Module 11 Red Blood Cells PDF

HEMATOLOGY 1 LECTURE | 3RD YEAR | FIRST SEMESTER BATCH SORBETES ‘25 MODULE: 11 RED BLOOD CELLS 11.0 RED BLOOD CELLS MEMBRANE COMPOSITION...

HEMATOLOGY 1 LECTURE | 3RD YEAR | FIRST SEMESTER BATCH SORBETES ‘25 MODULE: 11 RED BLOOD CELLS 11.0 RED BLOOD CELLS MEMBRANE COMPOSITION MORPHOLOGY The majority is protein, followed by lipids and your carbohydrates Size: 6-8um PROTEIN Color: Salmon Pink (because of the heme portion of the Hgb 50% PROTEIN (Rodak: 52%) Shape: Biconcave Disc Majority is your protein component which is half or ○ (Discocyte or donut shape because 52% according to rodak. In general 50% of the there is a central concavity and it is membrane composition of your RBC is protein actually an important feature of RBC) Divided into 2 Average surface area: 140 um2 Recall on the structure of the cell, you know that our cell membrane is actually described as a phospholipid bilayer SIDENOTES: Dun lang tayo sa cell membrane (sa outer of RBC). And you that cell membrane is a phospholipid bilayer, meaning ★ More hemoglobin is found on the outside of the it is composed of phosphate heads, w/ 2 fatty acid tail. cell and for that reason, a normal erythrocyte stains Kaya nga siya bilayer kasi meron kang inner layer and pink to red on the outside with a pale area in the outer layer, both of them are composed of phosphate head center. and fatty acid tail Kaya siya phospholipid bilayer, it is 2 layers of ○ because from our previous discussion more phospholipid concentration ang Hgb sa gilid. Tapos as you Ano yung nas agitna nila? Meron kang cholesterol actually, go inside or at the central area, nag l-less meron tayong tinatawag na fluid mosaic model, yung intense yung concentration ng Hgb. cholesterol na yun is parang siya yung nag m-maintain ng ○ Kaya parang siyang nag c-concave dun sa magandang flow lang sa cell membrane. Siya rin nag center. Kaya nagiging biconcave yung shape mmaintain ng tensile strength. Parang ito yung spring ng niya because of that cell membrane ○ BTW, Since the Hgb will hold your O2, more ng RBC. Kaya O2 is more concentrated in the outside part or para if ma press, at least the peripheral part of RBC. meron kang ★ The biconcave shape of erythrocyte allows for spring na maximum surface contact of hemoglobin within deformable. the cell, thus greatly facilitating the exchange of That is the role blood gases. of the ○ Nagiging itsura siya ng biconcave because of cholesterol the distribution of the Hgb, which is different in If lumagpas ka the periphery and also as you go centrally or na sa 2 layers the inside of RBC of phospholipid na sa loob niya ★ This shape allows red cells great flexibility and is cytoplasm. elasticity (pliancy) and allows them to be folded when they move through very narrow blood Now na saan ang mga trans membranes or trans capillaries (a property called RBC membranous proteins or integral proteins? (binasa ni DEFORMABILITY.) sir yung statement para intense) ○ Ibig sabihin they are flexible enough, since we know or you know your blood vessels can be A. INTEGRAL (TRANSMEMBRANOUS) various sizes, depending on the location, Ito yung mga integral proteins na nag ttravers or nag especially if you are in the peripheral t-transition or nag t-transit sa buong surface or buong cell circulation. You know that your capillary has membrane ng RBC the smallest diameter, in order for them to slip a. Serve as transport and adhesion sites and through in the narrow aperture or narrow signaling receptors blood vessels, of course they also have to b. Support carbohydrate-defined blood group adjust with the size of the lumen or luminal antigens (ABH, MNSS etc. diameter. This property is known as c. Sialic acid (contains in the glycophorins in the CM DEFORMABILITY and this is attributed to the of RBC) shape of the RBC i. SIALIC ACID causes the negative ○ Of course with some structures that are charge of RBC. well not only RBC but present in the, w/i or inside the RBC also the other cells in our body because Sialic acid will create a cloud of anionic charged which is known as zeta potential (a cloud of anionic or negative charged) kaya negative yung charged ng RBC at makikita mo ito sa integral proteins or TRANSMEMBRANOUS 1 | LIM, JULIANA NICOLE B. │TORES, ANGELICA  BATCH SORBETES ‘25 d. Balikan yung phospholipid bilayer, so mga integral proteins or transmembranous proteins will traverse both inner and outer layer of the RBC phospholipid layer. (check the pic for better understanding) e. Sila ay mga channels or receptors or isipin as antenna yan. f. Kung sinabi mong channel, daanan ito ng tubig, calcium, potassium, sodium, nutrients. Daanan papasok at palabas kasi para silang mga “gates”. Ang tawag sa mga gates na iyon ay integral proteins or transmembranous g. If hindi naman sila channels or daanan, kung ano mang kailangan pumasok or lumabas sa RBC, sila rin ang mga receptors or mga antenna. Malamang attracted din ang RBC kung saan man siya pumunta or di kaya naman antenna ito para may mga ma-aattract papunta kay RBC. Mga receptors. h. And dito rin mga nakadikit ang mga blood antigen, kaya kapag mag bblood typing, saan part ng RBC makikita ang antigen, na dinedetect during forward typing or blood typing? Makikita mo lang siya sa surface. Syempre common sense, kapag na sa loob or kaila-ilaliman ng RBC ang antigen edi ang hirap niyang ma detect because its like “its buried” deep w/i the RBC. So it's easier for these antigen to be detected if its outside the RBC. Kaya nasa labas ang ating blood antigens (e.g A or B antigen) Just like he mentioned from our previous discussion, marami tayong mga blood type hindi lang si ABO. And andito makikita w/i your integral protein which is located in your cell membrane. i. Pwede ring channel, pwede ring dumadaan dito si glucose, kasi source siya ng nutrient ng glucose. Pwede ring gas, CO2 exchange. So, ito yung kanilang lagusan j. Examples of integral proteins are depicted on the table. For the table, the names and properties of selected transmembranous RBC Transmemembrane Band Molecular Copies per % of Total Function Protein weight (D) cell (x10³) Protein Aquaporin 1 Water transporter You have Aquaporin 1, from the term itself “Aqua”, meaning daan ito ng tubig. Labas masok ang tubig sa RBC Band 3 3 90,000-102,000 1200 27% Anion transporter, supports (anion exchanger 1) ABH antigens From the term itself, anion Nag c-carry din saw siya ng exchanger. What is anion? a negatively charged ion. Dito mga antigens, it supports ABH lumalabas masok ang mga antigens negatively charged electrolyte Crossover to BB, the band 3 or or ions, sa band 3 which is anionic exchanger 1 is the also known as anionic exchanger 1. carrier for DIEGO ANTIGENS, which is also a blood type Ca²+ ATPase Ca+ transporter Sabi nga ni sir, daanan ito. Daanan ito ng tubig, calcium, or mga anions and negative charged. Ang tawag sa kanila collectively ay integral or transmembranous proteins. Depende kung ano yung mga iyon, may kanya kanya naman silang mga pangalan Duffy 35,000-43,000 G protein-coupled receptor, Also a blood group, na supports Duffy antigens makikita mo lang rin sa surface Glut-1 4.5 45,000-75,000 5% Glucose transporter, supports glucose transporter 1 or type 1 ABH antigens Edi syempre kailangan ng RBC ang glucose for their energy. Kaya kailangan pumasok si glucose para ma metabolize ng RBC. Saan siya dumasaan? sa Glut-1. Ano classification ni Glut-1? an integral proteins. 2 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 Glycophorin A PAS-1 36,000 500-1000 85% of Transports negatively charged glycophorins sialic acid, supports MN determinants Glycophorin B PAS-4 20,000 100-300 10% of Transports negatively charged glycophorins sialic acid, supports Ss determinants Glycophorin C PAS-2 14,000-32,000 50-100 4% of Transport negatively charged glycophorins sialic acid, supports Gerbich system determinants Dito mo makikita ang sialic acid, sa Glycophorin. Whether it is A, B, or C. Again, ano ginagawa ni Sialic acid? It would make your RBCs negatively charged cells because it creates your clouds of anionic charged which is known as ZETA POTENTIAL. Dito mo rin makikita ang ibat ibang Blood type. Glycophorin A – Makiktia mo dito yung MN antigens, blood type rin yan Glycophorin B – Ss antigen (blood type rin) Glycophorin C – Gerbich (blood type rin) Mga iyan ay mga Blood type kaya huwag niyong e-narrow lang iisa lang ang blood type. Nag kataon lang na most significant kasi ang ABO and very important siya in transfusion medicine. Kaya parang siya yung na highlight lang na parang mga blood type, but there are a lot of blodo tpyes ICAM-4 Integrin adhesion An integrin adhesion para dumikit or pandikit Also the carrier of landsteiner kumabaga wiener (also an antigen) Adhesion protein K+- Cl- cotransporter Alam na ito, potassium, chloride Kell (blood type) 93,000 Zn2+ binding endopeptidase, Kell antigens Kidd (blood type) 46,000-50,000 urea transporter meaning si Kidd is a channel kung saan nag lalabas masok si urea Kaya if ikaw ay walang kidd antigen, walang daanan si urea. That is why if you are to treat your RBC w/ urea, pag sobra sobra ang urea nasisira ang RBC. but when the RBC lacks the kidd antigen, common sense, walang daanan si urea. And dahil walang daanan, syempre kahit mag dagdag ka ng urea, hindi naman siya makakapasok sa RBC, kasi wala siyang channel or gate kasi null or absent ang kidd antigen. That is why px or individuals that lack the kidd antigen are resistant to urea lysis or resistant to urea tx Na+, K+ -ATPase Na+, K+ -2Cl- cotransporter Na+, -Cl- cotransporter Na+, -K+ cotransporter Rh 30,000-45.500 D and CcEe antigens Mga blood type rin ito. RhAG 50,000 Necessary for expression of D This is a protein that is needed in and CoEe antigens; gas order for the RH ANTIGENS TO BE transporter, probably of CO2 EXPRESSED. That in the absence of RhAG proteins, even if you have inherited the RH genes, your RH antigens won't be expressed or will not be present in your RBCs because inorder for RH antigens to be expressed in your RBC membrane, they must be associated with RhAG protein 3 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 B. PERIPHERAL (SKELETAL) LIPID a. Proteins that localize to the interior surfaces of 40% the membrane A. OUTER LAYER b. Because the skeletal proteins do not penetrate the a. Phosphatidyl choline, Sphingomyelin, bilayer, they are also called peripheral proteins. Glycolipid c. Includes Spectrin and Actin B. INNER LAYER d. Kung trina-traverse niya yung buong phospholipid a. Phophatidylinositol, Phosphatidylserine, bilayer, both inner and outer, ang tawag dun is integral Phosphatidylethanolamine protein Remember basta Phosphatidyl palaging inner, e. Pero kung hindi niya pine-penetrate yung kabuoan ng EXCEPT Phosphatidyl choline outer and inner layer, ang tawag dun is PERIPHERAL lahat ng Phosphatidyl ay inner layer , EXCEPT f. Kadalasan sa may inner layer sila, basta hindi nila trinatraverse yung buong kabuoan ng phospholipid Phosphatidyl choline bilayer Matik si Sphingomyelin and Glycolipid ay outer g. Skeletal meaning more on structural components sila ng layer RBC that will maintain its structure kaya SKELETAL proteins ITO ANG GUSTO KONG EMEMORIZE OR TANDAAN SIDENOTE: si PHOSPHATIDYLSERINE because si Phosphatidylserine is the only NEGATIVELY charged ➤ HEREDITARY SPHEROCYTOSIS: Autosomal phospholipid that redistribute or flips to the other layer dominant; Associated with mutations that affect the integrity of band 3 (an example of integral protein. your SIDENOTES: anionic exchanger. the carrier of diego antigen) , RhAG (also a transmembranous protein. This is required in the ★ The cholesterol content of the membrane depends expression of RH antigens) , ankyrin (a peripheral upon the concentration of the plasma cholesterol, protein), protein 4.1, or spectrin bile acids and the activity of the enzyme meaning HEREDITARY SPHEROCYTOSIS is a defect Lecithin:Cholesterol Acyltransferase (LCAT) in both transmembranous proteins as well as ★ Abnormalities in the Red cell membrane: peripheral proteins ○ Increased cholesterol and phospholipid If there is a defect, madali lang mag kakaroon ng lysis content of the membrane: TARGET CELLS And the hemolysis is intrinsic or intracapsular Take note, the target cells (bullseye appearance), hemolysis there's a thin peripheral reme of hgb and then ○ Intrinsisc meaning, a natural part of the RBC. there's a less intensity as you go inside or to the And yung mga associated mutations of this center but there is a central condensation of hgb affect are all natural part of RBCs, as such the One clinical hallmark of thalassemia, w/ a presence of sickle cells hemolysis is an intracapsular hemolysis or ○ Abnormal L/S ratio: Acanthocytes intrinsic or intracellular defect L/S: Lecithin sphingomyelin ➤ HEREDITARY ELLIPTOCYTOSIS (OVALOCYTOSIS) ○ Abnormalities in the peripheral proteins: arises from one of several autosomal dominant mutations Elliptocytes, Spherocyte affecting spectrin dimer-to-dimer lateral bonds or the spectrin- ankyrin-protein 4.1 junction (or simply the ★ CHOLESTEROL confers tensile strength to the lipid spectrin. It’s a defect in peripheral proteins). bilayer In hereditary elliptocytosis, the membrane fails to ○ dba sabi ni sir, siya yung dumadaan sa may outer and inner, in between them, kaya fluid “mosaic” yung model rebound from deformation, and RBCs progressively natin ng cell membrane elongate to form visible elliptocytes, which causes a mild ○ CHOLESTEROL yung tensile strength or parang to severe hemolytic anemia “spring” ng ating cell membrane na double phospholipid Dba you have a property known as deformability. Which bilayer is the ability of the RBC to become flexible or elastic as ★ PHOSPHATIDYLSERINE, the only negatively they pass through the different narrow linings of your capillaries charged phospholipid, redistributes(flips) to the unfortunately HEREDITARY ELLIPTOCYTOSIS, once outer layer. ○ Dba na sa inner layer siya, na e-imagine niyo si they deformed, they can’t revert to their original phospholipid bilayer, may outer at may inner. Sa inner shape. nandun si Phosphatidylserine, siya lang ang negatively Dba parang sisingit sila sa mga maliliit na BV, kaya charged phospholipid. Na nag r-resdribute daw siya to parang mag e-elongate sila para mas numipis sila at the outer layer. So nag f-flip siya into the outer layer. mag kasiya sila dun. unfortunately, they are not able Kaya nakaka contribute rin siya sa negative charged ng to rebound from deformation, kaya nagiging RBC, apart from sialic acid elongated sila ang tawag dun is elliptocytes (hindi na ○ sialic acid and Phosphatidylserine, sila ang dahilan kung discocytes yung kanyang shape) elongated na siya bakit negatively charged ang ating RBC. kaya tinatawag na cigar shape (cigarette shape or oval) ○ Na ganun din sa mga platelets, may Phosphatidylserine kaya OVALocytosis kasi oval in shape siya rin ang mga platelets pag dating sa hema 2. Kapag na Anong cause nito? INTRINSIC, kasi ang problema mo aactivate raw ang mga platelet, the Phosphatidylserine ay peripheral proteins na ang proteins na ito ay intrinsic from the inside will “flip” to the outside. In order for the part of RBCs platelet to become more negatively charged particles. 4 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 So that your coagulation factors will be attracted to the platelets upon their activation, specially your calcium, kasi positively charged particle siya so opposite attracts, kaya ma aattract siya dun sa negatively charged na platelet. Which will become your nucleation site or coagulation cascade ★ Splenic macrophages possess receptors that bind PS and destroy senescent RBCs ○ receptors for Splenic macrophages, kasi kapag mamamatay na or those RBC that have already lived their 120 days lifespan. Dadaan sila sa reticuloendothelial system, which is composed of your liver and spleen and then they will be sequestered their (destroyed) via your macrophages sa spleen (littoral cells), liver (kupffer cells). They will destroy the senescent RBCs ○ Kapag sinabi mong senescent RBCs, it is RBCs that already live their 120 days lifespan. Kaya ma ddestroy na sila. ○ Ano yung mechanism? Extravascular or intravascular? Imagine it is from the outside of the blood vessels, saan? sa reticuloendothelial system or sa mononuclear phagocyte system in the liver and spleen. that is why it is EXTRAVASCULAR HEMOLYSIS CARBOHYDRATES 10% (Rodak:8%) Ito yung molecular structure or cell membrane ng RBCs. This is very complicated by the way this is from Rodaks (Look sa picture) Basta ito yung cell membrane mo. Yung outer layer and inner Representation of the human red blood cell layer, Traversing the membrane (yung mga membrane. The transmembranous proteins assemble transmembrane proteins sa pic). Dba trina in one of two complexes defined by their anchorage to traverse niya yung both inner and outer (yung skeletal proteins ankyrin and 4.1. Band 3 is the most sa may band 3, binilugan ni sir) tawag mo dun abundant transmembranous protein. In the ankyrin is transmembrane proteins or integral proteins. complex band 3 and protein 4.2 anchor to ankyrin, Ano yang mga yan? mga channels, nandito rin which is bound to the spectrin backbone. In the 4.1 nakadikit yung mga antigens, like diego complex, band 3, Rh, and other transmembranous antigens. proteins bind the complex of dematin, adducin, actin, Sa may band 3 nandito si diego antigens. tropomyosin, and tropomodulin through protein 4.1. Naka incorporate rin si Rh, si RhAG, GPA CD47, signaling receptor; Duffy, Duffy blood group (MN antigen; GPB si Ss antigen; GPC si system protein; GPA, glycophorin A; GPC, glycophorin gerbich antigen) , LW (dba ang carrier is si C; Kell, Kell blood group system protein; LW, ICAM4) Landsteiner- Wiener blood group system protein, Rh, And you also have others like your kidd Rh blood group system protein; RhAG, Rh antigen antigen is your urea. Ano yung Glut-1 expression protein; XK, X-linked Kell antigen transporter? Glucose transporter. Basta expression protein (Rodak)Page.118 tandaan, either channels yan, receptors, or mga blood antigen (balik ka sa pic) sa may inner layer, nandun ang serpentine structure (yung red na parang snake sa pic) yun ay spectrin. nandiyan si spectrin, which is a peripheral protein. Pag sinabi mong peripheral protein, btw si ankyrin nandun lang din (sa pic sa baba ng band 3). Mga peripheral protein, na hindi nila trinatraverse yung buong phospholipid bilayer. Nandun lang sila sa may bandang inner layer 5 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 METABOLISM OF RED BLOOD CELLS Generates 2 moles of ATP per glucose molecule We have 4: ○ Originally apat, kaya lang yung dalawa ay na 1. EMBDEN-MEYERHOF PATHWAY consume in the process kaya dalawa ang gain 2. HEXOSE MONOPHOSPHATE PATHWAY mo, generate or net mo 3. METHEMOGLOBIN REDUCTASE PATHWAY Glucose catabolism is catalyzed by the enzyme 4. RAPOPORT-LUEBERING PATHWAY Pyruvate Kinase ○ Pyruvate Kinase so ito yung parang rate limiting EMBDEN-MEYERHOF PATHWAY enzyme sa ating glycolysis Energy production via Anaerobic Glycolysis, ○ Pyruvate Kinase does it ring a bell? dba during the absence of O2. In fact this is the most predominant discussion of hemolytic anemia, one also cause pathway for the metabolism of RBCs kasi (90% intrinsic defect is enzyme deficiency, example glycolysis in the red cells follows EMP) Pyruvate Kinase deficiency. Remember our RBCs do not have nucleus as well ○ What did doc tell us before? Pyruvate Kinase is as mitochondria “powerhouse of the cell” meaning an enzyme needed in the energy production of its the house of energy. However your RBCs do not RBCs. So w/o Pyruvate Kinase there is no have mitochondria. Matalino naman ang panginoon, it's enzyme that will catalyzed the metabolism or just about the utilization, Which is a lesson for all of us. Kung breakdown of glucose as the energy source of may hindi binigay sa panginoon sayo, may binigay siyang iba RBCs, kaya wala silang pag kukuhanan ng na dapat e-utilize mo and make the best out of it. Marunong energy, anong mangyayare? patay, hemolysis. tayong makuntenta kung anong meron tayo, you have to Ano ang kaniyang cause? INTRINSIC DEFECT given you☺️.😇 cultivate it and become the best version of what god has Parang RBCs, wala silang mitochondrias so walang because of pyruvate kinase deficiency an enzyme that is intrinsic to the RBC power house of the cell, pero merong remdyo or Now recall our biochemistry, ito yung nangyayari. meron pa ring binigay para meron silang pag Simply glycolysis kuhanan ng energy. Without mitochondria, the RBC is left to rely on glycolysis for energy production. Fortunately, oxygen exchange and oxygen binding to heme iron do not require energy Now, bakit nangangailangan ng energy ang RBCs? Said dito sa table BOX 9-1 Erythrocyte Metabolic Processes Requiring Energy ★ Maintenance of intracellular cationic electrochemical gradients ★ Maintenance of membrane phospholipid ★ Maintenance of skeletal protein plasticity ★ Maintenance of functional ferrous hemoglobin ★ Protection of cell proteins from oxidative denaturation ★ Initiation and maintenance of glycolysis ★ Synthesis of glutathione ★ Mediation of nucleotide salvage reactions Via the EMP, glucose is catabolized to pyruvate (e-recall ang biochem, sa glycolysis, glucose is catabolized into pyruvate) consuming two molecules of ATP per molecule of glucose and maximally generating four molecules of ATP per molecule of glucose, for a net gain of two molecules of ATP. ○ In short, in glycolysis, hindi porket ito ang source ng energy ng RBC, hindi na ito na ngangailangan ng energy ○ In order to initiate and maintain glycolysis, kailangan may energy pa rin na kumbaga fuel para maka pag produced siya ng energy ○ Kailangan niya ng 2 moles or molecules of ATP paramakapag fx siya. And in the process, glycolysis can formulate 4 moles or molecules of ATP per one molecule of glucose. So kung yung dalawang molecules ng ATP ay na consume mo para ma produce ang 4, ilan na ang neto na gain mo or net na nacatch mo. So kung 4 ang na produce pero ginamit ang dalawa, ibig sabihin dalawa yung neto mo. A net gain of two EMB is an anaerobic pathway, 90% na pinag kukuhanan ng molecules of ATP energy ay nandito. (sundan si doc sa pic. Next pg cont.) 6 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 1. The glucose, mag sstart ka dito. Is metabolized by net mo or growth mo from your glucose. Mag your glucose-6-phosphate via the enzyme m-minus 2 ka kasi dalawa ang na consume. hexokinase d. Kaya ilan ang net mo? 2 moles of ATP a. In this process nag e-expend ang ATP, nagiging e. And then pyruvate will further metabolized into ADP in the process kasi kailangan ng ATP. Kaya lactate -1 ATP, kasi kailangan ng ATP or na cconsume This is you EMB pathway, which is the major or 2. Glucose-6-phosphate will be further converted or predominant source of energy of RBCs metabolized into Fructose-6-bisphosphate via the enzyme glucose phosphate isomerase Para mas matandaan pa nandito yung mga table 3. Further metabolized into Fructose 1, 6-bisphosphate via the enzyme GLUCOSE CATABOLISM: 1ST PHASE phosphofructokinase, which transfers a certain Substrates Enzyme Products substance kaya siya kinase. a. Yung si atp, in the process will be consumed Glucose, ATP Hexokinase G6P, ADP kaya na r-reduce siya into ADP. Kaya -1 ATP ulit 4. Fructose 1, 6-bisphosphate will be converted into Now si glucose, will be metabolized into G6P via the DHAP or dihydroxyacetone phosphate as well as enzyme hexokinase glyceraldehyde 3-phosphate via the enzyme Another substrate is ATP, kasi in this reaction kailangan aldolase ma consume ang ATP para ma convert si glucose into a. The DAP will be converted into glyceraldehyde G6P. 3-phosphate via triose phosphate isomerase The ATP will be reduced into an ADP and vice versa 5. The glyceraldehyde 3-phosphate will be converted G6P Glucose- 6- phosphate F6P into 1, 3-BPG (1,3-Bisphosphoglycerate) via the isomerase enzyme glyceraldehyde 3-phosphate dehydrogenase G6P will be converted into F6P, via the enzyme Glucose- 6. Your 1, 3 BPG will then be converted into 2,3 BPG 6- phosphate isomerase via the enzyme bisphosphoglycerate mutase. Or di kaya naman 3-phosphoglycerate via F6P, ATP 6-Phosphofructokinase F1, 6-BP,ADP phosphoglycerate kinase 7. The 2,3 BPG can be converted into F6P will be metabolized to become F1, 6-BP catalyzed by 3-phosphoglycerate via bisphosphoglycerate the enzyme 6-Phosphofructokinase. phosphatase. In the process ma c-consume rin si ATP kaya minus 2 8. The conversion of 1,3-Bisphosphoglycerate to 3 ATP agad phosphoglycerate via the enzyme phosphoglycerate kinase will yield 2 moles of F1, 6-BP Fructose biphosphate DHAP, G3P ATP. Meron ka ng net diyan na ATP aldolase 9. Another your 3-phosphoglycerate will be converted or metabolize into 2-phosphoglycerate via the F1, 6-BP will be converted into either DHAP or G3P. This enzyme phosphoglyceromutase two can be interconvertible. 10. your 2-phosphoglycerate will further metabolize into But in general F1, 6-BP will be catabolized DHAP or G3P phosphoenolpyruvate (PEP) via the enzyme via the enzyme aldolase enolase. a. Does it ring a bell? This the enzyme that is inhibited by what preservative? Sodium fluoride. It’s the ENOLASE (ang “inalis” enolase na enzyme ni sodium fluoride sa glycolysis in order to preserve glucose. Because if you inhibit your enolase then hindi mag p-proceed ang glycolysis, so hindi na breakdown ang glucose. Na preserve ang glucose. ito ang mechanism ni sodium fluoride in preventing your glycolysis, so that ma preserve si glucose b. Si ENOLASE ang enzyme na “inalis” ni sodium fluoride sa glycolysis pathway to prevent glycolysis 11. phosphoenolpyruvate will be catalyzed via the pyruvate kinase a. in this case nag kakaroon ka ng ATP. b. So ilan na ang ATP? dalawa, dalawa. 2 + 2 =4 c. Unfortunately, yung 1st two kanina, si hexokinase at phosphofructokinase nag expend sila ng tig isang ATP. Kaya from the four ATP na 7 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 GLUCOSE CATABOLISM: 2nd PHASE GLUCOSE DIVERSION PATHWAYS (SHUNTS) Substrates Enzyme Products Now, kung hindi naman EMB pathway since 90%, san yung remaining 10%? na kay HEXOSE MONOPHOSPHATE PATHWAY G3P Glyceraldehyde-3-phosphate 1, 3-BPG A. HEXOSE MONOPHOSPHATE PATHWAY dehydrogenase a. Energy production via Aerobic Glycolysis (10%) b. Also known as Pentose Phosphate Shunt Now, your G3P will be catabolized into a 1, 3-BPG via the c. Ang mga RBCs kasi, syempre susceptible sila sa oxidative enzyme Glyceraldehyde-3-phosphate dehydrogenase damage, so kung susceptible sila sa oxidative damage just like pag nag occumolate ka ng peroxide 1,3- BPG, ADP Phosphoglycerate kinase 3-PG, ATP d. The HMP detoxifies accumulated peroxide, an agent that oxidizes heme iron, proteins, and lipids, Your 1,3- BPG will then be converted into 3-PG or into 2,3-BPG especially those containing thiol groups. Peroxide via the enzymes Phosphoglycerate kinase and arises spontaneously from the reduction of oxygen Biphosphoglycerate mutase, respectively in the cell's aqueous environment. By detoxifying In the process of conversion, your 1,3- BPG into 3-PG, ATP is a peroxide, the HMP extends the functional life product. Dalawa span of the RBC. e. Kumbaga tumatanda tayo kasi na expose tayo to 1,3- BPG Biphosphoglycerate mutase 2,3-BPG oxidizing agent or oxidative damages. So in order to prevent yung maagang pag tanda or pagkasira ng mga 2,3- BPG Biphosphoglycerate 3-PG cells just like RBCs, of course we have to neutralize or phosphatase prevent it from happening. And this is via hexose monophosphate pathway or shunt Your 2,3- BPG will be converted into 3-PG via f. Tinawag siyang shunt kasi its a shunt. Parang siya ay Biphosphoglycerate phosphotase shortcut kumabaga or di kaya para siyang singit or branch dito sa may glycolysis g. So your glucose will be converted into Glucose 6-phosphate via the enzyme hexokinase since nasa pentose phosphate tayo, your glucose 6-phosphate will be converted into 6-phospho-gluconate via the enzyme glucose-6-phosphate dehydrogenase so that the product of these reaction will be the reduction of nicotinamide adenine diphosphate (NADP) into Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NADPH). h. SI NADPH, ay gagamiting substrate ni glutathione reductase para yung oxidize glutathione ay ma reduce GLUCOSE CATABOLISM: 3rd PHASE into a reduced glutathione i. Itong reduced glutathione na ito ang mag pprotekta sa Substrates Enzyme Products ating mga cells. Which will be used by your glutathione reductase to reduced to to convert your peroxide into 3-PG Monophosphoglycero 2-PG water mutase j. You know that your peroxide kasi is sinisira niya or dinadamage niya yung mga cells natin. So kailangan Your 3-PG will be converted into 2-PG via the enzyme natin siyang sirain or e-reduced kaya ito rin ang one of Monophosphoglycero mutase the reason why glutathione is beeing used in cosmetics purposes para bumata (to prevent oxidative damage 2-PG Enolase PEP para young looking pa rin or kaya naman hindi madaling amg age ang ating mga cells. Yan yung glutathione na (Phosphopyruvate reduced glutathione na role niya). hydratase) k. Basta ang role ni HMP, is to protect the cells from oxidative damaged. SO if you have G6PD Your 2-PG will be converted into PEP via enzyme Enolasem other term is Phosphopyruvate hydratase deficiency, what will happen? your RBCs are prone to oxidative damage. Meaning madali PEP, ADP ADP Pyruvate kinase Pyruvate, ATP silang mamatay or ma damaged or hindi nila na f-fullfill ang 120 days lifespan nila, kung meron PEP will now be catalyzed to become a Pyruvate via the kang G6PD deficiency. Kaya nag kakaroon ng enzyme Pyruvate kinase hemolysis. ANong tawag sa hemolysis na yun? in tis process, there is 2 moles of ATP produce, a total of 4 INTRINSIC DEFECT, kasi ang G6PD is an moles of ATP per molecule of glucose BUT a net amount of 2 enzyme that is innate or natural or intrinsic part of moles of ATP because of the consumption of 2 ATP in the your RBC kinase reaction (hexokinase and phosphofructokinase) l. The HMP diverts glucose 6-phosphate (G6P) to pentose phosphate by the action of glucose-6-phosphate dehydrogenase (G6PD). In the process, oxidized nicotinamide adenine dinucleotide phosphate (NADP+) is converted to the reduced form (NADPH). NADPH is then available to reduce the oxidized form of glutathione (GSSG) to its reduced form (GSH) using 8 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 glutathione reductase. Once glutathione is B. METHEMOGLOBIN REDUCTASE PATHWAY reduced, it is available to reduce peroxide to water From you Hgb, midterms, ano ibig sabihin ng and oxygen via glutathione peroxidase. METHEMOGLOBIN? isa siyang hgb na ang kaniyang m. Reduced glutathione is made available via NADPH iron ay nasa oxidize state (ferric state) to prevent oxidative denaturation of hemoglobin. Also known as Hemiglobin n. Remember ano yung role niya? G6PD provides Unfortunately, MetHgb are not able to hold your Hgb. the only means of generating NADPH for Kaya kailangan natin siyang e-reduced. Para ma glutathione reaction, and in its absence, the reduced siya you have your METHEMOGLOBIN erythrocytes are particularly vulnerable to REDUCTASE PATHWAY oxidative damage a. Maintains the iron present in the hemoglobin molecule o. G6PD deficiency is the most common human in a functional reduced state (Fe+2) for oxygen RBC enzyme deficiency worldwide. transport p. G6PD is the most common enzyme deficiency in i. Kasi dba ferrous ang siyang nag hold dun sa O2 para the world, as well as here in the philippines. That is ma transport siya and eventually mapakawalan why G6PD is part of the newborn screening. b. Heme iron is constantly exposed to oxygen, an Kasi alam niyo na, if na eexposed kasi ito sa mga oxidizing agent. In addition, the accumulation of oxidizing agents, nag kakaroon sila ng attacts or peroxide oxidizes heme iron from the ferrous to the episode ng hemolysis. That is why may mga ferric state, forming methemoglobin bagay na iiwasan kapag ikaw isang batang may c. HMP is not able to reduce methemoglobin once it G6PD deficiency, but you will live a normal life forms. naman, may mga dapat ka lang iwasan or dapat d. NADPH is able to do so, but only slowly. The hindi ibigay para hindi ma induced yung oxidative reduction of methemoglobin by NADPH is far more damaged sa mga RBCs efficient in the presence of methemoglobin reductase, more properly called cytochrome b5 reductase (cytob5r) ★ Balikan yung diagram ng glycolysis (meron yung Methgb pathway dun) ★ Now, si hexose monophosphate pathway is not able to reduced your methgb or the ferric into a ferrous ★ Ano ba kasi role ni HMP? To prevent oxidative damage. Meron tayong ibang pathway to maintain yung iron in its reduced ferrous state, and that is your Methemoglobin reductase Glucose metabolism: HMP pathway Substrates Enzyme Products ★ Although si NADPH is able to reduced naman your Methgb into a Hemoglobin kaya lang its very slow. but don't worry because we have another pathway in order for us to reduced the ferric G6P Glucose- 6- phosphate 6-PG into a ferrous state, by way of methgb reductase dehydrogenase ★ So methemoglobin reductase ay r-reduced niya si iron into a ferrous state para ma form na ulit si hgb which is able to bind w/ Substrates here will start from G6P, saan galing O2 efficiently to distribute it to the peripheral circulation ito? from your glucose catabolized into G6P via glucokinase or hexokinase. C. RAPOPORT-LUEBERING PATHWAY Then you G6P will be catalyzed to become 6-PG a. Generates 2,3-DPG (or 2,3-BPG) which via the enzyme Glucose- 6- phosphate enhances delivery of oxygen to the tissues by dehydrogenase decreasing oxygen affinity or competing with oxygen for hemoglobin 6-PG Phosphogluconolactonase R5P i. Generates 2,3-DPG (or 2,3-BPG), does it ring a bell? or Remember yung ating Oxyhemoglobin Dissociation Phosphogluconate curve, there is shift to the left and right because or by dehydrogenase way of RAPOPORT-LUEBERING PATHWAY tumataas ang 2,3-DPG And then you 6-PG will be converted into R5P via ii. Is it shift to the left or right? Shift to the RIGHT the enzyme Phosphogluconolactonase or 1. CABET DO THE RIGHT THING Let go iii. Ano ginagawa ni 2,3-DPG? decreasing oxygen Phosphogluconate dehydrogenase affinity, kaya e-llet go niya si O2. Or makikipag compete siya kay Hgb para ma let go si O2 ni Hgb par ama distribute siya sa peripheral circulation iv. (Balikan yung diagram ng glycolysis) nandun itong pathway na ito, mag sstart siya kay 1, 3 bisphosphoglycerate to be catabolized to be 2,3-DPG via your bisphosphoglycerate mutase v. Si 2,3-DPG ay ine-enhance niya ang pag decrease ng oxygen affinity vi. So kung mataas ang 2,3-DPG mo, mababa ang O2 affinity pero ang ibig sabihin niyan ay na distribute ang O2 to the peripheral circulation so that it is shift to the right is ithe Oxyhemoglobin Dissociation curve 9 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA  BATCH SORBETES ‘25 10 | LIM, JULIANA NICOLE B. │TORRES, ANGELICA