BIOINORGANIC CHEMISTRY Asim K. DasChapter 1 Ww 12 13 14 15 16 WwW 18 + Bloclements, Biomolecules and Background Materials Essential and Trace Elements and Bioinorganic Chemistry. Periodic Survey of Essent ial and Trace Elements : Biological Importance and Relative At ‘bundance of the Elements. ‘The Cell and Distribution of the Elements in the Cell, Biomolecules : Background Materials : sugars; organic acids; amino acids, peptides and proteins; enzymes; purine and pyrimidine bases, nucleosides, nucleotides and nucleic acids; NAD", NADP+, FAD, FMN and quinones; lipids and phospholipids. Bicligands in Biocoordirfation Chemistry. Biological Fune: 's of Biometals (Summary), Chemistry of Physiological Butters. Probable Mecrianism of Carcinogenesis and Mutagenesis by Some Chemical Coniounds and Physical Agents like lonising Radiation Exercise Chapter 2 : Metal-Protein Interaction : Metalloenzymes : Role of Metal tons in Biological Functions 2.1 Metal-Protein Interaction : Metalloproteins and Metal-Protein Complexes 2.2 Metalloenzymes and Metal-Activated Enzymes, 23 The Role of Metal fons in Metal-Protein Systems : structural ynthesis of macrocyclic bioligands; blocking of Lewis acid catalysis in metalloenzymes; biological redox reactions; electron transport process. 2.4 The Role of Metal lons in Basic Biological Reactions, 2.5 Binding of Transition Metal Complexes with DNA as Nucleic Acid Structural Probes : different conformations of ONA, general features of DNA-metal complex interaction, enantioselective interaction. Exercise 0 1-33 34-58Chapter. Blochemistry of Some Important Blometals, Storage, a ‘Transport and Activity 59.5, $1 Blochemistty of Iron and Iron-Metabolism : diiferent Fe-containi Proteins and enzymes and structural features of different Fe-proteing; ribonucleotide reductase (RR) and methane eppoxygenase (MMO); transport and storage in higher animals and lower organisms. 3:2 Biochemistry of Copper and Copper-Metabilism ; different Cu. Containing proteins and enzymes and their structural features; transport and storage of copper; microbial mining of copper, 53 Similarities between Copper and Iron in Biological Proces: 3.4 Biochemistry of Zine : different 2n-containing enzymes; chemistry behind nature's selection of Zn(l) in enzymatic activity; binding Atos of Znil) in proteins - catalytic and stroctures sites, 35° Vanadium, Chromium, Manganese, Cobalt, Molybdenum, Tungsten and Nickel in Biology, 36 Transport and Storage of the Metals other than Iron, 3.7 Biochemistry of Calcium : iological roles of calcium; binding sites of Ca? in proteins; storage of calcium; calmodulin (Ca? ion Carrion) Ga?*in muscle contraction; Cain blood Clotting process, 38 Comparison of Biochemistry of Ca?+ and Mg?*; Selectivity of Caz over Mg? in Biochemical Processes, Exercise Chapier 4 ; Transport Across the Membrane fon Pump lonophore 96-117 41 Active and Passive ‘Transport Across the Membrane, 42 ton Transport, 43° Crown Ethers and Cryptands ‘44° Naturally Occurring lonophores ; Naturally Occurring Antibiotics ~ diferent types; mechanism of ion transport; valinomycin; Ronactin; gramicidin, 45° Models of Active Transport of Cations Across the Biological Membrane through the lonophores, 46 Sodium-Potassium Pump and Na*-K*-ATP-ase, 47 Active Transport of Na* and K+ ‘ons and Nerve Impulse : Na* -and K+-channels, 48 Calcium Pump and Ca*-ATP-age, 49° Cotransnt of Sugars and Amino, ‘Acids Driven by Na*-Flow. Exercise Chapter 5 ; Onygen Transport and Oxygen Uptake Proteins 118-154 2): thermodynamic and kinetic aspects of activation of dioxygen through metal ions, 0)5.2 Basic Requirements of Etfective Oxygen Cartiors, 5.3 Biological Oxygen Carriers. 5.4 Distribution of Oxygen Carrying Proteins in Biological System. 5.5 Hemoglobin (Hb) and Myoglobin (Mb) in Oxygen Transport Mechanism : structural features of Hb and Mb; function of Hb and Mb; characteristics of O,-binding interaction with Hb and Mb — cooperativity, Hill-plot, allosteric effect; effect of Ht, Clr, CO, and 2,3-ciphosphoglycerate (DPG); mechanism of homotropic and heterotropic allosteric ‘effect; protection of heme {rom its irreversible oxidation by O,; model systems; role of distal and proximal histidine; function of globin protein; nature of Hb-O, binding: Poisioning towards Hb and Mb. 5.6 The Role ot Hemoglobin in Acid-B: Balance and Carbon Dioxide 5.7 Hemarythrin (Hr) — An Oxygen Uptake Motalloprotein, 5.8 Hemocyanin (Hc) — An Oxygen Uptake Metalloprotein. 5.9 Synthetic Oxygen Carriers : Coliman's compound; Vaska's complex; cobalt(ll)-schiff base complexes; pertluorochemicals (PFCs), 5.10 Hazards with Dioxygen in Biological System. Exercise Chapter 6: Metal-containing Enzymes in Hydrolysis, Decarboxylation and Group Transfer Reactions : Lewis Acidity of the Metal lons 155-175 61 Peptide Hydrolysis and Peptidases, 62 Carboxypeptidase A (CPA) — Structure and Reactivity. 6.3 Thermolysin — Structure and Reactivity. 64 Leucine Aminopeptidase — Structure and Reactivity. 65 Model Complexes of Peptidase Reactivity. 6.6 Adenosine Deaminase (ADA) and Cytidine Deaminase (CDA) — Structure and Reactivity. 6.7 Arginase — Structure and Reactivity. 6.8 —_ Urease — Structure and Reactivity. 6.9 Alkaline Phosphatase — Structure and Reactivity. 6.10 Purple Acid Phosphatase (PAP) — Structure and Reactivity. 6.11 Insulin Structure and Reactivity. 6.12 Hexokinase in Phosphorylation of Glucose and Enzymatic Reactivity of Some other Representative Kinase Enzymos. am6.13 Carbonic Anhydrase (CA) — Structure and Reactivity, 6.14 DNA Polymerase — Structure and Reactivity. 818 — Carboxylaso and Docarboxylaso — Structure and Reactivity, Exercise Chapter 7 + Metal lons in Electron Transport Proteins and Redox Enzymes 176-235 7-1 Franck-Condon Principle and Designing of Electron Transport Agente in Biological System, 7.2 Won-Sulur Proteins : gonoral features; rubredoxin (Ad); ferredoxins (Fd) ~ 2F@-28, Rieske contros, 4F0-48, high potential iron proteins (HIP), 9Fe-48, 8Fe-8S; Fe-S model compounds; nonredox Fe-S Protein, 7.9 Blue Copper Proteins : electron transport proteins and oxidase Proteins — laccase, ceruloplasmin and ascorbic acid oxidase (AA), 74 Nonblue Copper Oxidase Proteins : galactose oxidase (GO) and ‘amine oxidase. 78 Cytochromes : structural features and classification; cytochrom: 7.8 Cytochrome c oxidase ~ Structure and Reactivity 7.7 Cytochrome P-450 ~ Structure and Reactivity, 7-8 Superoxide Dismutase (SOD) — Structure and Roactvity 79 Catalase and Peroxidase — Structure and Reactivity. 7.10 Comparison of the Mechanisms of Action of Catalase, Peroxidase and Cytochrome P-450. 7-41 Oxygenases and Hydroxylases ; dioxygenases and mono- oxygenase; catochol-1,2-dioxygenase (CTD) and protocatechuate. ‘-cesvomnpes (PCD); tyrosinase; methane monooxygenase (MMO). 7.12 Alcohol Dehydrogent + Liver Alcohol Dehydrogenase (LADH) 7-13, Molybdenum Containing Redox Enzymes : structural features and mechaniam of oxo-transfer activity; xanthine oxidase, suite end Oxidase; nitrate raductase; formate dehydrogenase (FDH); aldehyde oxid 7.14 Tungsten Containing Redox Enzymes — Some Representative Examples; Chemistry of Tungstoenzymes vs. Molybdoenzymes. 7.15 Some Important Organic Redox Couples. Exercise (iv)Enzyme Catalysed Hydrogen Production 236-275 8.1 Oxidative Phosphorylation and Respiratory Chain: eloctron carrors in toepiratory chain; respiratory chain and synthesis of ATP; Cnergetics of the process and detection of ATP gonarating sites: blocking of respiratory chain, 5.2 Nitrogen Fixation : thermodynamic and kinotic aspects; dintrogen Complexes and activation of dinitrogen, $3 Nitrogenase (Ny-a80) in Biologioal Niirogon (N,) Fixation : occurrence; composition of the enzyme; structural aspects; model dliforent types of substrates active towards nitrogenase; function Gifforent units in the activity of N,-a8e; possible reaction pathway of reduction of Np. Ablological Nitrogen Fixation through Complexation. Photosynthesis and Chlorophyll : reaction; light phase and dark Phase reactions; chlorophyll - structural fontures; role of Mg(ll); electron transport chain (Z-scheme); oxygen evolving complex (CEC); antenna chlorophyll and reaction centro. 86 Hydrogenase : biological significance; molecular propertios of dihydrogen; composition of hydrogonase enzyme; hydrogenase Calatysed H,-prodluction — a source of anergy. 87 Carbon Monoxide Dehydrogenase (CODH) and Acetyl CoA Synthase (ACS). Exercise Chapter 9 = Phosphate Group Transfer and Metabolic Energy 276-304 ot Phosphate Transter : A Source of Metabolic Energy — ‘thermodyamic and kinetic aspects. 9.2 Phosphatases : General Mechanistic Aspects of Phosphate Group Transfer and Hydrolysis — studies on model complaxes, 9.3 Mechanism of Hydrolysis of ATP and Phosphate Group Tran from ATP : ATP-ase and Kinase Enzymes. 9.4 — Role of Phosphate in Glucose Metabolism : Glycolysis; tate of Pyruvate; citric acid cycle; glycogen synthe: Exercise Sbapter 10 : Vitamin B,,, Vitamin B, and Coenzymes 305-323 10.1, Vitamin By, and Coonzymes : structural feature; names of differant forms; chemistry of cobalamin; biochemical functions of cobalamins; models of vitamin B,,; special characteriatics of B,, coenzyme )10.2 Metnaneagenic Bacteria Factor (F-430 M), 103 Vitamin B, and Coanzymes : in the activity of transamination, cxidative deamination, decarboxylation and racomisation ot aming Acids; amino oxidase; lysyl oxidase, Exercise Chapter 11: Biochemistry of Nonmetals 324.33, 11.1 Biochemistry of nonmetals. 11.2 Nonmatals in Structural Uses : Examples of Biominoralisation, 11-3 Biological Rolo of Some Traco Nonmetals - boron; silicon: sultur: ‘selenium: arsenic ; fluorine; chlorine; bromina: iodine. 11.4 Biological Importance of Nitric Oxide (NO) Exercise Chapter 12 ; Metals and Chelation in Medicine 337-409 ‘12.1 Dependence of Biological Growth on the Concentration af Essential and Toxic Matas. 122 Disease duo to Moial Deficiency and its Treatment : Fe-, Zn-, Cu, Mo- deticiancy and treatment, 129° Motal ton Toxicity : sources of toxicity; goneral aspacis of mechanism of toxicity: importance of biomathytation in metal lon toxicology: chemical speciation of some metais in environments, 124 Toxic Elects of Matals : Fe-toxieity; Custoxicity and Wilson's disease; As-toxicity, Hg-toxicity; Pbstoxlelty; Cd-toxicity; Al-toxicity: Ca-tonscity: toxicity of other motals: radionuclide toxicity: metnis no carcinogens. 12.5 Natural Detoxiliation of Metal lon induced Toxicity and Cleanup of Toxic Metals by Plants, 12.6 Requirad Thermodynamic and Pharmacokinetic Properties of Chelating Drugs in Metal lon Detoxification. 12.7 Soma Representative Chelating Drugs used in Metal ion Detoxification : —SH group containing drugs: polyaming- ‘carboxylates; dosterrioxaminss; aurinetricarboxylic acid otc, 12.8 Limitations of Chelation Therapy in Matal lon Detoxification, 12.98 Radioprotective Chelating Drugs and Therapautic Activities of Some Special Chelating Agents by Inhibiting the Metalloanzymes, 12.10 Matal-Metal Detoxification : Antagonism and Synergism among the Essential Trace Elements. Anitimicrobial Activities of Metal Chelates and Cheiating Ligands ; ionophore antibiotics; tatracyclines; oxines; bleomycin; ‘As-, Sb- and Hg-compounds, ete, (vi)wi ary wa 1248 12.16 207 128 1209 Metal Chelation and the Activity of the Multipurpose Drug, Aspen, Mercunais as Ovuretics Antartrtic Gold Drugs and Chrysotherapy. Ant-ieftammatory Effects of Zinc and Copper Compounds. re Sak in the Treatment of Sickle Cell Anemia. Lamm Therapy in Psychiatric Mind Disorder. 12.20 Anticancer Activity of Some Other Metal Complexes. 22 Radioisotopes in Medicines. 12.22 Bamuth Compounds in Medicines. 1223 Vanadium a Insulin Mimetic Agents in the Treatment of Diabetes. 1224 Mirscs of Superoxide Dismutase (SOD) Enzymes as Therapeutic Agents in the Treatment of Oxidative Stress. induced Diseases ~ Synzymes. 12.28 Chelation and Role of Metal Complexes in Conventional Orug Resistant Malaria 1228 Metais and Chelation in Medicine — Summary Exercise Bibography/References (consulted) & Acknowledgement (wi) 12 O-CryBioelements, Biomolecules and Background Materials 1,1 ESSENTIAL AND TRACE ELEMENTS AND BIOINORGANIC CHEMISTRY The presence of about 40 different elements has been established in living bodies. The eleven most abundant elements in biological systems are H, O, C, N, Na, K, Ca, Mg, P, S, and Cl Among these, the first four elements, |.e. H, O, C and N, constitute about 99% of the total ‘atoms of a living body. These elements are involved to produce the biomolecules like water, carbohydrate, protein and fat The next eight most abundant elements are Mo, Mn, Fe, Co, Cu, Zn, F and |, These eight elements are present at trace quantities. These elements are called ‘essential trace elements but the term trace Is not well defined, For example, Fe is present in few g Iwhile Mo is present in few mg in an adult healthy body, but both are called trace elements. In fact, in his group, except for F (ca. 2.6 g per 70 kg body weight in human being) Fe and Zn, all other lessential trace elements are present in mg scale in a living body. The next eight important ‘elements are Li, Si, V, Cr, Se, Br, Sn and W. These elements are required at ultratrace concentrations (|.¢. at the level of parts per ten thousand million). The biometals are classified as essential metals and beneficial metals. In the absence of tial metals, the living system cannot survive and it eventually dies. On the other hand, in the ince of beneficial metals, the life process gets hampered but it cannot lead to death Essential metals : Na, K, Mg, Ca, Mn, Fe, Co, Cu, Zn, Mo. Beneficial metals : Li, V, Cr, Ni, Sn, W. ‘The approximate metal contents in a healthy human body (ca. 70 kg body weight) are as follows Na (100 g), K (200 g), Mg (35 g), Ca (1500 g), V (15 mg), Cr (2 mg), Mn (15 mg), Fe (5-7 g), Co {1.5 mg), Ni(S mq), Cu (200-300 mg), Zn (2-3 g), Mo (10 mg), The amount indicated does not measure the importance of the metal. The decreasing abundance of the transition metals in living organisms is : Fe, 2n, Cu, Mo, Cr, V and Ni. The total metal content shown here accounts for only ca, 2% of the total body weight. Excluding the metals Na, K, Mg and Ga, other metals ‘collectively weigh just a few grams (ca. 10 g) in a healthy body of ca. 70 kg. But these metals are extremely essential for the survival of life process : At biological pH, all these biometals (except for Na, K, and Ca to ‘CONNOL exist as free fons, They should form insoluble hydroxides and phosphates. By bioligands. these biometals form soluble complexes00m ta, oro thr mn tr Ch ‘Sone "AL en som saan rate ad Fe ar ens te wee Sdots enum sh se sums of Oy me sno and he emergence ‘Seen, TieFeS00 sa Mo SOD ae se ty ese etl on, le (Sec Dna Ore sts CoZn S00 ey ae ant oes nota Sertpal cotore."Thn Cr2r 500 wa mth eer sept ee of Op 1.3 TE CHLL AND DISTRRUTION OF THE HEMENTS 1 THE CLL sey staunch cl nd oa ae iW ‘trea ramose nes more hour use! heer we ‘ela arto of posh i ser gon prone 9 mane Sten renee hae ey hs by 8 ees Fld Morley ‘Sines. Tey maa ges apo Ucar to seca ‘sr ag cnaraten el tre nares Se.Fier 141.: tana Sv mtd ns of Dd Fey eae 143 om ae eda a area nares a ee ne Sears ane Suse eee See Sao ‘Swecrmers cht el be ese Oh epeePe casting ety amin ay MACHINEDstn etna oie a | peel rerienctery (ee Maca cue cin ch are se og gaan Teele stasen an nou on we daca et Sl Pa 1 Sa ned Fer A oda eos ae i ‘epshep hr ae e ee wis ths pope a ‘Demet mie pono ihe mgs 10100 he Te at totam npn de toa eden ee Py ce ote teh a me te ee Sc smc fe tin Th pl rem sid pee salen toose ape tacrn pr daca eesaea Taso conn ae tom wach nein be ne ot aye meiner ees cea a a all [ete s tram cog tere bec ee4482 jonencarse creas een cnr et nar rn ne to a lading ecb eee) ceive nay ged rh te fama, of lie el dave Te SS nage ome! om Be eee (een bf See 113K era ere —414 jmodfocave onnemn ge 1438: Dagsmainpmeratonl pie sce Cceterery ttre of the protein Stn of man pes ae ty che fan coke fone The gumay ance lon fle et eats, Heelan comers tow teh my ec To eBtone pet wen ernie, Tec ‘Sesdejdensine sommes ih es power. 9 ued The bon graSie erteary strectore of DNA gues the seqsence af eoxsritoniciotes it Sie See ease ts me ee Aad tutes shout hr san snr be sod it ere Po vpn Foatng sr ony 1051) m te rane! one pepe chan he ‘rund ato DN sel ty Fog recon bnew Se DNA aes SES het ek eying atone Hedman mtactor LABS EE 1a30) eee ch fyrne AT od gure whore 6.) Tem ‘Shae neces eieen he company sn con secondary “The por grvps ie aes ce nd phorphaver baton me en sarong sqaure sow harpoon On ee ad, (elope ce Gees ead ttc hve sed om peta bth ydrphoncitretion and Mending seen fe dcton of tt ae nce of DNA, Teasend me 2515" Ty cnt el fate mosis $B Be4m jmonorcinse ewan none wim mtr pepe etn thin Latah eee eng cements ee cern heeirmaeaa Tae iia reer tens one eset a8 i ee MN ie Bon Prt ats pen mena san nF 1458 ] a i k i e148: Stent opm of pees rile one pn eget {relent ete cde ONA sa Lee be roaeg DA tan ap at AA 27% fab Patty — Neon Cavers in the etna BAD cad ik ee iee ne nel otc mrcces ore Solrroienamen coca Be Aovinss toy on” Moin) Shee 1484: foe, res ere gine, tien eos nell open Ta sand sb ond corse Te ame dat oc hk Ieprettl The naa ire res seo pce The oa {arm minal syn ota tu pron mtr ded es Ge "ett sous ma rad he my by ben nino ‘seg 6/Fa 8.11 tah send phone betgurons Beerga tis ing wth ad Te soos ou eat mieSerene ra eo Agni meine, sa cn cargo mle ta Sth meteg te oaose pee, MGC ATPase the res potene herman cams Sosa A Me eg site, ATP cn. toga reuptake. Rein a ne tance fcr CT) eo mea: ee oe ocala ced ran yo GATf Pa Sree a ays. Tare BEIT be ne teen Sacer ns repr et on C/O FOYT Sa cpt ceteris SY Rae eeee cs apie nr wr Se cps ee ot tn nr Te SEIT cerns os GEES tegen ee i mr yd HCO, th he ES ae Ta odo “ea ge 3 eine te ton rr FCO Siete ope om Siberia e960 (6a He hon 7 Hepa raonis a HOO, + erst “Manne 9 = 74 eof COSCO, wc rm ~ 7st toby St enn $400; 11C0 20 C0, peat fom, Inthe whee on Hons rm he ong acon orb N00; = oe oO, 400, == 40 +0, eae, (Chea Hise chlo Ht al cnet of one no ages SS mt, ay a ey es thnaininaterseice ‘Wedges soon se. The “Oe rc! ts Hato 0 pode heh urn reco wih he mar oxen to profs the poral ad ‘ipsa Tose pecomsted an oor soe se. The mck by “OH, (SLES chen iar arminton at fe C8 come ef panne andar ‘incorporation Be cote eee‘Metal-Protein Interaction : Metalloenzy! Role of Metal lons in Biological Functions 12.) METAL-PROTEIN INTERACTION : METALLOPROTEINS ‘AND METAL PROTEIN COMPLEXES mere cn of en ve tre om alton nh Tha, pentane es an 4 31) ocarna nay pro ey pro he Peereeti eat extol (C0. ane (NP), ro (OF, lS, Bez gta te Thee hnctoel ip canparpate competion with te met ‘Bed onthe sent fran tern, he me cen ae on Ds ne Sa elec cng mtalloeny wd metloctoted Prot ere combece Inaiy meactted errs) Ba tere 670 sharp Fert re regex nos of he eum onset the metal ro iteracon ty are auricles + apoprcten =" talon en 1 vey ie, the teraction leno mtllopsen and K reat sa leno metalctated pon DMalloprotctns Here the rt oe 50 Bln ith te poten ta te et can ened eran ner part ofthe protein srctre tc css, he tion ca pest creme chem arch. The tans ery mach pectic ch ‘The acaty ofthe mop tf be cncrd etl remove Metabacthated Precis: ich cos, tert en reves combined wt he ‘ed hepealinncan hema ine dsr of te met, he poten ec | Gite oqin echucl yt wean che mol on. Srctnes, herve metal on ‘sed ter retaliate ct Ths, bo i eter 1 (Goriraonenirnin! oft oe on sedate met on Bolg fects, Compottion ofthe metal protein ster: For mallprotins ard metallensymes tata lcs roti cso ata 2 costa sal stb puyol he seen scene finaly acer tw contat vl wher the stm no pure sate Ths rato ges tlt alma ten inthe mace The mol mao of meta to proton oe of protein conta one leo 20 an ae aonss vo So co fs Ca NO) a al on cnar ssc te meal er ely ds al Spearhead seme pant Sern nmo a Scere on The ponte gare and serves be hy the gener tem cfr ‘melas, coca te See mean get 80 ener Aa forte cyte ease The soe oy opengl er ins —H) Mrdrleen wich case he byte cue. Toes peony, ‘Serpe, wees tg othe way |) Oxidoreductases sneha don acon, Sobers nd omeree hs) arangenen ef Cent ath cathe cage of C-0, C-N, CC bo of eer te ror dle bts Thy cana ca te etn co ose banal hy cance te wats cng he nono cso sh‘eae dO, (SreeSS —<$<$~__——— parr ieinyAered cect er a foc se a en mica trading with ve DNA bases destabilses Sa gotten an te retention cra ies eee fe Ss a Be meth ea ct Sa te ec cna Sees ie an, ere merase Soest gatas ere ty eee a ee wa fee ae Teun alors beso forged." ncn ners a create aes (TC allay Tike’ noe, Now enact eh nt de ‘ina Dh nam rime prnt at pt polo hrc stitch On ans tn one ‘rte Gacy and hen © can nein and ka os sn NO ce seen nace Re aaa ees oe cen este sent oles ma tiny Bot hw mea or rb al cd chet amroil er ssl rH, re in etl ee ene tanta a det men cmp ce See ce em ry SeScheme 235.1 Mh on et the pct cen AO Pat Se 1481) hcg rex econ ay vee dif poi esl eon ar Inte on trae sie fo 2 tal earo rane fa 2 re ‘Merrion of nae sm. on ron “The pct tot tl let rao moa ‘mnie 2.3.6 Matl tons in econ Transport Process The pret etapa eorng bs pore kee rote" ‘eel FS pry Fete" couse ad ecamene Fe™ Re cat Te ‘SeedinChaper ‘24 THE ROLE OF METAL IONS IN THE BASIC OLOGICAL REACTIONS. ‘The ct impart tne eal acon Satna ton, loge ‘ao, and ome mele eer Protos Sc 8.5) ti ce, sl ee cone no chal ew beforeenue let olen he hen jroo PASO on one o ok tegeet fuason pny an. inporare cs ZAP ate corer of Bacher = [ATP in phesphorjton proces hen ao —— een aii ‘nt bsp 1 tapi compete 960" oe ‘Beslan pbs prs 32 1 be pa ‘lore aon 630 aH agin ma nap atthe charmer af AB ZONA we compa Te 38 ante 204 Chctriilewes af Rand ONAL FQ 25:11) =F a coy = ory permed [Ragtime | thw 8 Seeren pees | (i) Talia Tetons) 2 ” * 0 Yaesinew “som bet | 2p 1 trp tp pe sum Sein ‘mete ‘renee 04| se re)eer oben eau! how th sat tae eg th enc ol to ae st Th noes ey gut genes nd meted pes ‘aeee reece, pny ot tl i a ach ah hl ‘ennai pra Rapala we ay rly of he mica Fer gow Sung ot Rr comps St miner sme ba wan = croissant ‘Selmer spon Tor pow big f Rape tuple mah we rc See acc vacsar oak Se mht cl ome ee egw "ine geo ol sac, te Sg of omer ne nd we0 Prt of haphdnertags :Cmdrtn ty mil ee oh er ‘Borohaebodkon an onset tps opted ke BNA (u) Damage to Watson- sn Sep! snr ny ico compre on ae wt en Doman sane comin Cenc wa asthe a ecg Zhong enh a etn 18 2 158 thaubrenns wan sled se be eed beng may ‘els fn recente, fe bray onto we aed, Now {She mbar of Dap eyo he ben aii hc Blog aoles selection of Zn in hi nce acd ding preein uie une erm redox sty which cout damage the DNA inthe en re LT heer maa re ol te! te DNA Rae erin lel ste ‘Sel 2h pend DNA and RNA pm ar nw eid wd (ee crane pea cae ae OUR (Scurbce gene ernion a th ela en Mile ety depron Zeca ‘Stel fst The beth wet ard a cans we ao und tcp len (Sonn ner pement mothers er Sn of 2 Tis are aera rs ‘ppunt bctt tngrowth car Sare psf chcpens beni dew te (Siew cf 2 xh carson of 21, 7H0 an pre ‘erin Zr-dfceny qte common UK ater atin a eto owing cae = {0 Use of phosphate err cert Zo echt 2oJPO4, wich ene Zale ey Sata the rola veel 9 Decreased orp cnr i teal a aces ‘onal rg ching agent an she | RISES oe frp epee On ere ct ‘derenadia 20 compas wth 10205 or