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Heme Oxygenase-1 in Kidney Health and Disease
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Pu Duann, Elias A. Lianos, Pei-Hui Lin
Heme is an iron-containing porphyrin complex and constitutes the prosthetic group of several hemoproteins with important biological functions. Heme is synthesized in the mitochondria with protoporphyrins supplied from its precursor succinyl-CoA from mitochondria TCA (Kreb) cycle, which then subsequently exported out via the mitochondrial transporter ATP-binding cassette (ABC) B10 after biosynthesis (7). Hemes are most commonly recognized as components of hemoglobin from red blood cells (erythrocytes). Some other examples of hemoproteins include myoglobin (enriched in muscle), catalases, heme peroxidase, cytochromes, and endothelial nitric oxide synthase (eNOS) (8). The redox-active nature of iron makes heme critically involved in modulation of oxidating-reducing activities of hemoproteins which engaged in oxygen transport (hemoglobin) and storage (myoglobin), mitochondrial electron transfer and energy transformation (cytochromes), hydrogen peroxide activation (heme peroxidase) or inactivation (catalases) and nitro oxide synthesis (eNOS) (9). In physiology, significant level of heme could arise from the destruction of aged red blood cells. Because heme also catalyzes the formation of toxic reactive oxygen species (ROS) and free hydroxyl radicals to induce pro-oxidant and cytotoxic effects, level of “free-heme” must be tightly regulated. Disturbed heme metabolism causes mitochondrial decay, oxidative stress, and iron accumulation has been linked to age-related diseases (10).
3-Nitrotyrosine: a versatile oxidative stress biomarker for major neurodegenerative diseases
Published in International Journal of Neuroscience, 2020
Maria Bandookwala, Pinaki Sengupta
However, NO metabolism is not a single pathway by which 3-NT is formed. Alternate pathways through heme peroxidase and myeloperoxidase (MPO) also juggernaut terminating into 3-NT. In the heme peroxidase pathway, endogenous peroxide converts NO2– to NO2via the highly oxidizing porphyrin ring radical (PRR•) thus mediating Tyr-nitration (reactions 9 and 10) [101].
COVID-19: captures iron and generates reactive oxygen species to damage the human immune system
Published in Autoimmunity, 2021
Haem peroxidase, a haem-containing enzyme, can use hydrogen peroxide as an electron acceptor to catalyse multiple oxidation reactions. Haem peroxidase includes two superfamilies: one is found in bacteria, fungi and plants, and the other is found in animals. Among them, Lignin fungi peroxidase has a strong capacity of ·OH generation [81]. In this study, we only selected conserved domains in fungal peroxidase.
Enzymatic cross-linking of collagens in organ fibrosis – resolution and assessment
Published in Expert Review of Molecular Diagnostics, 2021
Martin Pehrsson, Joachim Høg Mortensen, Tina Manon-Jensen, Anne-Christine Bay-Jensen, Morten Asser Karsdal, Michael Jonathan Davies
Similar to the fibrillar collagens, the tertiary structure of type IV collagen within the BM is stabilized by the formation of disulfide bridges [42] and LOX(L) mediated cross-links [11,104]. In contrast to fibrillary collagens, it is also stabilized by cross-links between the sidechains of methionine (Met)93 and Lys/Hyl211. The resulting sulfilimine cross-links occur as both intra- and inter-molecular species within the NC1 domain, and are of critical importance in the self-assembly of the protomer, and stabilization of the hexamers, within the BM [105]. PXDN is a member of the heme peroxidase super family of proteins, which includes myeloperoxidase, lactoperoxidase, eosinophil peroxidase, and thyroid peroxidase among others [106,107]. Unlike other peroxidases, PXDN appears to be uniquely involved in ECM assembly and type IV collagen cross-linking. Generation of the sulfilimine cross-links occurs as the trimeric PXDN complex associates with type IV collagen through its Ig C2 domain [108] thereby bringing its peroxidase domain into the proximity of Met93 and Lys/Hyl211. In the presence of bromide (Br−) and hydrogen peroxide (H2O2), PXDN generates the reactive intermediate hypobromous acid (HOBr) which oxidizes Met93 resulting in a halosulfonium ion intermediate. Subsequently this reacts with Lys/Hyl211 of an opposing protomer forming the sulfilimine bond [109–112]. The source of H2O2 for PXDN activity is unknown and may involve other enzymes [112,113]. The complexity of this process may help prevent unintended (artifactual) oxidation of other ECM components by the highly reactive intermediate HOBr [114–116] as has been reported recently. Being one of the more recently discovered cross-linking enzymes, the exact involvement of the basement membrane proteins surrounding type IV collagen in PXDN mediated cross-linking has yet to be fully elucidated, however the ECM characteristic domains of PXDN such as the leucine-rich repeats suggest interactions with laminin aiding the cross-linking of type IV collagen [108,117,118]. The enzymatic actions of TG2 and PXDN in the formation of collagen cross-links are presented in Figure 3.