SOD1+Gene

During aerobic cellular respiration, oxygen is used and becomes the final electron acceptor in the electron transport chain. This is a necessary product in order to generate ATP, although oxygen, in its excited state gives rise to harmful types such as superoxide radicals (O2-), hydroxyl radicals(•OH),and hydrogen peroxide(H2O2). These are known as reactive oxygen species or ROS. Accumulation of ROS has a variety of harmful effects on the body, most effect body tissues. ROS cause peroxidation of fatty acids, consequently affecting cell membrane lipids. Oxyradical attack also affects DNA molecules, co-factors of other enzymes, and amino acids particularly sulfur-containing methionine and cysteine. As much as oxygen is essential to the life of all multicellular organisms, it also provides some physiological complications in its metabolism, and this has become known as ‘oxidative stress’. Cells lacking SOD1 cannot efficiently breakdown superoxide, and although superoxide itself is not very toxic, it reacts rapidly with other molecules forming highly toxic radicals. The superoxide anion spontaneously breaks down into O2 and H2O2. However, superoxide reacts even faster with NOand can easily diffuse through membranes forming the toxic peroxynitrite, a powerful oxidant. Accumulation of this substance in cells particularly neurons results in nitric oxide-dependent neuron apoptosis (programmed cell death). This is thought to be one of the major causes of FALS and is strong evidence that may possibly hold a clue to how to fight this disease.

__The SOD1 gene contains__ -4 identical chains- each consisting of 153 residues -made up of 8 anti-parrallel Beta-pleaded sheets -5% alpha helices -7 loops

Chromosome 21

15 to 20% of cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the superoxide dismutase-1 gene on chromosome 21q22.1. Although most cases of SOD1-related familial ALS follow autosomal dominant inheritance, rare cases of autosomal recessive inheritance have been reported. These familial cases are the most important because they provide a link between a gene and a disease for which to work. The advantage to having a gene associated with a particular disease is shown where model organisms may be used to mimic the gene's expression and rather than testing on humans, using a species with a similar SOD1 gene expression. The most common case is that of Mus muscularis, the mouse, which is used in most ALS initial treatments. The reason being its mammalian heritage along with its genetic relatedness as shown below. A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. In the spectrum of ALS, most of he research done is with Mus muscularis, the mouse.We use the mouse as the model organism of choice because it contains the gene of interest along with the ability to be maintained in a laboratory environment.Although it shows below in the phylogenetic tree that Zebra fish, Denio Rerio, is more closely related to the Homo sapiens SOD1 gene. It is still must easier and cost efficient to breed mice, along with the fact that mice are one of the only mammals with the ability to breed so quickly.







Catalysis of the enzyme caused by the presence of copper. The copper ion undergoes a redox reaction below:



The SOD1 enzyme catalyses the metabolism of the harmful superoxide radical into hydrogen peroxide and oxygen. When the SOD1 gene does not function correctly, as is the case in familial linked ALS, the harmful reactive oxygen species disturb the SOD1 pathway and lead to neuronal cell strangulation and effectively kill the cell. When neurons are no longr able to trigger muscled they become unable to contract which leads to the atrophy. The muscles during the early stages of the disease twitch and have uncontrollable movements, especially in involuntary muscles of the face.

Amylotrophic Lateral Sclerosis