Summary Schematics

This chapter represents a collection of pictorial representations of the six previous chapters. It attempts to bring into sharp focus what is known and what is not known about the redox systems that have been previously explored in depth. The purpose is to give position and direction for present and future research, respectively. Schematic 1 <target id="page_156" target-type="page">156</target>The green hemoprotein of red blood cells as a superoxide methemoglobin transferase in red blood cells and its comparison to methemoglobin (cytochrome b₅) reductase. Cytb₅Fp = methemoglobin (cytochrome b₅) reductase; Cytb₅ = soluble cytochrome b₅; GHP(Fe⁺² or Fe⁺³) = green hemoprotein, reduced or oxidized, respectively; MetHb = methemoglobin; Hb_d4 = deoxyhemoglobin; Hb₄(O₂)₄ = oxyhemoglobin. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page156_1.tif"/> Schematic 2 The green hemoprotein, or phosphoenolpyruvate carboxykinase ferroactivator (GHP(Fe⁺² _xS_x)), of hepatocytes. PEP = phosphoenolpyruvate; PEPCK_A or PEPCK_I = phosphoenolpyruvate carboxykinase, active or inactive forms, respectively; LDH, lactate dehydrogenase; ITP = inosine triphosphate; PAC = pyruvate carboxylase. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page156_2.tif"/> Schematic 3 <target id="page_157" target-type="page">157</target>NADPH oxidase in leukocytes. Part = particulate antigen; Lyso = lysozyme; Prot = protease; FC = Fc portion of immunoglobulin; MPO = myeloperoxidase; PKC = protein kinase C; PL = phagolysosome; ARF₁ and ARF₃ = degranulation co-factors; PLD = phospholipase D; F⁻ = fluoride ion, a metabolic stimulator; FMLP = <italic>N</italic>-formyl-<sc>l</sc>-methionyl-<sc>l</sc>-leucyl-<sc>l</sc>-phenylalanine, a chemotactic and oxidative-burst-stimulating peptide; <inline-formula> <alternatives> <mml:math display="inline"> <mml:msubsup> <mml:mtext>Ca</mml:mtext> <mml:mn>0</mml:mn> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>2</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> <inline-graphic xlink:href="<a href="https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/eq44.tif" target="_blank">https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/eq44.tif</a>"/> </alternatives> </inline-formula> or <inline-formula> <alternatives> <mml:math display="inline"> <mml:msubsup> <mml:mtext>Ca</mml:mtext> <mml:mn>1</mml:mn> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>2</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> <inline-graphic xlink:href="<a href="https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/eq45.tif" target="_blank">https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/eq45.tif</a>"/> </alternatives> </inline-formula>, extracellular and intracellular calcium ions, respectively; N = nucleus of cell; CM = cell membrane; RY = ryanodine receptor; IP₃ = inositol triphosphate; DAG = diacylglycerol; tRNA = transfer RNA; CADPR = cyclic adenosine diphosphate ribose; TK = tyrosine kinase; PLC = phospholipase C; gI = gamma-interferon; PS = protein synthesis; HMS = hexose monophosphate shunt; 47_p GAP = GTPase-activating component of NADPH oxidase; RaplA = GTP-binding protein (G-protein) of NADPH oxidase; Rac₂ GP = a G-protein component of NADPH oxidase; 67_p = a cytoplasmic component of NADPH oxidase of unknown function; Fp91 = the flavoprotein component of the membrane-bound cytochrome b₅₅₈ or b₂₄₅; Hp22 = the heme-binding component of cytochrome b₅₅₈; (+) or (-), positive or negative effects on the pathway, respectively. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page157_3.tif"/> Schematic 4 <target id="page_158" target-type="page">158</target>Nitric oxide synthase in neurons. E = glutamate; SGC = soluble guanylate cyclase; CGMP = cyclic guanosine monophosphate; NMDA = <italic>N</italic>-methyl-<sc>d</sc>-aspartate; CAL=calmodulin; NOSC = constitutive neuronal nitric oxide synthase; CIT = citrulline; L-ARG = <sc>l</sc>-arginine; O₂ = oxygen; P = protein; P_p = phosphorylated protein; CGMP CK? = unidentified cGMP-dependent protein kinases; N = nucleus of cell; G-G-P = glucose to glucose-6-phosphate conversion; HMS = hexose monophosphate shunt; MRNA = messenger RNA; [Ca⁺²]ⁱ = intracellular calcium ion concentration; NO˙ = nitric oxide. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page158_4.tif"/> Schematic 5 Nitric oxide synthase of hepatocytes (hepNOS). TNF = tumor necrosis factor; LPS = lipopolysaccharide, or endotoxin; gI = gamma-interferon; PLC = phospholipase C; TK = tyrosine kinase; DAG = diacylglycerol; PKC = protein kinase C; IP₃ = inositol triphosphate; PLXs = variety of phospholipases (unidentified); NOS_i = hepNOS, or inducible hepatocyte nitric oxide synthase; L-ARG = <sc>l</sc>-arginine; Cit = citrulline; Mit = mitochondria; SGC = soluble guanylate cyclase; Pp? = phosphorylated protein, unidentified; CGMP PK? = unidentified cyclic guanylate monophosphate-dependent protein kinase; (+) or (-), positive or negative effects on the pathway, respectively. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page158_5.tif"/> Schematic 6 <target id="page_159" target-type="page">159</target>Nitric oxide synthase in the macrophage being used to attack a target cell. M = macrophage; TC = target cell; TNF = tumor necrosis factor; LPS = lipopolysaccharide, or endotoxin; gI = gamma-interferon; TK = tyrosine kinase; PLC = phospholipase C; DAG = diacylglycerol; IP₃ = inositol triphosphate; rasp21 = a cytoplasmic G-protein; cd K = cyclin-dependent kinase involved in the cell cycle; NFKB = NF-kappa-B, a transcription factor; PKC = protein kinase C; NOS_i = macNOS, inducible macrophage nitric oxide synthase; HMS = hexose monophosphate shunt; <sc>l</sc>-Arg = <sc>l</sc>-arginine; Cit = citrulline; Mit = mitochondria; PS = protein synthesis; NO˙ = nitric oxide; ADPR-P = adenosine diphosphate ribosylated protein; MSF? = an unidentified macrophage stress factor; Prot = calcium ion-dependent protease; SGC = soluble guanylate cyclase; RV = retrovirus (latent, then expressed); ENDON = endonuclease, involved with apoptosis; B = bleb formation, associated with apoptosis. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page159_6.tif"/> Schematic 7 <target id="page_160" target-type="page">160</target>Extracellular disulfide reductase in hepatocytes. C = cysteine; E = glutamic acid; gGCS = gamma-glutamylcysteinyl synthase; Eg-C = gamma-glutamylcysteine; G = glycine; GSHS = glutathione synthase; GSH = reduced glutathione. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page160_7.tif"/> Schematic 8 Extracellular disulfide reductase in fibroblasts. DR = disulfide reductase; Gln = glutamine; Gln = glutamic acid; G = glycine; GSH = reduced glutathione; GSSG = oxidized glutathione; C_yS₂ = cystine; C_ySH = cysteine; <inline-formula> <alternatives> <mml:math display="inline"> <mml:msubsup> <mml:mtext>X</mml:mtext> <mml:mtext>C</mml:mtext> <mml:mo>−</mml:mo> </mml:msubsup> </mml:math> <inline-graphic xlink:href="<a href="https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/eq46.tif" target="_blank">https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/eq46.tif</a>"/> </alternatives> </inline-formula> and ASC = amino acid transporters. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page160_8.tif"/> Schematic 9 <target id="page_161" target-type="page">161</target>Extracellular disulfide reductase in macrophages (M) and lymphocytes (L). R = receptor, unidentified; AC = adenylate cyclase; cAMP = cyclic adenosine monophosphate; mRNA = messenger RNA; PS = protein synthesis; LPS = lipopolysaccharide, or endotoxin; TK = tyrosine kinase; PLC = phospholipase C; PLXs = other phospholipases; XO⁻ = hypohalous acids; R_a = radiation (ionizing and nonionizing); DAG = diacylglycerol; PKC = protein kinase C; AA = arachidonic acid; LO_x = lipoxygenase; GSH = reduced glutathione; LT_S = leukotrienes; LTC = leukotriene C; CO_x = cyclooxygenase; PG = prostaglandins; PGE₂ = prostaglandin E₂; HMS = hexose monophosphate shunt; GSSG = oxidized glutathione; C_ysSSC_ys or C_yS₂ = cystine; C_ysH = cysteine; b = cytochrome b component; EDR = extracellular disulfide reductase; L = unidentified ligand; IL^˙2 = interleukin 2; N = nucleus of cell; ASC = amino acid transporter. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page161_9.tif"/> Schematic 10 <target id="page_162" target-type="page">162</target>Assimilatory nitrate and nitrite reductase. CP = chloroplast; NR = nitrate reductase; Fp = flavoprotein of nitrate reductase or nitrite reductase; b = cytochrome b component of nitrate reductase; Mo = molybdenum component of nitrate reductase; NiR = nitrite reductase; H4 = tetraheme component of nitrite reductase; FeS = nonheme-iron-sulfur component of nitrite reductase; G = glutamine synthetase. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page162_10.tif"/> Schematic 11 <target id="page_163" target-type="page">163</target>Dissimilatory nitrate metabolism. NiRs = assimilatory nitrite reductase; AmA = amino acids; C₄ = tetracytochrome c component of periplasmic dissimilatory nitrate reductase; Cu = copper of periplasmic dissimilatory nitrate reductase or nitrous oxide reductase; C = cytochrome c components of dissimilatory nitrite reductase or nitric oxide reductase; b = cytochrome b components of nitrate or nitric oxide reductases; d₁ = d heme component of dissimilatory nitrite reductase; Mo = molybdenum-containing component of dissimilatory nitrate reductase; PPS = periplasmic space; Fp = flavoprotein component of nitrate reductase; Fp? = unidentified flavoprotein components of other nitrogen oxide reductases. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page163_11.tif"/> Schematic 12 <target id="page_165" target-type="page">165</target>DALM synthase. (A) Nitrosonium intermediate formation on dissimilatory aerobic membrane-bound bacterial nitrate reductase: M = bacterial membrane; H = heme of b cytochrome; FAD = flavin adenine dinucleotide; Mo = molybdenum-binding component; the arrows indicate the progression of the DALM-forming process. (B) The binding of luminol near the nitrosonium intermediate. (C) The diazotization of luminol and nucleophilic attack of the diazonium by the alpha amino group of 3-amino-<sc>l</sc>-tyrosine. (D) Repetitive diazotizations of the aromatic amines of 3-amino-<sc>l</sc>-tyrosines and displacement of the diazonium groups as nitrogen gas by the alpha amino groups of additional 3-amino-<sc>l</sc>-tyrosines to form the DALM polymer on the nitrate reductase. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page164_12A.tif"/> https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page164_12B.tif"/> https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page165_12C.tif"/> https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page165_12D.tif"/> Schematic 13 <target id="page_166" target-type="page">166</target>The hypothetical type-b cytochrome sensor/switch. b_s = the type-b cytochrome sensor; UV = ultraviolet light; Me⁺² or Me⁺³ = reduced and oxidized transition, or heavy-metal ions; I = ionizing radiation; BR = bilirubin; HO_x = heme oxygenase; CO = carbon monoxide; H_e = heme; PS = protein synthesis; Fer = ferritin; PLX = unidentified phospholipase; HSPAF = heat shock protein activating factor; HSP = heat shock protein; Apob = cytochrome b without a heme; NOH_e = nitric oxide bound to free heme; SGC = soluble guanylate cyclase; HPETE = hydroperoxyeicosatetranoic acids; PKC = protein kinase C; LO_x = lipoxygenase; G(+) = positive growth effects; TK = tyrosine kinase; ADPR-P = adenosine diphosphate ribosylated protein; (Poly)-ADPR = polyadenosine diphosphate ribose; AA = arachidonic acid; DNAr = DNA repair; BCL₂ = the gene product BCL₂ has a negative effect on the oxidative activity of the sensor; p52(+) = the gene product p53 has a positive effect on the sensor; SF = stress factor; SFR = stress factor receptor; RV = retrovirus such as HIV; N = cell nucleus. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781351077415/fddf8ef2-9870-44d0-940d-a2a44584cbe2/content/page165_13.tif"/> 164