Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways which include: (1.) etherphospholipid biosynthesis; (2.) fatty acid beta-oxidation; (3.) bile acid synthesis; (4.) docosahexaenoic acid (DHA) synthesis; (5.) fatty acid alpha-oxidation; (6.) glyoxylate metabolism; (7.) amino acid degradation, and (8.) ROS/RNS metabolism. The importance of peroxisomes for human health and development is exemplified by the existence of a large number of inborn errors of peroxisome metabolism in which there is an impairment in one or more of the metabolic functions of peroxisomes. Although the clinical signs and symptoms of affected patients differ depending upon the enzyme which is deficient and the extent of the deficiency, the disorders involved are usually (very) severe diseases with neurological dysfunction and early death in many of them. With respect to the role of peroxisomes in metabolism it is clear that peroxisomes are dependent on the functional interplay with other subcellular organelles to sustain their role in metabolism. Indeed, whereas mitochondria can oxidize fatty acids all the way to CO2 and H2O, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal beta-oxidation need to be shuttled to mitochondria for full oxidation to CO2 and H2O. Furthermore, NADH is generated during beta-oxidation in peroxisomes and beta-oxidation can only continue if peroxisomes are equipped with a mechanism to reoxidize NADH back to NAD(+), which is now known to be mediated by specific NAD(H)-redox shuttles. In this paper we describe the current state of knowledge about the functional interplay between peroxisomes and other subcellular compartments notably the mitochondria and endoplasmic reticulum for each of the metabolic pathways in which peroxisomes are involved.
...
PMID:Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum. 2685 47

Nitric oxide (NO) induces apoptosis selectively in NADPH oxidase-1-expressing malignant cells through peroxynitrite formation after the interaction of NO with extracellular superoxide anions. Membrane-associated proton pumps ensure the protonation of peroxynitrite, followed by decomposition into NO2 and hydroxyl radicals that cause lipid peroxidation and thus trigger the mitochondrial pathway of apoptosis. Distant from the cell membrane, NO is oxidized by oxygen, whereas peroxynitrite preferentially reacts with CO2. These consumption reactions attenuate apoptosis-inducing NO/peroxynitrite signaling. There is mutual interference between NO/peroxynitrite and HOCl signaling, based on complex NO/H2O2 interactions. Tumor progression leads to resistance of tumor cells against NO/peroxynitrite-dependent signaling through expression of membrane-associated catalase that oxidizes NO and decomposes peroxynitrite. There is a fine-tuned balance between catalase-mediated oxidation of NO and NO-dependent inhibition of catalase. Increasing the NO concentration through enhancement of NOS activity or inhibition of NO dioxygenase causes local inhibition of catalase. Then the interaction between free peroxynitrite and H2O2 allows the generation of singlet oxygen, which inactivates additional catalase molecules, allowing for the generation of additional singlet oxygen. Alternatively, singlet oxygen may activate the FAS receptor and thus cause enhancement of NOX1 activity and NOS expression. This leads to an autoamplificatory enhancement of catalase inactivation, followed by intercellular ROS/RNS-mediated apoptosis-inducing signaling. In addition, the signaling molecules HOCl and peroxynitrite seem to trigger immunogenic cell death and thus might establish a beneficial cytotoxic T cell response.
 ...
PMID:Nitric Oxide's Contribution to Selective Apoptosis Induction in Malignant Cells through Multiple Reaction Steps. 2943 Oct 84