The Structural Biochemistry of the Superoxide Dismutases
The discovery of superoxide dismutases (SODs), which convert superoxide radicals to molecular oxygen and hydrogen peroxide, has been termed the most important discovery of modern biology never to win a Nobel Prize.
Extracellular superoxide dismutase in biology and medicine
Accumulated evidence has shown that reactive oxygen species (ROS) are important mediators of cell signaling events such as inflammatory reactions (superoxide) and the maintenance of vascular tone (nitric oxide). Extracellular-SOD is found in the extracellular matrix of tissues and is ideally situated to prevent cell and tissue damage initiated by extracellularly produced ROS.
The role of copper, molybdenum, selenium, and zinc in nutrition and health
Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals. Copper, zinc, and selenium are involved in destruction of free radicals through cascading enzyme systems. Superoxide radicals are reduced to hydrogen peroxide by superoxide dismutases in the presence of copper and zinc cofactors. Hydrogen peroxide is then reduced to water by the selenium-glutathione peroxidase couple. Efficient removal of these superoxide free radicals maintains the integrity of membranes, reduces the risk of cancer, and slows the aging process.
Superoxide Dismutase Boosting the Body’s Primary Antioxidant Defense
Primary antioxidants such as superoxide dismutase are our first and most important line of defense against highly reactive, potentially destructive oxygen-derived free radicals. Researchers believe that SOD decreases with aging, and evidence suggests that boosting falling SOD levels may help guard against disease and extend life span.
Superoxide Dismutase (SOD) And Its Role In Maintaining Glutathione
SOD1 or CuZnSOD – intracellular SOD, requires copper (Cu) and zinc (Zn) to perform its function and protects the cell’s cytoplasm, the substances enclosed by the cell’s membrane where most of the cellular activity occurs.
Genetics Reference SOD1 Gene
The SOD1 gene provides instructions for making an enzyme called superoxide dismutase, which is abundant in cells throughout the body. This enzyme attaches (binds) to molecules of copper and zinc to break down toxic, charged oxygen molecules called superoxide radicals. Superoxide radicals can damage cells if too many accumulate within cells. Superoxide radicals are byproducts of normal cell processes, particularly energy-producing reactions, and must be broken down regularly.
Pharmacokinetics of PC-SOD, a lecithinized recombinant superoxide dismutase
Pharmacokinetics of PC-SOD, a lecithinized recombinant superoxide dismutase, after single- and multiple-dose administration to healthy Japanese and Caucasian To study the pharmacokinetics of single increasing intravenous doses (40-160 mg) and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC-SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-dose, open-label, dose-escalation part and a multiple-dose, single-blind, placebo-controlled part. The pharmacokinetics of PC-SOD were determined using noncompartmental and compartmental methods. Pharmacokinetic data from a study with PC-SOD in Caucasians were reanalyzed using the same methodology. The mean (SD) terminal half-life of PC-SOD in Japanese subjects was 25 (4) hours for the 40-mg and 80-mg doses and 31 (15) hours for the 160-mg dose. There was nonlinearity between dose-normalized C(max) and clearance (P values .002 and .022). After multiple dosing, steady state was reached after 5 days. The observed accumulation ratio was 2.6 (0.5). The pharmacokinetics of the single 80-mg dose were similar for Japanese and Caucasians. The pharmacokinetics of PC-SOD was shown to be nonlinear with dose, which may be attributable to a saturable clearing mechanism. The relatively long half-life of PC-SOD (>24 hours) suggests that it is worthwhile to study the compound as a protective agent in clinical conditions with free radical overload.
Human pharmacokinetics of intravenous recombinant human Cu/Zn superoxide dismutase
Oxidative stress plays an important role in human disease, but antioxidant therapies are limited. Under physiological conditions superoxide is controlled by the enzyme superoxide dismutase. A recombinant human Cu/Zn superoxide dismutase (rhSOD) might open new therapeutic possibilities. Our results show a good safety profile and predictable pharmacokinetics of rhSOD, suggesting that therapeutic exploratory studies might be safely conducted in humans.
Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance
The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals.