
Gene therapy treatment is done as an outpatient. Patients come to the hospital for the treatment, then return home. Patients do not need to be monitored strictly or stay in the hospital. The gene therapy treatment is in vivo which involves the use of a delivery vector to transmit the therapeutic gene into the targeted cells. The delivery vector uses a recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2). The procedure is a single injection of the AAV2-hRPE65v2 therapeutic gene into the unilateral subretinal of the eye. Gene therapy can only improve eye vision, but cannot cure the condition. The therapeutic gene, Voretigene neparvovec (Luxturna), was the first gene therapy approved by FDA for inherited diseases. == References ==