A Review of the Catalytic Mechanism of Human Manganese Superoxide Dismutase

Abstract

Superoxide dismutases (SODs) are necessary antioxidant enzymes that protect cells from reactive oxygen species (ROS). Decreased levels of SODs or mutations that affect their catalytic activity have serious phenotypic consequences. SODs perform their bio-protective role by converting superoxide into oxygen and hydrogen peroxide by cyclic oxidation and reduction reactions with the active site metal. Mutations of SODs can cause cancer of the lung, colon, and lymphatic system, as well as neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis. While SODs have proven to be of significant biological importance since their discovery in 1968, the mechanistic nature of their catalytic function remains elusive. Extensive investigations with a multitude of approaches have tried to unveil the catalytic workings of SODs, but experimental limitations have impeded direct observations of the mechanism. Here, we focus on human MnSOD, the most significant enzyme in protecting against ROS in the human body. Human MnSOD resides in the mitochondrial matrix, the location of up to 90% of cellular ROS generation. We review the current knowledge of the MnSOD enzymatic mechanism and ongoing studies into solving the remaining mysteries.

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

“…There are three isoforms of SOD in mammals, namely, cytosolic Cu, Zn-SOD, mitochondrial Mn-SOD, and extracellular SOD (EC-SOD; [15,93]). It is proven that additional synthesis of SOD under stress conditions is an adaptive mechanism to decrease ROS formation, prevent oxidative stress and maintain adaptive homeostasis [145]. However, if the stress is too high, SOD activity is usually decreased following apoptosis activation.…”

Changes in Oxidation-antioxidation Function on the Thymus of Chickens Infected with Reticuloendotheliosis Virus

“…Under normal conditions, SOD can catalyze the disproportionation of O 2 ____˙ in the body to produce both H 2 O and H 2 O 2 [14]. H 2 O 2 can break the structure and function of the membrane through the cell membrane, react with purines and pyrimidines, and result in nucleic acid damage [29].…”

“…Moreover, ROS and RNS represent an important component of the pathogen resistance mechanism and may act as intracellular and intercellular signaling molecules; however, excessively high levels may also lead to oxidative stress [14]. ROS mainly include superoxide anions, hydroxyl radicals, other oxygen radicals, and H 2 O 2 .…”

Formal model of Parkinson’s disease neurons unveils possible causality links in the pathophysiology of the disease

“…Nature Reference L-Type NA E, MH, MB (Duda et al, 2016;Faber et al, 2007) T-Type NA E, MB (Branch et al, 2014;Poetschke et al, 2015) NCX 5000 Ca 2+ sec -1 1:3 (Ca 2+ : Na + ) MH, MB (Bers, 2002;Carafoli et al, 2001) PMCA NA 1 ATP per turn MB (Carafoli et al, 2001) Na/K ATPase 50 to 75% of the cell's ATP during one potential spike 2:3 (K + : Na + ) MB, MH (Gadsby, 2009;Howarth et al, 2012) mCU 1.10 6 Ca 2+ sec -1 Activated at high local concentration (~10 µM) MBH (Foskett and Madesh, 2014;Raffaello et al, 2016;Tan and Colombini, 2007) MAM 1.10 6 Ca 2+ sec -1 Activated at high local concentration (~10 µM) MB (Carafoli et al, 2001) mNCLX 5000 Ca 2+ sec -1 MB (Carafoli et al, 2001) RyR ~ 100 Ca 2+ sec -1 in average E, MB, MH (Carafoli et al, 2001;Raffaello et al, 2016) SERCA 200 Ca 2+ sec -1 E, MHB (Siegel George J. et al, 2006;Xu et al, 2016) KREBS 10 7 ATP sec -1 cell -1 10 7 ATP sec -1 cell -1 E (Mookerjee et al, 2017;Zimmerman et al, 2011) ETC SOD 10 5 -10 9 M -1 sec -1 (according to the physiological conditions and the literature) BM (Azadmanesh and Borgstahl, 2018;Sheng et al, 2014) Fenton Reaction 50 mol -1 dm 3 s -1 V (Kremer, 2003) DMT1 NA YBM (Andrews and Schmidt, 2007;Hadzhieva et al, 2014) TfR NA FTN1 NA…”