number Done by Corrected by Doctor Nafeth Abu Tarbosh

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1 number 1 Dne by Crrected by Dctr Nafeth Abu Tarbsh 1 P a g e

Abut this Curse: In this curse, we will study structure-functin relatinship, plasma prteins and energy metablism with dr Nafith, carbs metablism (frm carbs t energy) with dr Nayef, lipid metablism

2 Abut this Curse: In this curse, we will study structure-functin relatinship, plasma prteins and energy metablism with dr Nafith, carbs metablism (frm carbs t energy) with dr Nayef, lipid metablism (frm fatty acids t energy) with dr Faisal, and then prtein and nucleic acid metablism with dr Diala, and finally besity, vitamins, nutritin and ther cmmn tpics in metablic prcesses with dr. Nafith A brief intrductin: Here yu can find Dr. Nafith s slides: Generally, Fd cnversin will prduce acetyl CA at the end.all macrmlecules wuld becme a cmmn mlecule, this cmmn mlecule is called Acetyl CA. Carbs, Lipids, Prteins and Nucleic Acids will cnvert t acetyl CA. Let s take Carbs as an example, Carbhydrates can be brken dwn t glucse, glucse t pyruvate and then pyruvate will turn t acetyl CA. Acetyl CA will g t Krebs cycle, this is called energy metablism, and energy metablism is cmmn t all macrmlecules. Krebs cycle has tw ther names Bld: a- Citric acid cycle b- Tricarbxylic Acid cycle Let s start: In the first tw lectures, we are suppsed t answer the fllwing questins: What is plasma, and hw can we extract it? What are the different cmpnents f plasma? Plasma prteins (general functins, basis f classificatin, assciated prcesses and mlecules) Plasma prteins (structure, synthesis, functin & diseases assciated) 2 P a g e

Bld cmpnents: - Bld cmpnents are plasma and cells : Plasma frms 55% f the bld vlume Cellular cmpnents (RBC,WBC and platelets) frm 45% f bld vlume WBC (white bld cells), als called leukcytes:

3 Bld cmpnents: - Bld cmpnents are plasma and cells : Plasma frms 55% f the bld vlume Cellular cmpnents (RBC,WBC and platelets) frm 45% f bld vlume WBC (white bld cells), als called leukcytes: Granulcytes: Neutrphils, Esinphils and Basphils Agranulcytes : Lymphcytes andmncytes The previus underlined examples were nt mentined by Dr. Nafith, but they are fund in the slides. RBC (red bld cells), als called erythrcytes Platelets when the bld is separated by its cmpnents in a test-tube, the cmpnents,frm the bttm f the tube t the tp f it, wuld be: RBCs - bttm WBCs and Platelets Plasma (the liquid, nn cellular part) the upper part. Extractin But hw culd we extract the plasma frm the bld? By Centrifugatin Mre imprtantly, by Purificatin (ESR: Erythrcyte Sedimentatin Rate) By tw techniques, we can extract plasma prteins: Salting ut: Prteins are water sluble, when adding salt (ammnium sulfate fr example), prtein slubility will decrease until it precipitates, the mre sluble the prtein is, the higher the cncentratin we need t extract the prtein. By this technique, we can extract : fibringen, albumin, and glbulins Electrphresis ( gel electrphresis): In this technique, we cannt use plasma directly, because f fibringen, when fibringen is expsed t air, it turns directly int fibrin,this is why cutting yur finger, 3 P a g e

4 leads t clt frmatin ( fibringen is a cltting factr). Instead f plasma, we can use serum which is a defibrinated plasma. (t make it easier, serum = plasma fibringen) When we bring a bld sample, and leave it apprximately fr an hur, the cellular cmpnents will start t precipitate, but it is imprtant t say that this prcess may take either mre r less than an hur in sme pathlgical cases (diseases) r physilgical prcess. The ESR was previusly mre cmmn, when it is fast, it can indicate certain diseases and physilgical prcesses (such as pregnancy), but when it takes lnger time, it can be an indicatr t ther diseases and physilgical prcesses, but nw we can use direct, specific tests fr certain diseases r physilgical prcesses Mre details abut electrphresis when putting plasma prteins in the gel, they wuld mve frm negative electrde t psitive electrde, albumin is the fastest (this is why it has the highest negative charges), then a grup f glbulin prteins (alpha, beta, gamma) cmes next. Nte:Albumin is smaller than glbulin, and slightly negatively charged resulting bands: Albumin (ne large band) Glbulins (3 main bands): α band: - this band separates int tw bands, Glbulin Alpha1 and Glbulin Alpha2, they were bth called alpha because they are clse t each ther in mlecular weight. It is imprtant t knw that Alpha1 is nt a single prtein, it is a grup f prteins & Alpha2 is a grup f prteins, t. 1. α1 regin cnsists mstly f α1-antitrypsin 2. α2 regin is mstly haptglbin, α2-macrglbulin, & cerulplasmin β band: Beta prteins are als a grup f prteins, and if they were given enugh time, they might separate int Beta1 and Beta2. (transferrin, LDL, cmplement system prteins) γ band: the immun-glbulins Gamma Glbulins- are antibdies, immunglbulins (IgG, IgD, IgE, IgM and IgA) By this technique (electrphresis), we usually get five bands which are (albumin, glbulin α1, glbulin α2,glbulin β, and glbulin γ) -frm the least mlecular weight t the mst- 4 P a g e

5 Plasma Its definitin (liquid part f the bld where cells are suspended, it is cmpsed f 92% water and 8% slids -plasma prteins in particular-) What can we find in plasma? We can find everything (except cellular cmpnents), such as: Gases, wastes (such as nitrgenus wastes), Amin acids, Electrlytes, ins, prteins (albumin, glbulin and fibringen), enzymes, hrmnes, Nutrients, Ketne bdies, Carbs as mnsaccharides, fatty acids, nucletides and many ther stuff,it is simply a reflectin f the persn We can put Everything int tw main grups: Organic Plasma prteins: Albumin, Glbulins & Fibringen Nn-prtein nitrgenus cmpunds: urea, free amin acids, uric acid, creatinine, creatine & NH3 Lipids: Chlesterl, TG, phsphlipids, free fatty acids Carbhydrates: Glucse, fructse, pentse Other substances such as: Ketne bdies, bile pigments, vitamins, enzymes & hrmnes Inrganic: Na+,K+,Ca2+,Mg2+,Cl-,HCO3-,HPO42-, SO42 Plasma Prteins We are gnna study, the fllwing six majr grups in plasma: Albumin & pre-albumin α1-antitrypsin Haptglbin(Hp) α1-fetprtein (AFP) Cerulplasmin C-Reacrive Prtein - But 500 plasma prteins have been identified, sme are nt detectable in healthy peple, but culd rise and becme detectable in certain diseases The nrmal range f plasma prteins 6-8 grams/ deciliters (Remember : a deciliter = 100 milliliter / a deciliter= 10^-1 liter) General prperties All plasma prteins can be synthesized in liverexcept gamma glbulin, gamma glbulins are synthesized in B cells /plasma cells; lymph ndes, bne marrw, spleen) Mst plasma prteins are synthesized as preprteins (signal peptide), meaning plasma prteins in liver are inactive, because they wn t wrk there, what happens is that a single peptide gets ut f liver cells and then t bld where it becmes active, this is a prperty that all plasma prteins synthesized in liver share, (preprteins need t underg psttranslatinal mdificatins t becme activeby 5 P a g e

6 adding a mleculein a prcess called glycsylatin r phsphlyratin, ther mdificatins areprtelysisr breaking the prtein t becme fully functinal(such as albumin) Sme plasma prteins need shrt time t mve frm liver cells t bld, thers need mre time and this is called transit time. Simple & cnjugated prteins (glycprteins & lipprteins) Mst plasma prteins attached t carbs, in ther wrds, Mst plasma prteins are Glycprteins (N- r Olinked). Albumin is the majr exceptin, and this has a clinical significance, because if albumin was bund t a carb mlecule, this wuld increase bld s viscsity/ thickness (which makes it harder t mve), because albumin is already negatively charged and carbhydrates add t its negativity and it is the mre abundant plasma prtein. Plasma prteins have different half lives, it culd be determined thrugh istpe labeling studies (I 131 ) by injecting the persn with a prtein f interst, which is radilabelled (flurescence fr example) t be easily traced, and then a sample is taken t see hw much is left Albumin has a half life f 20 days haptglbin has half life f 5 days ( if nt bund ) This half life f prteins might be affected by many factrs, I. Diseases can affect half-lives (ex. Crhn s disease), albumin may be reduced (1 day) II. Prtein-lsing gastrenterpathy, if smene had a prblem with intestines, and the bld which mves near intestines leak sme plasma t intestines, the cncentratin f a prtein wuld decrease dramatically Prtein-lsing gastrenterpathy: characterized by an excessive lss f serum prteins int the gastrintestinal tract Many mlecules shw electrphretic and iselectric fcusing mbility. Many plasma prteins exhibit plymrphism. Plymrphism is a Mendelian (mngenic) trait that exists in the ppulatin in at least tw phentypes- neither f which is rare, (The ABO bld grups are the best-knwn examples). Plasma prteins shwing plymrphism are α1-antitrypsin, haptglbin, transferring, cerulplasmin, and immunglbulin - Questin: Why Hemglbin is nt a Plasma Prtein? Answer: Because it is inside RBC, it is frm the cellular cmpnents, it is nt cnsidered as plasma prtein. (Hemglbin mlecular weight is 65 kil Daltn) Plasma Prteins and Plymrphism Mutatins can ccur t any gene in any prtein, these mutatins can either be harmful (causing a disease) r harmless (clr f eyes r hair ), these mutatins can lead t plymrphisms, but Hw?if mre than 1% f ppulatin gt this genetic mutatin, it wuld be called plymrph, the 6 P a g e

7 prtein wuld be said t have tw frms (e.g. 2% and 98%)Plymrphism, when a specific site n a chrmsme has multiple alleles in the ppulatin, it is said t be plymrphic (many frms) Structure-functin relatinship Albumin Mlecular Weight = 69 kil Daltn (it is ellipsidal in shape) Fibringen (sluble, elngated) when yu gt an injury, fibringen turns t fibrin, and fibrin is insluble, and this what leads t bld clt Structure-Functin relatinship significance: (shape has a great effect n functin) If albumin s structure was elngated like fibringen, the human will nt live. Applicatins: Densitmeter: a device that measures the density f each band and presents it in peaks albumin has the highest cncentratin -highest peak- f all plasma prteins in any bld sample 50-60% f plasma prteins, then its nrmal cncentratin wuld be apprximately ( ), dn t memrize the relative values f the glbulins but ntice that their cncentratins are clse t each ther, refer t the slides t see the values. Clinically, Yu cannt diagnse smene with albumin deficiency unless their albumin cncentratin was less than 2, this cnditin is called hypalbuminemia. Hematcrit (packed cell vlume PCV) is the cells vlume ver the whle bld vlume, if a persn has a hematcrit f 40, this means that 40 percent f the bld vlume is cells and the remainder is plasma, let s have a simple exercise, if the hematcrit is 0.4 (40%) and the ttal bld vlume is 5 liters, calculate the plasma vlume Answer: hematcrit= cells vlume/ ttal bld vlume 0.4 = cells vlume/5 Cells vlume= 2 Ttal bld vlume = cells vlume + plasma vlume Then plasma vlume equals 3 liters Extra Nte: when yu g t sme references yu might see this test called packed red bld cell vlume, because f the fact that RBCs frm the largest prtin f the cellular cmpnent. 7 P a g e

In adult males, the measured hematcrit is abut 47% and in adult females is abut 42% D yu remember when we said that plasma frms 55% f the bld vlume and cells frm 45% f bld vlume, but actually it is

A is nrmal B( chrnic/ acute) infectin, inflammatin r cancer cases - Explanatin: frm the first glance, yu might think that it is an indicatin fkidney failure because albumin has lw cncentratin cmpared

8 In adult males, the measured hematcrit is abut 47% and in adult females is abut 42% D yu remember when we said that plasma frms 55% f the bld vlume and cells frm 45% f bld vlume, but actually it is nt the same in males and females accrding t thehematcritsmentined abve! A is nrmal B( chrnic/ acute) infectin, inflammatin r cancer cases - Explanatin: frm the first glance, yu might think that it is an indicatin fkidney failure because albumin has lw cncentratin cmpared t thers, but if it was a kidney failure, all prteins shuld be at lw cncentratin. - (Relatively, this case is ne ut f tw ptins, either the albumin is lwer in cncentratin than gamma glbulin r albumin is equal t gamma in cncentratin. In ther wrds, the glbulins are either slightly higher r unchanged, Einstein can help in Bichemistry, t) Albumin is nt an acute phase prtein we will talk abut this piece f infrmatin in mre details in the fllwing lecture. 8 P a g e

9 Cliver prblems, such as hepatitis Explanatin: all plasma prteins synthesized in liver except immunglbulins (gamma glbulins), s it is a liver prblem, because all prteins are relatively lw in cncentratin except gamma glbulins, they are synthesized in beta cells. D kidney failure (nephrtic syndrme) All prteins cncentratins are lw Clinical Nte: nrmally, there shuld be n prteins in urine, (in sme cases, slight amunt culd be neglected thugh) If Yu Want t G Fast, G Alne. If Yu Want t G Far, G Tgether - A message t Dctr P a g e

Anemia. There are three types of Anemia that effect EB patients. They are Iron Deficiency, Chronic Inflammatory and Nutritional.

Anemia. There are three types of Anemia that effect EB patients. They are Iron Deficiency, Chronic Inflammatory and Nutritional. Anemia Mst patients with Recessive Dystrphic Epidermlysis Bullsa are als Anemic. Anemia in EB is caused by many factrs and can becme very severe if nt treated. Anemia means nt having enugh red cells and