Oxygen and nitrogen reactive species metabolism in peroxisomes. A, Principal peroxisomal metabolic pathways associated with peroxisomal ROS and NO production. ROS are produced in metabolic pathways such as β-oxidation, photorespiration, ureides metabolism, and polyamine oxidation, and in a small electron transport chain associated with the membrane (peroxisomal membrane proteins, PMP18 and PMP29; Figure 2B). NO is produced in peroxisomes by NOS-like (NOS-l) activity, although other sources, such as XOR, polyamine oxidation, and IBA metabolism, could also be involved. ROS, NO, and other RNS may leak out of the peroxisome (dashed arrows) and act as signal molecules that regulate cell metabolism and gene expression. B, Scheme of peroxisomal antioxidant defenses, RNS scavengers, and NAD(P)H supply. O₂^.− is regulated by SODs, while H₂O₂ is controlled by CAT, the ASC-GSH cycle, and GPx. Peroxynitrite (ONOO⁻) and GSNO are produced in peroxisomes by reaction of NO with O₂^.− and glutathione (GSH), respectively. GSNO can negatively regulate MDHAR and CAT through S-nitrosylation and nitration, and SOD may be regulated by nitration. SOD may indirectly control ONOO⁻ by regulating O₂^.− levels. Uric acid acts as an ONOO⁻ scavenger. NAD(P)H is supplied by the oxidative pentose phosphate pathway (G6PD; 6PGD), ICDH, MDH, and NUDIX19. 6PGD, 6 phosphogluconate dehydrogenase; AAT, amino acid translocator; AOC, allene oxide cyclase; AOS, allene oxide synthase; APX, ascorbate peroxidase; BADH, betaine aldehyde dehydrogenase; CAT, catalase; CuAO, copper amine oxidase1; DHAR, dehydroascorbate peroxidase; GOX1,2, glycolate oxidase1,2; G6PD, glucose-6-phosphate dehydrogenase; GGT, glutamate–glyoxylate aminotransferase; GlyT, glycerate–glycolate translocator; GR, glutathione reductase; GPx, glutathione peroxidase; H-Acyl-CoA, 3-hydroxyacyl-CoA; HPR, hydroxypyruvate reductase; IAA, indole-3-acetic acid; IBA, indole-3-butyric acid; IBR3, acyl-coA dehydrogenase/oxidase-like IBR3; ICDH, isocitrate dehydrogenase; KAT, L-3-ketoacyl-CoA-thiolase; LOX, lipoxygenase; MDH2, malate dehydrogenase; MDHAR, monodehydroascorbate peroxidase; MFP, multifunctional protein; OPCL1, OPC-8:0 CoA ligase1; NOS-l, NO synthase-like; NUDIX19, nudix hydrolase homolog 19; OPR3, OPDA reductase3; PAO3, polyamine oxidase3; PAO3/4, polyamine oxidase 3/4; PNC, peroxisomal ATP carrier; PXA1, peroxisomal ABC-transporter1; PXN, peroxisomal NAD carrier; SGT, serin–glyoxylate aminotransferase; UOX, urate oxidase.