Okay Visible audible Okay Ah sakit na ng lalamunan ko Wala kasing sumasagot eh Okay Um saan na tayo Dito Sige Review review of related literature Charot So what are Ross What is Ross Very simple What is Ross Miss Mendoza Sir sila po yung highly reactive molecules contain ox Okay So there are highly reactive molecules that contain oxygen So from the name itself Okay So Ross exist in different forms So what are those two forms DK Hello po rinig po ako yes okay yung yung rose po nag-exist siya sa different forms which is yung free radicals and nonradicals oxid po Okay What's the difference Okay yung free radicals po ito po iyung mga molecules na unpaired electrons So it makes them highly reactive Well yung um nonradicals oxidant po yung mga molecules na to um can easily generate po ng um radicals or can generate inredux reactions po or yung mga um since yung kanina na um unpaired ito po ay mga anong tawag doon Doesn't have an unpaired electron Okay sige thank you thank you DK So bakit ba reactive si Ross Bakit ba highly reactive si Ross W naman kung meron siyang ano ano bang bakit ba Lalala na si Free Radicals Miss Limpin Audible po sir Yep Yun yung mga free radicals po natin reactive po sila kasi yung meron po silang unpared electrons doun sa outer shell So it makes them desperately sick for another electron po para mag-achieve ng stability And then in the case po ng mga non-radical oxidants um kahit hindi po sila makapag-participate sa redox reactions um nagpo-produce pa rin po sila nitong mga free radicals na' and hence yun po yung nagco-cause po nung other damages pa po Okay sige thank you Okay So ano namang relationship or like um ano ang importance ni Rose or reactive oxygen species sa ano sa fiesta agad eh Sige Mr Rosario Sarad Payo Hello po sir So ah yung nag lecture po tayo nagbanggit po kayo ng tatlong ano po relevance niya Una po yung ano po kasi yung mga cells po naturally produce ay they naturally produce small amount po nung rose So since yung body po natin merong antioxidant ah defense mechanisms to keep them in check po Tapos however po when ionizing radiation po interacts dooon sa mga biological tissues natin it dramatically increases po iyung ross levels nga po which nabanggit nga po kanina yung mga molecular species po na possible may unfaired or ah walang unfaired pero highly reactive po Then yung second ah another thing pala po is around 70 to 80% po ng body is water po Ta's yyung mga ionizing radion po they mainly interact po doon sa water molecules na nagge-generate ng ROS through a process called radialysis Then yung Rose na po ito ito po yung umaatak sa mga biological ah ano natin at biological molecules such as yung DNA protein lipids po na pwedeng mag-cause ng cell and death However po nabanggit niyo rin po na double edged sword nga po siya kasi po pwede rin po siyang magamit sa radiotherapy kahit na nakaka nag-i-induce po siya ng different ah like different damages sa body natin Tapos yung pag-understand po sa reactive oxygen species essential po siya kasi pwede po natin siyang ma-apply like for example po sa radio protectors and yung mga radio sensitizers po na to Okay Very good Nire-record niyo ako no Sige Thank you Mr Del Rosario Very good Okay So yun yung importance ni or kung bakit natin inaaral si Rose or yung um importance niya or yung relevance niya sa radition biology Okay Sige Ano pa bang tatanong ko Okay What are oxidants What is oxidation What is reduction What is reducing agent Reducing agent Everything Go Miss Degana Ano sir Kapag po oxidation ang nangyayari dito is kapag yung isang molecule naglo-loose siya ng electron tapos yung molecule na nagco-cause ng oxidation process are called oxidizing agents or oxidants wherein sila yyung nagsi-steal ng electrons from a molecule Tapos yung reduction naman po nangyayari naman to kapag yung molecule nagge-gain siya ng electron Tapos ah yung molecule naman na nagco-cause ng reduction process are called uh reducing agent Where yung mga reducing agent na to sila naman yung nagdo-donate ng electrons sa other molecules T's in relation po sa hydrogen kapag oxidation it means losing hydrogen Kasi iyung mga hydrogen they usually bring electrons with them So kapag nag-lose ng hydrogen meaning nag-lose din ng electron T's kapag reduction naman po gaining hydrogen kasi yung hydrogen nga they bring extra electrods Okay In the case of oxygen naman sige Miss Legana So in the case of electron nasabi mo na in the case of hydrogen nasabi mo na in the case of oxygen naman sa oxygen naman po kapag oxidation nagge-gain po ng oxygen and then reduction naman po is losing oxygen Okay sige remind me to give you a one signature Okay Okay sabon ng salamin okay so nabanggit na yung free radicals and non radical oxidant Okay Can someone tell me kung paano nagkakaroon ng super oxide super oxide an ion sa electron transport chain sa mitochondria Kaya sir audible po ako Yes Ayan so ang nangyari po kasi ' ba yung sa ano po yung reactive oxygen species po is nagge-generate po siya sa ATC kasi ' ba sa ATC nangyayari which is sa mitochondria So inside ourselves doon po sa mitochondria nagge-generate po ng process through nga iyung oxidative phosphoration in etc wherein iyung oxygen is used as a final electron acceptor So normally po in normal metabolism iyung oxygen po nag-a-accept po siya ng four electrons T's nako-convert po iyun into water Pero sometimes po one electron lang po yung nafi-fix nung oxygen instead of forkia po nakakaproduce ng isang free radical antioxidant which is yung super oxide anion Ano po tot insular words po yung oxygen po kapag partially reduced po siya it generates po yung super oxide and instead po yung water Okay good thank you Kayla Okay Um O sige dito naman tayo Can someone tell me this sa radialysis of water Radialysis of water and everything Sige Miss Baltazar Sir clear ko lang po yung radiation Nagco-cause siya ng water radiolysis or explain po yang pinakagraph na yan Ay yung figure po pala Sorry po Ah yung ROS formation po So yung ROS formation po nag-o-occur po siya in three stages which is yung physical physico chemical stage at saka iyung chemical stage So during ano physical stage iyung ionizing radiation kapag nakipag-interact siya with water molecule um this interaction pwedeng mag-lead sa excitation or ionization Kapag excitation process this will produce an excited excited state water molecule And kapag ionization naman ah yung water molecule maglo-loose siya ng electron forming water cut ion and free electron So after that stage ah mag-o-occur na yyung physicochemical stage wherein yung um yung na-produce na excited water molecule magdi-dissociate siya into hydroxyl radical and hydrogen atom Tapos 'yung na-produce naman na water cut ion magre-react 'yun with water molecule tapos magpo-produce siya ng hydronium ion at saka ng hydroxyl radical And then yung free electron na na-produce sa ionization um ayun yung magiging solvated So kapag sinabing solvated or yung parang solvation ito yyung interaction between the solvent at nung dissolved molecule So in this case iyung solvent is iyung water molecule tapos iyung dissolved molecule is iyung free electron So iyung sa salvation nagco-occ which is yung thermalization free hydration at saka iyung salvation So first yung sa thermalization yung free electron mag parang magi-slow down magi-slow down siya kasi parang magco-collide siya with surrounding molecules tapos nata-transfer yung kinetic energy ah kinetic energy kinetic energy niya kaya ah parang bumabagal siya tapos during prehydration naman magiging fully trap bago siya maging fully trap yung electrod magi-interact na siya with water molecule tapos mage-enter na siya sa transent state So kapag sinabing transent state magta-transition na siya from free electron to salvat And during this process dito rin napo-produce iyung quasai free electron So kapag sinabing quasai free electron um it is not completely free but it is not also fully trapped And lastly savation naman dito na mangyayari yung electron magiging fully traped na siya into a lower energy state forming solvated electron So even though na hindi na siya longer free kapag uh solvated electron it remains chemically reactive So makakapag-contribute pa rin siya sa redox reaction tapos form ah forming 'yung mga hydrogen atoms at saka hydrogen ah peroxide So lastly sa chemical stage dito napo-produce yung mga products ng radiolysis which are yung hydroxyl radicals h hydrogen gas hydrogen peroxide super superoxide and ion hydroxide ion at saka 'yung hydroperoxyl radical anything very good okay missar remind me to give you two signatures in the next meeting very good so is that clear is that clear for everyone Next tayo Who is that Okay Sige next tayo So dito na tayo sa different um biological damage caused by ROS So nabanggit ko na rin naman to Um sige let's go na doun sa molecular mechanism of rose damage Okay Tadan Okay So dito tayo dito tayo Dito tayo next stop ' ba Okay So doon tayo sa um oxidative damage to DNA which is yung most common is yung formation of the um eight oxoguanine Okay Can someone tell me that again Paano nafo-form si 8 oxoguanin by ROS Miss Limpin um yung dito po nagi-start po yung reaction doun sa carbon 8 po ng purine ring So bale um yung anine ring ng ayan ng buwanin Okay go Ayan Tapos iyung hydroxyl radical po natin ' ba po highly reactive siya T's nag-i-interact po siya doon sa carbon 8 ng guanine Tapos ia-abstract niya yung electron from guanine Tapos yun yung magfo-form ng guanine radical natin And yung guanine radical natin unstable siya So yung radical intermediate na yon magi-interact siya doun sa molecular oxygen So magfo-form siya nung peroxyl radical na yung GOO Tapos 'yung peroxyl radical na 'yun um mag-u-undergo siya ng reduction Tapos yun yung magfo-form nung ating eight hydroxyuanine Tapos um yung eight hydroxyuanine mag-undergo siya ng totomerization um which is a kind of isomerization na um specifically yung ketol ketoinol na totomerization t's magfo-form siya nung eight oxoguanine Tapos um ang consequence nito um iyung eight oxoguanin natin magp-pare siya with um magiging siyang magmi-mispair siya with adenin instead of cytosine during replication So instead na yung tamang pairing po And yung mutation po na to is commonly na nakikita natin with cancer diseases Saan With associated po siya cancer Okay very good So thank you Miss Limpin So so ayun So bakit sa tingin niyo sa carbonate of the purine ring of the guanine uh base nag nakikipag-interact si hydroxyl radical Ano bang meron doun sa carbon 8 of the purine ring So ' ba si hydroxyl radical very reactive kasi meron siyang loan pair meron siyang ano meron siyang unpaired electron So kapag unpaired siya so like I need electrons So saan siya pupunta Doon siya pero pumunta siya doon sa C8 sa carbon 8 of the purine ring So bakit kaya Anong meron doon sa carbon of the purine ring Ano sa tingin niyo Miss Amil Um electrophilic po yung um ah CA po kaya po ah naghanap din po siya ng electron na magpreep So sila pong dalawa yung ganon prepare Okay Sige So it's electrophilic What else Thank you Missel Hindi naghahanap eh Hindi electrophilic eh Kasi hindi naman siya nag It's a stable structure but it would not seek ' ba would not seek or or like maghahanap ng isang ah ng hydroxyl radical ba so hindi siya electrophilic pero still that's a good idea Thank you Miss Amil Miss Navaro try lang po sir due to electronity density po ba parang may may mga electrons po si C8 that is ready for reaction po sir kasi mataas yung electron density ibig sabihin madaming ano um mataas yung electron density of the carbonate of the purine ring kaya doon siya makikipag-interact kasi doun yung mataas electron density and uhaw na uhaw nga si um hydroxyl radical sa isang electron Okay So kapag nag-undergo ng reduction si peroxyl radical ba kasi meron na kapag nag-undergo siya ng reduction it means nagkakaroon ng addition of what God electron po or h hydrogen po Okay nagkaroon ng addition of hydrogen kaya naging eight hydroxyuanine Okay So sige So nasa nabanggit ni Miss Limpin na ang biological consequence nga niya is that it mispairs with adenine instead of cytosine during replication So nagkakaroon ng mutation and frequently nagco-cause ng cancer So ano yung repair mechanism involved in um in the removal of 8 oxog or 8 oxoguanine Miss Pawal sir based excession repair po kung bale ano po ah gumagamit po siya ng 8 oxog DNA glyso ah glycillase or yung OGG1 po para po ma-recognize tsaka ma-remove po yung o yung 8 oxygen po sir Okay very good So it's the basicion repair or be using the enzyme OG1 or eight oxyg DNA glycosylates to recognize and remove eight oxoguanine Okay very good Okay so now let's go to the um other type of damage of Ross induced damage to the DNA which is yung cytine deamination So so now let's look at cytosine oxidation So instead of base pairing errors this leads to actual base conversions So so ba by steps din to So step one is yung ROS ' ba So iyung hydroxyl radical it attacks the cytosine specifically it attacks the carbon the fourth carbon and the fifth carbon or C4 and5 of cytosine forming a cytosine derived hydroxy radical So this intermediate is unstable and it rapidly loses an amine group Nawawala si NH2 converting cytosine into uracyl So nagiging uracy siya Uracel siya kaya tinatawag na base conversion So anong nagiging consequence nito So si uracil it pairs with adenine instead of guanine leading to C2T transition mutation So this is especially common in CPG islands which so regions of DNA reach in cytoscine and coanin which are crucial for gene regulation So ano naman yung repair mechanism dito So dito papasok si ano ano sa tingin niyo 'yung gin 'yung repair mechanism dito Ah Kea sir pwede rin po ba dito yung base exision repair Yes basic fictisition repaired din yan pero anong endim ano po instead po yung kanina ba po sa ano sa tawag doun yung doon sa G2P transversion which is yung sa etoxagoguan ginagamit po is OGG1 pwede po dito is yung UDG or yung Ung which is yung UCL DNA glycosillase para po for ano recognition and rem ano po removal po nung uracil by cleaving po nung glycydic bond Okay very good ' ba So yung un or yung ong enzyme okay yung uracy DNA glycosillates Okay So very good okay so clear tayo doon So another naman another DNA or Rost induced DNA damage is yung sim glycol formation So it and it causes replication blockage and mutagenesis So now let's move to timin So tapos na tayo kay kay guanin Tapos na rin tayo kay cytosin ' ba Ngayon naman dito tayo kay thin So unlike guanin or cytosine thimin oxidation doesn't cause me spiring but instead it creates replication obstacles Okay So si hydroxyl radical ulit ia-attack niya naman si timin pero this time sa carbon 5 and carbon 6 of timine forming a highly unstable dihydroxy intermediate So this intermediate rearranges itself into a stable timine glycol molecule So nagkakaroon ng form of timin glycol Now ano yung biological consequence nito So siin glycol it blocks DNA polymerase causing replication fork stalling So this can lead to both single stranded braks and double stranded bricks if not repaired Okay So now what is the repair mechanism So pwede nating gamitin si endonucleus 3 or si NHT1 and OGG1 which removes the stamin glycol via base exision repair Okay So now let's go to the final um rust induced DNA damage Nanghihina na ako Anong oras na ba Wala pa 5:30 ng dibdib ko Okay So yun yung is yung formation of a basic sites or AP sites So nagkakaroon ng naked DNA lesion So what happens naman if Ross completely removes a base So nagkakaroon tayo ng AP site So So again si hydroxyl radicals ba nga siya yung pinaka-dangerous and siya yung pinaka-reactive So si hydroxyl radical ngayon hindi na yung like carbon carbon ano hindi na yung carbons of the different bases yung ina-attack niya This time ang ina-attack niya is yung n glycosidic bond that links the base to the deoxy ribo sugar So kapag natanggal syempre si base this results in the complete removal of the base leaving behind leaving behind an apurinic or apyidinic AP site Okay So ano yung consequence nito Okay Ano yung consequence kapag may AP site Kapag meron kang a basic site ha Wait lang ha Wait lang nag-message wait lange ka ikaw pero wait lang Okay sige Keila ano yung sir kapag grabeung kapag po kasi may kapag po kasi may sorry po kapag may AP sites po kasi meaning wala pong pure or pyramiding base na nandun sa location na yon so pwede pong Kung mag ano maging consequence is hindi magtutuloy yung DNA replication as well as pwede pong mag-cause siya ng breakage especially kapag SSB po pwede po siyang ma-cause non as well as DSBS if ever na yung two AP sites po is located near each other Okay Magkakaroon ba ng stalling of the replication kapag may AP sites Pero still thank you Kayla Anong mangyayari kapag may AP sites Hindi siya magco-cause ng stalling eh Magco-continue siya eh Sige Miss Navaro Try lang po sir Ba sabi niyo po hindi mags-stop po yung replication Possible po na uh maging double strand brakes po 'yung single strand brak po Sir maging double strand brak How Paano siya magiging double strand brick Kapag nag ano siya kapag nag kapag nagkaroon ng AP site You have to remember that this is like removal of the base Okay So walang base pero intact yung um yung backbone ng DNA So anong magiging cause non Miss Limpin So ano pag nakita siya ng TNA polymerase Ah sir yung ano po mati-trigger po yung ano makikita po siya nung APNonleus tapos ika-cut niya po yung DNA strand para mag-allow for yung DNA polymeres na mag-fill doun sa correct base mo Ano again sorry ah ' ba po may makikita po siya na damage so may missing base po na basic site Tapos 'yung AP andonucleus po ika-cut niya po yung DNA backbone dun sa AP site para mag-create ng nick Tapos yung DNA polymeres po um gagamitin niya yung complementary strand para mag-add nung missing bases Bale pag na-recognize po parang ika-cut po t's fill Okay So nandoon na tayo sa repair mechanism So yun nga So gagamit ng AP endonuclease ' ba yung APE1 para magkaroon ng recognition and magkaroon ng repair through the um basicion repair pathway So ano muna ba yung biological consequence Ano ba yung biological consequence kapag merong AP site Kapag nagka-copy ka Kapag nagka-copy ka tapos nakita mo 'yung kina-copy mo may ano may sabi mo ano ba 'to Hindi ko maintindihan So like nag-assume ka ito na lang 'yung kinopy mo So anong mangyayari doun sa kinopy mo Um na-maintain ba yung fidelity Anong mangyayari Nagkaroon kasi nag-ano ako Nag-insert na lang ako eh Bibigay ako na Nagkaroon nag-insert ako ng random something Sabi ko "Ba't may butas dito Anong ba't may ba't may tapal 'to Anong mangyayari kapag may AP site Sige Miss Kantila Ayun 'di ba So APS are highly mutagenic You have to remember that magkakaroon ng mation because magkakaroon ng random based insertions 'Di ba kasi yung ginagawa ni DNA polymeries kapag hindi na-repair muna ni ano eh ni um APNucleas ' ba Ay naku nakalimutan Ay naku ' ba magkakaroon magkakaroon ng mutations kapag may apite kasi may blanco eh Like paano pag kinopy yun ni DNA polymer ano to ' ba Okay So yun ha Wait lang nagc Okay now let's go So ayun na yung mga ano um rust induced um DNA damaged So now let's go to Rust induce lipid damage Okay So So ang Ross ngas mention nga doon sa previous na slide ba it causes lipid peroxidation and membrane dysfunction So paano What's the molecular mechanism Okay So una is that si Rose inaattack niya si Pufa Okay So ano yung Pufa Polyunsaturated fatty acid Okay So membrane phospholipids contain unsaturated fatty acids with double bonds making them vulnerable to rose Okay So unang-una diyan is that si hydroxyl radical Okay So nagkakaroon ng abstraction of hydrogen Okay So si hydroxyl radical ba highly reactive siya and it abstracts hydrogen atom from the meseline group between the double bonds in a polyunsaturated fatty acid Okay So tinatanggalan niya ng hydrogen atom yung methyline yung methyline group ng two double bonds between the two double bonds in a polyunsaturated fatty acid So now this leaves behind a lipid radical Okay So kapag lipid radical meron siyang un meron siyang unpaired electron ba that stabilizes the fatty acid chain Paano Okay So this lipid radical so step two is the oxygen incorporation or formation of the lipid peroxyl radicals Excuse me So this lipid radical reacts with molecular oxygen O2 forming a lipid peroxyl radical or LOO So this lipid peroxyl radical ngayon naman is it that steals electrons from the neighboring lipids kasi nga radical siya eh 'di ba So ibig sabihin nagi-steal din siya ng electrons So now it steals electrons from the neighboring lipids propagating a chain reaction So nagkakaroon ng chain reaction ngayon Pag nag-steel magiging lipid ah magiging lipid radical magi-steabi Okay So next naman is yung propagation So peroxylal radicals ini-spread niya yung damage by causing a chain um chain reaction nga So once formed lipid peroxyl radicals drive a self-sustaining chain reaction So nagkakaroon ng So next na step is yung formation of lipid hyper hydroperoxides or LOOH So the lipid peroxyl radical or LOO abstracts a hydrogen from another fatty acid forming a lipid hydroperoxide and a new lipid radical So this process continues damaging multiple lipids in the membrane So nage-gets ba So si Rose inattack niya yung isang um nag-abstract siya ng hydrogen Nag-abstract siya ng hydrogen doon sa bond between two um polyunsaturated fatty acid Now after this ang resulting molecule nito is yung lipid radical Now this lipid radical reacts with molecular oxygen Okay So this lipid radical reacts with the molecular oxygen which then forms a lipid peroxyl radical Okay Ito naman ngayon si lipid peroxyl radical kukuha siya ngayon ng hydrogen from another fatty acid doon ulit sa methyline group So magpo-form siya ngayon ng lipid hydroperoxide which is LOOH and also lives a new lipid radical kasi kumuha siya eh yung pinagkuhaan niya naging lipid radical ngayon So this process continues damaging multiple lipids in the membrane So ano yung biological consequence nito Okay So ibig sabihin nawawala unang-una diyan is yung nawawala yung fluidity ng um phospholipid membrane So lipid peroxidation disrupts the tight packing of phospholipids making membranes more rigid and leaky So nawawala din yyung selective permeability So oxidized lipids change the hydrophobicity of the membrane leading to ion leakage like um um divalent calcium or like um sodium ion and nagco-cause yun ng osmotic stress kasi nagkakaroon ng ano eh imbalance eh nagkakaroon ng imbalance between the outside um solute concentration and the inside solute concentration nagco-cause ng osmotic stress Excuse me And syempre ang pinaka-cause is 'yung syempre magkakaroon ng membrane protein dysfunction So lipid oxidation modifies integral membrane proteins impairing receptors and transporters Miss Cantilla So let's go to step one ulit nagugutom So doun lang sa part na yon hindi ko na uulitin Okay So ang nangyayari is hydroxyl radical um it abstracts Kumukuha it steals It steals a hydrogen atom from the mesheline group between two double bonds in a polyunsaturated fatty acid So ngayon because nga nag-abstruction siya ng hydrogen this leaves behind a lipid radical which causes a chain reaction Okay Okay Okay Sige So hindi lang doun natatapos yung damage Hindi lang doun natatapos yung Hindi lang doun natatapos yung chain reaction ni lipid radical ng formation ni lipid radical Lipid peroxidation doesn't just damage membranes Okay It also produces toxic byproducts Nag nagco-cause siya ng production or formation of cytotoxic aldehydes which is ayan nga si um MDA and H& Okay So lipid hydroperoxides or LOOH undergo fragmentation So kapag um nagkakaroon ng cleavage of the lipid hydroperoxide So nag-undergo siya ng ah fragmentation which breaks down into two Okay So yun nga si Malondi aldehyde and C4 hydroxy 2 nonenal um nonenal um aldehyde or HNE Okay So si um MDA it is a highly reactive aldehyde that cross links proteins and DNA While si H&an this is an electrophilic lipid that modifies proteins and signaling pathways Now paano sila naging cytotoxic So it causes protein cross linking So MDA or maldehyde it reacts with lycine arginine and hisin in proteins forming covalent aducts that inactivate this enzymes or the enzymes na nagbibilong na merong lycine arginine and hisine Also nagco-cause siya ng DNA mutagenesis So maldehyde or MDA forms also hindi lang siya nagfo-form ng covalent aducts of proteins Nagpo-form din siya ng DNA aducts like M1DG or Pimido Pyrimido purinone aducts leading to mutagenesis So nagkak nagco-cause din siya ng ah mutation and also nagdi-disrupt din siya ng signaling pathways So si HNE kasi or si four hydroxy 2 nonenal um it binds 'di ba to to um to 16 residues in proteins altering enzyme activity and it triggers apoptosis Okay So yun yung cause yun yung um damages that is done by lipid peroxidation So like it's very very chaotic talaga 'di ba Kasi kapag nasira na 'yung membrane mo patay ka na wala ka na 'di ba Like kasi magli-leak na lahat 'di ba May papasok na kung anik-anik tapos magpu-putos pa ng ano cytotoxic na aldehides from the cleavage of the lipid hydroperoxides So lipid peroxidation talaga is very chaotic which so and lipid peroxidation is caused by ROS Okay Now sakit na ng ano ko Wait nga lang Now let's go to protein oxidation and carboxylation So dito na tayo sa rost induced damage Um rost induced protein damage Okay So si Ross naman ngayon ay inaattack niya naman directly na directly niya ng inaat si amino acid chains So kapag inattack niya syempre it modifies the protein structure and kapag namodifies the protein structure magkakaroon din ng modification of its function Okay So so unang-una diyan is yung protein oxidation So kapag nagkakaroon ng enzym inactivation So step one is yung oxidation of cistin and methyonine Okay So cistin oxidation leads to sulphenic sulphinic and sulphonic acids which irreversibly inactivates protein So sulphenic SOH sulphinic SO2H and sulfonic SO3H Okay So this um inactivates proteins irreversibly Also um kapag naoxidize si it forms um disulpide bond Nagkakaroon ng disulpide bond formation leading to protein misfolding and aggregation So nagkakaroon ng aggregation of protein or nagkakaroon ng protein flux Okay While yung methonine oxidation naman um kapag naoxidize si methyonine nagpo-produce naman to ng methyonine sulfoxide Okay So ito si Cisin na si methyanin ba nagco-contain siya ng ano ng SH groups Okay So kapag naoxidize si methyonine nagco-cause siya ng methyonine or nagre-result siya into methyonine sulfoxide which alters again protein stability Okay So why does this cause enzyme inactivation So unang-una is yung um active s disruption So many enzymes rely on 16 for catalysis and oxidation Kapag nagkakaroon nga ng sulphenic sulphinic and sulphonic Kapag na-oxidize si 16 nagkakaroon ng inactivation of this active sites Kapag nagkaroon ng um inactivation or um changes in the active sides of this um enzymes For example yung protein thyrocine phosphatasis ibig sabihin na na nagkakaroon ng changes nai-inaactivate siya So hindi na siya nakakapag um perform ng function niya Also it causes nga misfolding and aggregation So na-mention na naman natin before sa virology class na sa virology lecture natin na masama ang protein aggregation Okay So disulf bonds form abnormal protein structures leading to protein clumping So kapag nagkaroon ng protein clumping anong magkakaroon So it's mostly seen in Alzheimers and Parkinsons Okay And also magkakaroon ng loss of protein protein interactions So oxidation prevents proteins from forming proper signaling complexes Kasi nga nadagdagan eh Ibig sabihin hindi siya hindi na siya magkakaroon ng uh hindi na siya makakapag-bind hindi na siya makakapag-contact sa mga other protein complexes in the cell Okay So yun yung protein oxidation Now let's go to protein carboxylation or protein carbonylation Okay So um ang nangyayari dito um basically is that it marks the proteins for degradation by the protee Okay So sa protein carboxylation dito nage-enter yung proteosomal um degradation or proteosomal targeted degradation Okay So step one So si carbonl group ay naa-add do sa proteins So si Rose it attacks amino acid such as arginine lcine histodidine and threonine So kapag inattack ni Rose si Argenine Lcin histodidine and threayon it leads to carbonyl formation or yung COH ' ba So carbonated proteins become proteosome targets Carbonyl groups create abnormal protein confirmations which are recognized as damage signals by the 20s proteosome Okay So the proteosome degrades oxidized proteins preventing accumulation of nonfunctional proteins So ano namang consequences ng carbonylation or carboxylation So it nagkakaroon ng loss of function ' ba So carbonylation disrupts protein folding and enzyme activity Also nagka-cause ng proteosomal overload So excessive oxidation overwhelms the proteosome leading to protein aggregation So syyempre kapag attack ng attack si Rose doon sa um sa amino acids na nagpo-form ng carbonyl so ibig sabihin mare-recognize na mare-recognize si proteosom 'yun mapapagod si proteos sabi kagod naman to so manghihina si proteosom Kapag nanghina si proteosome magle-lead ngayon 'yun sa protein aggregation because wala ng nag-degrade sa mga um nonfunctional misfolded and unfolded proteins that would cause aggregation So kapag nag-cause ng protein aggregation ano yung magiging biological damage niya Neurodegenerative disease Okay Now kapag nagkaroon din ng accumulation of oxidized proteins it activates P53 Okay Kapag na-activate si P53 ' ba meron siyang tatlong pwedeng gawin Um senescence um repair or apoptosis So dito kapag na-activate si P53 because of um um accumulated or high accumulation of oxidized proteins it promotes cellular aging or senesence lang Ibig sabihin hindi na pwedeng mag-divide itong cells na to pero metabolically active pa siya Okay So yun yung nagiging um so yun yung um causes ng yun yung nagiging um ano bang tamang term Yun yung rust induce protein damage Okay Sino naman 'to Okay So so ayun Sige I got to happy -CIT I'm looking at the figure Eh Should I discuss this pa or discuss na Um are you guys naman you guys familiar pa ba with like um single stranded bricks and double stranded bricks and kung bakit siya tama And what are the repairs for it Okay wala ng nakikinig Sige recitation tayo Okay So anong nangyayari sa lipid pero oxidation Rust induced lipid peroxidation Miss Limpin sir dito po sa Ross na induce lipid damage yung Ross po natin ina-attack po niya yung PUFA which is yung polyunsaturated fatty acid which is vulnerable po sa ROS kasi um meron po siya nung double bonds tapos tinatanggalan po ni Rose ng hydrogen group iyung methyline group ng pofa and yun yung nagle-leve nung lipid radical which is meron siyang unpaired electron na nagde-destabilize nung lipid chain Ang nangyayari po kasi yung lipid nagre tapos po yung lipid magre-react siya with molecular oxygen na nagfo-form nung lipid peroxyl radical So yun po kukuha siya ng hydrogen for with another fatty acid which also causes yung um formation po nung hydroperoxide natin and another lipid peroxyl radical Yung mechanism po nung damage dun sa um membrane integrity is that yung mga lipid radicals po kasi natin dahil unstable sila nagi-steal sila ng electrons dun sa neighboring lipids nila So um because of this nagpa-propagate po 'yung chain reaction nng pagkuha nng mga electrons and hence nadi-disrupt po nito 'yung tight packing and nawawala po 'yung permeability nng cell membrane natin which also causes 'yung ion leakage And yung ion leakage pwede po yung mag-cause ng osmotic stress because of the imbalance po ng mga ions natin And possible din po na ma-modify nito yung integral membrane proteins natin masisira yung receptors and yung mga transporters na responsible po for the functioning po ng cell Thank you Miss Limpin What else Yung ano yung other than disrupting the membrane ano pa yung ginagawa niya Ito What are these Miss Kantila Akala ko hindi ko po masyadong naintindihan Okay Sige sige Thank you Miss Kantila So anong nangyayari dito Why is um lipid damage so chaotic other than um membrane damage Ano pa yung ginagawa niya ha anyone Anyone Sige Miss Toma Sir try lang Ito po ba yung ano dahil po doun sa may decomposition po ng lipid hydroperoxides which forms po ng mga secondary products like malon dialdehyde or mda we have the four hydroxytone nononenal and acryuline and isoprostanes and itong mga secondary products po na to meron po silang decomposition ano po hindi decomposition decomposition ba na decompose ay sorry anong nangyayari Ari yun na po yung ko sure Fragmentation Nag-undergo siya ng fragmentation Nagfa-fragment siya Nagkakaroon ng cleavage So yung lipid hydropedoxide nagiging ayun na Sige go Yung lipid hydropedoxide kapag nag fragmentation it would break down into yung mga secondary products po na nabanggit ko po kanina which is MDA yung for H& isoprestines Okay Anong kino-cause noon Why is it destructive UM UMDA po sir pwede po siyang mag-cause ng DNA damage So Uda po pwedeng mag-form ng like DNAs particularly po with iyung guanin basis Kaya nagfo-form din po siya ng umions and mutations po Pwede rin po siyang mag-disrupt nung membrane Like pwede po niya i-alter 'yung phospholipid by layer ng cellular membranes Yung sa 4 HNE po pwede rin niya pong madisfunction yung mitochondria mismo So pwede po siyang mag-accumulate sa mitochondria and impair po 'yung function niya For acrulane po yung nanood ko dito Pwede po yung ah yun pwede po siya sa neurotoxicity So pwede po siya sa ah pathogenesis ng neurogenerative diseases like Alzheimer's disease and Parkinson's disease And yung sa isoprostate naman po sir ayun na po hindi ko na-note Pero pwede po ba siya doun sa inflammations like sa mga hypertension and vascular dysfunction Ayun po Okay Sige sige sige So thank you Miss Doma for that for also an additional information So thank you Okay Now let's go to protein um protein damage Rost induce protein damage So what are the mechanisms there Lima lang ba estudyante ko Gagawin ko ngang 40% recitation 10% lang yung quiz Um Miss Kantila naman Very good Thank you Miss Cantilla Okay So in the next meeting we'll move on saages molecular mechanism damages in um SSB uh or SSB damages and DSB damages and also um the repairs that are involved okay and the different cellular consequences of ROS and also um um the benefits ba yung beneficial um beneficial uses of ROS kung para saan siya ginagamit sa cell kasi as we have mentioned kanina ROS is naturally produced by our cells ' ba for signaling for um passage and destruction okay So sige we'll move to that We'll move we're gonna go into that in the next meeting Okay So for now um ah sige So medyo nawalan ako ng gana because parang limang estudyante lang yung kausap ko kaya sige let's move on na lang sa next meeting So very good sa mga nagre-recite So may nag-note ba ng mga nag-recite ngayon president or si Miss Dali Are they here ba muna Sir Sir hello po Hello President Yes po sir No-note po Okay sige send mo sa akin ha para like mannees ko kasi ano eh So ayun ha Babaguhin ko yung ano computation of rate ha Tataasan ko yung recitation So ayun lang See you next meeting Goodbye