General Biochemistry: Amino Acids and Proteins PDF

General Biochemistry (19068) Part 3. Amino Acids and Proteins DR. FAWZI AL-RAZEM Associate Professor of Biochemistry and Molecular Biology College of Medicine and Health Sciences, PALESTINE POLYTECHNIC UNIVERSITY P.O.BOX 198...

General Biochemistry (19068) Part 3. Amino Acids and Proteins DR. FAWZI AL-RAZEM Associate Professor of Biochemistry and Molecular Biology College of Medicine and Health Sciences, PALESTINE POLYTECHNIC UNIVERSITY P.O.BOX 198 HEBRON, PALESTINE PHONE: +972-2-223-1921 EXT. 9915 FAX: +972-2-223-5505 E-MAIL: [email protected] Mondays + Wednesdays: 8:00 - 9:15 (group 1) Mondays + Wednesdays: 11:00 - 12:15 (group 2) Mondays + Wednesdays: 2:00 - 3:15 (group 3) General Bi ochemi st ry 3/4/2025 1 CHAPTER OUTLINE I. GENERAL STRUCTURE OF THE AMINO ACIDS II. CLASSIFICATION OF AMINO ACID SIDE CHAINS A. Nonpolar, aliphatic amino acids B. Aromatic amino acids C. Aliphatic, polar, uncharged amino acids D. Sulfur-containing amino acids E. The acidic and basic amino acids III. VARIATIONS IN PRIMARY STRUCTURE A. Polymorphism in protein structure B. Tissue and developmental variations in protein structure 1. Developmental variation 2. Tissue-specific isoforms C. Species variations in the primary structure of insulin IV. MODIFIED AMINO ACIDS A. Glycosylation B. Fatty acylation or prenylation C. Regulatory modifications D. Other amino acid posttranslational modifications E. Selenocysteine 3/4/2025 2  KEY POINTS  A protein’s unique characteristics including its three-dimensional folded structure are dictated by its linear sequence of amino acids, termed its primary structure.  The primary structures of all of the diverse human proteins are synthesized from 20 amino acids arranged in a linear sequence determined by the genetic code.  Each three base (nucleotide) sequence within the coding region of a gene (the genetic code) specifies which amino acid should be present in a protein. The genetic code is discussed further later on in the course.  All amino acids contain a central α-carbon, joined to a carboxylic acid group, an amino group, a hydrogen, and a side chain, which varies between the 20 different amino acids.  At physiological pH, the amino acids are zwitterions; the amino group is positively charged, and the carboxylate is negatively charged.  In proteins, amino acids are joined into linear polymers called polypeptide chains via peptide bonds, which are formed between the carboxylic acid of one amino acid and the amino group of the next amino acid.  Amino acid side chains can be classified either by polarity (charged, nonpolar hydrophobic, or uncharged polar) or structural features (aliphatic, cyclic, or aromatic).  Depending on their side chain characteristics, certain amino acids cluster together to exclude water (hydrophobic effect), whereas others participate in hydrogen bonding. Cysteine can form disulfide bonds, whereas charged amino acids can form ionic bonds.  Amino acids in proteins can be modified by phosphorylation, carboxylation, or other reactions after the protein is synthesized (posttranslational modifications).  Alterations in the genetic code may lead to mutations in the protein’s primary structure, which can affect the protein’s function.  Proteins with the same function but different primary structure (isoforms and isozymes) can exist in different tissues or during different phases of development. 3/4/2025 3 I. GENERAL STRUCTURE OF THE AMINO ACIDS - 20 common α-amino acids found in proteins. - α-carbon has H atom and a side chain (-R). The -R is different for each amino acid. Positively Charged (Basic) Amino Acids: Lysine (K) Arginine (R) Histidine (H) Negatively Charged (Acidic) Amino Acids: Aspartic Acid (D) Glutamic Acid (E) FIGURE 1. Amino acid structure. A. General structure of the amino acids found in proteins. The carbon contains four substituents; an amino group, a carboxyl group, a hydrogen atom, and a side chain (R). Both the amino and carboxyl groups carry a charge at physiological pH. B. Dissociation of the α-carboxyl and α-amino groups of amino acids. At physiological pH (7), a form in which both the α-carboxyl and α-amino groups are charged 3/4/2025 predominates. Some amino acids also have ionizable groups on their side chains 4 - All amino acids but glycine, the α-carbon is an asymmetric carbon atom that has four different substituents and can exist in either the D or L configuration. - The sequence of amino acids, termed the primary structure, is determined by the genetic code for the protein. FIGURE 2. Peptide bonds. Amino acids in a polypeptide chain are joined through peptide bonds between the carboxyl group of one amino acid and the amino group of the next amino acid in the 3/4/2025 sequence. L-configuration is the biologically active 5  Review Question-1 All of the amino acids that are used to synthesize human proteins (with the exception of glycine) have which one of the following in common? A. An aromatic group B. A hydroxyl group C. An asymmetric carbon in the D-configuration D. An asymmetric carbon in the L-configuration E. An asymmetric β-carbon 3/4/2025 6 I. CLASSIFICATION OF AMINO ACID SIDE CHAINS FIGURE 3. The side chains of the amino acids. The side chains are highlighted. The amino acids are grouped by the polarity and structural features of their side chains. These groupings are not absolute, however. Tyrosine and tryptophan, often listed with the nonpolar amino acids, are more polar than other aromatic amino acids because of their phenolic and indole rings, respectively. The single- and three-letter codes are also indicated for each amino acid. 3/4/2025 7  Review Question-2 A protein loses activity with a V96L mutation. Activity can be restored to the protein by introducing a second mutation, V172A. The most likely possible explanation for this finding is which one of the following? A. Substitution of one hydrophilic residue for another restores activity B. The V96L mutation disrupts an ionic interaction stabilizing the protein structure, whereas the V172A mutation allows restoration of the ionic interaction C. The V96L mutation disrupted hydrogen bond stabilization of the structure, whereas the V172A mutation allowed restoration of the hydrogen bond interactions D. The V96L mutation introduced steric hindrance into the structure, whereas the V172A relieved the steric hindrance introduced by the first mutation E. The V96L mutation disrupted a disulfide bond, whereas introducing the V172A mutation allowed the disulfide bond to re-form 3/4/2025 8 A. Nonpolar, Aliphatic Amino Acids - Glycine is the simplest amino acid. - Alanine and the branched chain amino acids (valine, leucine, and isoleucine) have bulky, nonpolar, aliphatic (open-chain hydrocarbon) side chains and exhibit a high degree of hydrophobicity. B. Aromatic Amino Acids - Contain ring structures with similar properties, but their polarity differs a great deal. - The aromatic ring is a six-member carbon-hydrogen ring with three conjugated double bonds (the benzene ring or phenyl group). These hydrogen atoms do not participate in hydrogen bonding. 3/4/2025 9  Review Question-3 Proteins, which are composed of amino acids, help transport lipids in the bloodstream. These proteins need to be able to cluster with other nonpolar molecules and exclude water. Which of the following would best describe the side chains of these amino acids in the lipid transport proteins? A. A more positive hydropathic index B. A more negative hydropathic index C. A neutral hydropathic index D. A pKa of the primary carboxylic acid group of approximately 2 E. A pKa of the α-amino group of approximately 9.5 3/4/2025 10 C. Aliphatic, Polar, Uncharged Amino Acids - Amino acids with side chains that contain an amide group (asparagine and glutamine) or a hydroxyl group (serine and threonine) can be classified as aliphatic, polar, uncharged amino acids. - Asparagine and glutamine are amides of the amino acids aspartate and glutamate. D. Sulfur-containing Amino Acids - Both cysteine and methionine contain sulfur. The side chain of cysteine contains a sulfhydryl group that has a pKa of about 8.4 for dissociation of its hydrogen, so cysteine is predominantly undissociated and uncharged at the physiological pH of 7.4. 3/4/2025 11 - Cystine, is present in blood and tissues, and is not very water-soluble. - In proteins, the formation of a cystine disulfide bond between two appropriately positioned cysteine sulfhydryl groups often plays an important role in holding two polypeptide chains or two different regions of a chain together. FIGURE 4. A disulfide bond. Covalent disulfide bonds may be formed between two molecules of cysteine or between two cysteine residues in a protein. The disulfide compound is called cystine. The hydrogens of the cysteine sulfhydryl groups are removed during oxidation. 3/4/2025 12  Review Question-4 One of the main sources of nonvolatile acid in the body is sulfuric acid generated from the sulfur-containing compounds in ingested food or from the metabolism of the sulfur- containing amino acids. Which of the following amino acids would lead to sulfuric acid formation? A. Cysteine and isoleucine B. Cysteine and alanine C. Cysteine and methionine D. Methionine and isoleucine E. Isoleucine and alanine 3/4/2025 13  Review Question-5 The following Questions refer to the following patient: A patient with recurrent kidney stones is found to have an inherited amino acid substitution in a transport protein that reabsorbs certain amino acids from the glomerular filtrate so they are not lost in the urine. 1. Which of the following amino acid groups are not reabsorbed from the glomerular filtrate in this disease process? A. Cysteine, methionine, and arginine B. Cysteine, methionine, and lysine C. Cysteine, arginine, and lysine,Ornithine D. Methionine, arginine, and lysine Cystinuria E. Methionine, arginine, and histidine 2. Which one of the following amino acids is most responsible for this patient’s recurrent kidney stones? A. Cysteine B. Methionine C. Arginine D. Lysine E. 3/4/2025 Histidine 14 E. The Acidic and Basic Amino Acids - Aspartate and glutamate have a –Ve 7.4charge ~ carboxylic acid at physiological pH. - The basic amino acids histidine, lysine, and arginine have side chains containing nitrogen that can be protonated and positively charged at physiological and { lower pH values. FIGURE 5. Electrostatic interaction between the positively charged side chain of lysine and the negatively charged side chain of aspartate. 3/4/2025 15  - The charge on these amino acids at physiological pH is a function of their pKas for dissociation of protons from the α- carboxylic acid groups, the α-amino groups, and the side chains. ‫اﻟﻮﺳﻂ‬ ‫اﻟﻮﺳﻂ‬ ‫اﻟﻮﺳﻂ‬ FIGURE 6. Titration curve of histidine. The ionic species that predominates in each region is shown below the graph. pI is the isoelectric point (the pH at which there is no net charge on 3/4/2025 the molecule). 16 https://youtube.com/shorts/5sHe_qvFs_s?si=MNcTHNCR8I2AozfN  Review Question-6 An enzyme has an aspartic acid side chain, which is critical for enzyme activity. The pH optimum of the enzyme is 5.5, and studies have shown that at pH 5.5 this critical aspartic acid side chain is in its protonated state. This can occur due to which one of the following? A. The aspartic acid side chain is in a hydrophobic environment within the protein. B. The aspartic acid side chain is surrounded by K and R amino acid side chains. C. The pKa for this aspartic acid side chain is reduced by the structure of the enzyme. D. The aspartic acid side chain is stabilized by ionic interactions within the protein. E. The aspartic acid side chain is involved in hydrogen bond formation with L and V side chains. 3/4/2025 17  in sickle cell anemia, glutamic replaced with valine in #6 II. VARIATIONS IN PRIMARY STRUCTURE - The primary structure of a protein can vary to some degree between species. Embryos and fetuses use HbF (fetal hemoglobin) because it has a higher oxygen affinity than adult hemoglobin (HbA). This helps the developing baby efficiently extract oxygen from the mother’s blood. A. Polymorphism in Protein Structure Why Does the Fetus Use HbF? 1. Higher Oxygen Affinity: HbF binds oxygen more tightly than HbA, allowing the fetus to absorb oxygen even when - The variations generally arise from mutations in DNA that are maternal oxygen levels are lower. This is essential because the fetus relies entirely on oxygen from the placenta. passed to the next generation. 2. Different Globin Composition: HbF is made of two alpha (α) and two gamma (γ) globin chains instead of the beta (β) chains - The mutations can result from the substitution of one base for found in adult hemoglobin. The gamma chains reduce binding to 2,3-BPG, a molecule that lowers oxygen affinity in adult hemoglobin, allowing HbF to “steal” oxygen from maternal HbA. another in the DNA sequence of nucleotides (a point mutation), 3. Smooth Transition at Birth: After birth, the baby’s lungs take over oxygen exchange. from deletion or insertions of bases into DNA, or from larger Over the first few months of life, HbF is gradually replaced by HbA as the oxygen environment changes. changes. This switch from HbF to HbA ensures the baby adapts properly to breathing outside the womb. 3/4/2025 18  ‫ﺣﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء )‪ & (RBCs‬﮳ﻌﻤﺮ اﻟ< ﮳=>& ﮴< ﮵ﻨﺎت اﻟﱵ & ﮴ﺤﺘ‪ DC‬﮵ﻬﺎ‪ ،‬و ﮲‬ ‫ﺣﺎﺻﺔ‬ ‫& ﮲ﻌﻢ‪ & ،‬﮵ﺘﺤﺪد ﻋﻤﺮ ﮲‬ ‫اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ واﻟ< ﮳=>& ﮴< ﮵ﻨﺎت اﻟ‪K‬ﻌﺸﺎ& ٔ< ﮵ﺔ‪.‬‬ ‫ﺣﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء & ﮳ﺎﻟ< ﮳=>& ﮴< ﮵ﻨﺎت؟‬ ‫ﻟﻤﺎذا & ﮵ﺘﺤﺪد ﻋﻤﺮ ﮲‬ ‫‪In Class Discussion-1‬‬ ‫‪.1‬﮲ﻋ& ﮴< ﮵ﻨﺎت ﮳‬ ‫ﺤﺎع اﻟﻌ﮲ﻄﻢ‪.‬‬ ‫ﺣﻮدة ﻣﻨﺬ & ﮴ﻜ‪ &C‬﮵ﻨﻬﺎ ‪j K h‬‬ ‫‪& i‬﮲ ﮲‬ ‫ﺤﻌﻠﻬﺎ & ﮴ﻌﺘﻤﺪ ﻋﲆ اﻟ< ﮳=>& ﮴< ﮵ﻨﺎت اﻟﻤﻮ ﮳‬ ‫ ﻫﺬا & ﮵ ﮳‬ ‫‪Will is a 17-year-old boy who presented to the hospital emergency department with‬‬ ‫‪o‬‬ ‫‪ &.2‬﮴ﻠﻒ اﻟ< ﮳=>& ﮴< ﮵ﻨﺎت ﻣﻊ ﻣ=>ر اﻟﻮ‪n‬ﺖ‪:‬‬ ‫ﺤﻠ< ﮵ﺔ‪rq ،‬ﻌﺮض اﻟ< ﮳=>& ﮴< ﮵ﻨﺎت ﻣ‪t‬ﻞ اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ واﻟ< ﮳=>& ﮴< ﮵ﻨﺎت اﻟ‪K‬ﻌﺸﺎ& ٔ< ﮵ﺔ ﻟﻸﻛﺴﺪة‬ ‫ ﻣﻊ & ﮴‪co‬ﺪم ﻋﻤﺮ اﻟ ﮲‬ ‫‪severe pain in his lower back, abdomen, and legs, which began after a 2-day history of‬‬ ‫واﻟ‪r‬ﻠﻒ‪.‬‬ ‫‪nausea and vomiting caused by gastroenteritis. He was diagnosed as having sickle cell‬‬ ‫ﺤﻼ&ﺎ﮵ أ‪o n‬ﻞ ‪o n‬ﺪرة ﻋﲆ اﻟﻤ=>ر ﻋ< ﮳ﺮ اﻷوﻋ< ﮵ﺔ اﻟﺪﻣ‪ &C‬﮵ﺔ‬ ‫ﺤﻌﻞ اﻟ ﮲‬ ‫ & ﮵ﺆدي ذﻟﻚ إﻟﻰ ‪conK‬ﺪان اﻟﻤ=>& ﮲ﺔ‪ ،‬ﻣﻤﺎ & ﮵ ﮳‬ ‫اﻟﺪ‪ ،‬﮳ﻌﺪﻫﺎ & ﮵ﺘﻢ & ﮴ﺪﻣ< ﮵ﺮﻫﺎ ‪j K h‬‬ ‫ﺣﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء ﺣﻮا~ ‪j‬‬ ‫ & ﮵< ﮳ﻠﻎ ﻣﺘﻮﺳﻂ ﻋﻤﺮ ﮲‬ ‫‪similar vaso-occlusive sickle cell crises. Sickle cell anemia is caused by a mutation of DNA‬‬ ‫ﺤﻼ&ﺎ﮵ اﻟ< ﮳ﻠﻌﻤ< ﮵ﺔ‪.‬‬ ‫& ﮳ﻮاﺳﻄﺔ اﻟ ﮲‬ ‫ﺣﺪ& ﮵ﺪة‪.‬‬ ‫ﺣﻼ&ﺎ﮵ ﮳‬ ‫‪ & i‬﮴ﻜ‪ &C‬﮵ﻦ ﮲‬ ‫‪K‬‬ ‫ﺤﺪاﻣﻬﺎ ‪j h‬‬ ‫ & ﮵ﺘﻢ إﻋﺎدة & ﮴ﺪ>& ﮵ﺮ ﻣﻜ‪ &C‬﮲ﺎ‪ D‬﮴ﻬﺎ‪ ،‬ﻣ‪t‬ﻞ اﻟﺤﺪ& ﮵ﺪ ﻣﻦ اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ‪ ،‬ﻻﺳﺘ ﮲‬ ‫‪that changes just one amino acid in the hemoglobin β chains from a glutamic acid to a‬‬ ‫‪valine. Hemoglobin is the protein present in red blood cells that reversibly binds oxygen‬‬ ‫ﺤﻼ&ﺎ﮵ ؟‬ ‫ﻣﺎ اﻟﺬي & ﮵ﺤﺪد & ﮴ﻠﻒ اﻟ ﮲‬ ‫ﺤﻠ‪C‬ي‪.‬‬ ‫﮵‬ ‫﮳‬ ‫﮲‬ ‫﮵‬ ‫ اﻷﻛﺴﺪة‪ & :‬﮴‪ &€‬﮶ﺮ ﻋﲆ اﻟﻬ& ﮴< ﮵ﻨﺎ‪ D‬﮴ﻬﺎ ﺳﻠ< ﮵ﻤﺔ‬ ‫ﻟﺬﻟﻚ‪ & ،‬﮵ﻤﻜﻦ اﻟ‪ co‬ﻮل إن ﻋﻤﺮ ﮲‬ ‫و‪o n‬ﺪ[‪ D‬﮴ﻬﺎ ﻋﲆ اﻟﻌﻤﻞ & ﮳ﻜ‪cK‬ﺎءة‪.‬‬ ‫‪cell volume (the percentage of the total volume of blood made up by red blood cells) was‬‬ ‫‪ i‬اﻟﻤﺮارة‪ ُ &> ،‬﮴ﻌﺮف ﻫﺬه اﻟﺤﺼﻮات & ﮳ﺎﺳﻢ اﻟﺤﺼﻮات اﻟﺼ< ﮳‪K‬ﻌ< ﮵ﺔ )‪.(Pigment Stones‬‬ ‫& ﮲ﻌﻢ‪ ،‬اﻟ< ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻦ & ﮵ﻤﻜﻦ أن & ﮵ﺴ< ﮳ﺐ ﺣﺼﻮات ‪j K h‬‬ ‫‪23.4% (reference range, 41% to 53%). His serum total bilirubin level (a pigment derived‬‬ ‫ﻛ< ﮵ﻒ & ﮵ﺴ< ﮳ﺐ اﻟ< ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻦ ﺣﺼﻮات ‪j K h‬‬ ‫‪ i‬اﻟﻤﺮارة؟‬ ‫‪from hemoglobin degradation) was 2.3 mg/dL (reference range, 0.2 to 1.0 mg/dL). A‬‬ ‫‪ i‬اﻟ< ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻦ ‪j K h‬‬ ‫‪ i‬اﻟﺼ‪cK‬ﺮاء‪nK ،‬ﺈ& ﮲ﻪ & ﮵ﻤﻜﻦ أن & ﮵ﺘﺤﺪ ﻣﻊ اﻟﲀﻟﺴ< ﮵ﻮم‬ ‫ﺣﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء اﻟ‪r‬ﺎﻟ‪cK‬ﺔ‪.‬ﻋﻨﺪﻣﺎ & ﮵ﻜ ‪C‬ن ﻫﻨﺎك ‘&ﺎ﮵ دة ﮲ﻋ< ﮵ﺮ ﻃ< ﮳< ﮵ﻌ< ﮵ﺔ ‪j K h‬‬ ‫اﻟ< ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻦ ﻫﻮ & ﮲ﺎ‪ D‬﮴ﺞ ﻋﻦ & ﮴ﺤﻠﻞ اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ ﻣﻦ ﮲‬ ‫‪ i‬اﻟﻤﺮارة‪.‬‬‫ﻟ< ﮵ﺸ ﻞ ﺣﺼﻮات & ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻨ< ﮵ﺔ ‪j K h‬‬ ‫‪radiograph of his abdomen showed radiopaque stones in his gallbladder. With chronic‬‬ ‫أ& ﮲ﻮاع ﺣﺼﻮات اﻟﻤﺮارة اﻟﻤ=& ﮴< ﮳ﻄﺔ & ﮳ﺎﻟ< ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻦ‪:‬‬ ‫‪.1‬اﻟﺤﺼﻮات اﻟﺼ< ﮳‪K‬ﻌ< ﮵ﺔ اﻟﺴﻮداء‪:‬‬ ‫‪hemolysis (red blood cell destruction), the amount of heme degraded to bilirubin is‬‬ ‫ﺤﻠ< ﮵ﺔ أو اﻟ‪t‬ﻼﺳ< ﮵ﻤ& ﮳< ﮵ﻨﺎت اﻟﲀﻟﺴ< ﮵ﻮم‪ ،‬اﻟﻜﻮﻟ< ﮵ﺴﺘ= ول‪ &> ،‬﮳=>& ﮴< ﮵ﻨﺎت‪.‬‬ ‫‪ i‬اﻟ‪co‬ﻨﻮات اﻟﺼ‪cK‬ﺮا>& ﮵ﺔ أو رﻛﻮد اﻟﺼ‪cK‬ﺮاء‪.‬‬ ‫ ﮲ﻋﺎﻟ< ً﮳ﺎ ﻣﺎ ‪q‬ﺘﺸ ﻞ & ﮳ﺴ< ﮳ﺐ اﻟﻌﺪ>ى اﻟﻤﺰﻣﻨﺔ ‪j K h‬‬ ‫‪bilirubin from the liver into the bile leading to bilirubinate crystal deposition in the‬‬ ‫أﺳ< ﮳ﺎب ‘&ﺎ﮵ دة اﻟ< ﮳< ﮵ﻠ< ﮵=>& ﮳< ﮵ﻦ >& ﮴ﻜ ّﻮن ﺣﺼﻮات اﻟﻤﺮارة‪:‬‬ ‫ﺣﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء(‪.‬‬ ‫‪ i‬اﻟﻤﺰﻣﻦ )‘&ﺎ﮵ دة & ﮴ﻜﺴ< ﮵ﺮ ﮲‬ ‫ ‪conK‬ﺮ اﻟﺪم اﻻ& ﮲ﺤﻼ~ ‪j‬‬ ‫‪gallbladder lumen.‬‬ ‫ أﻣﺮاض اﻟﻜ< ﮳ﺪ )ﻣ‪t‬ﻞ & ﮴ﻠ< ﮵ﻒ اﻟﻜ< ﮳ﺪ أو اﻟﺘﻬﺎب اﻟﻜ< ﮳ﺪ(‪.‬‬ ‫ اﻟﺘﻬﺎ& ﮳ﺎت اﻟ‪co‬ﻨﺎة اﻟﺼ‪cK‬ﺮا>& ﮵ﺔ‪.‬‬ ‫ اﻟﺮﻛﻮد اﻟﺼ‪cK‬ﺮا>ي )ﺿﻌﻒ & ﮴ﺪ‪nK‬ﻖ اﻟﻌﺼﺎرة اﻟﺼ‪cK‬ﺮا>& ﮵ﺔ(‪.‬‬ ‫‪3/4/2025‬‬ ‫‪19‬‬ ‫اﻷﻋﺮاض‪:‬‬ ‫ﺣﺎﺻﺔ & ﮳ﻌﺪ اﻷˆﻞ(‪.‬‬ ‫ﺤﺰء اﻟﻌﻠ‪C‬ي اﻷ& ﮵ﻤﻦ ﻣﻦ اﻟ< ﮳ﻄﻦ ) ﮲‬ ‫ أﻟﻢ ‪j K h‬‬ ‫‪ i‬اﻟ ﮳‬ ‫ اﻟ‪K‬ﻌﺜ& ﮳< ﮵ﻦ اﻟﺰا& ٔﺪ ‪j K h‬‬  ‫ﺷ =ح & ﮴‪cK‬ﺼ< ﮵ﲇ ﻟﺤﺎﻟﺔ ‪conK‬ﺮ اﻟﺪم اﻟﻤﻨ ﮳‬ ‫ﺤﲇ )‪ &> (Sickle Cell Anemia‬﮴ﺄ& ﮶< ﮵ﺮ ﻃ‪cK‬ﺮة ‪HbS‬‬ ‫‪ i‬اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ ‪:HbS‬‬ ‫ﺤ< ﮵ﲏ ‪j K h‬‬ ‫‪.1‬اﻟ‪Kr‬ﻌ< ﮵< ﮵ﺮ اﻟ ﮳‬ ‫ﺤ< ﮵ﻦ اﻟﻤﺴ‪ €‬ول ﻋﻦ ﺳﻠﺴﻠﺔ ‪ β‬ﻟﻠﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ‪.‬‬ ‫ﺤﲇ & ﮲ﺎ‪ D‬﮴ﺞ ﻋﻦ ﻃ‪cK‬ﺮة & ﮲‪co‬ﻄ< ﮵ﺔ ‪j K h‬‬ ‫‪ i‬اﻟ ﮳‬ ‫ ‪conK‬ﺮ اﻟﺪم اﻟﻤﻨ ﮳‬ ‫‪In Class Discussion-2‬‬ ‫‪ i‬اﻟﻤﻮﺿﻊ ‪ 6‬ﻣﻦ ﺳﻠﺴﻠﺔ ‪.β‬‬ ‫ﺣﺼﺎ& ٔﺺ اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ‪.‬‬ ‫‪ i‬﮲‬ ‫ ﻫﺬه اﻟﻄ‪cK‬ﺮة & ﮴ﺴﺘ< ﮳ﺪل اﻟﺤﻤﺾ اﻷﻣ< ﮵ﲏ اﻟ‪K‬ﻌﻠ‪ &C‬﮴ﺎﻣﺎت )‪ & (E‬﮳ﺎﻟﺤﻤﺾ اﻷﻣ< ﮵ﲏ اﻟ‪cK‬ﺎﻟ< ﮵ﻦ )‪j K h (V‬‬ ‫ اﻟ‪K‬ﻌﻠ‪ &C‬﮴ﺎﻣﺎت ﻣﺸﺤ‪ &C‬﮲ﺔ ﺳﻠ< ً﮳ﺎ وﻣﺤ< ﮳ﺔ ﻟﻠﻤﺎء‪ & ،‬﮳< ﮵ﻨﻤﺎ اﻟ‪cK‬ﺎﻟ< ﮵ﻦ ﮲ﻋ< ﮵ﺮ ﻣﺸﺤ ‪C‬ن وﰷره ﻟﻠﻤﺎء‪ ،‬ﻣﻤﺎ & ﮵ﺆدي إﻟﻰ & ﮴‪K‬ﻌ< ﮵ﺮ ‪j K h‬‬ ‫‪:(Electrophoresis) i‬‬ ‫‪ i‬اﻟﺮﺣﻼن اﻟﻜﻬ=& ﮳ﺎ‪j ٔ ¤‬‬ ‫‪ &.2‬﮴ﺄ& ﮶< ﮵ﺮ اﻟﻄ‪cK‬ﺮة ﻋﲆ ﺣﺮﻛﺔ ‪j K h HbS‬‬ ‫‪ i‬ﻋﲆ ﻋ< ﮵ﻨﺔ ﻣﻦ اﻟ< ﮳=>& ﮴< ﮵ﻨﺎت )ﻣ‪t‬ﻞ اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ(‪.‬‬ ‫ﺤﺎل ﻛﻬ=& ﮳ﺎ‪j ٔ ¤‬‬ ‫‪ & ،i‬﮵ﺘﻢ & ﮴ﻄ< ﮳< ﮵ﻖ ﻣ ﮳‬ ‫‪ i‬اﻟﺮﺣﻼن اﻟﻜﻬ=& ﮳ﺎ‪j ٔ ¤‬‬ ‫ ‪j K h‬‬ ‫ﺣﺐ أو اﻟﺴﺎﻟﺐ & ﮳ﻨﺎًء ﻋﲆ ﺷﺤﻨﺎ‪ D‬﮴ﻬﺎ اﻟﺼﺎ‪ & ﮴< ﮵ﻨﺎت ‪ D‬﮴ﻬﺎ ﮳‬ ‫ﺤﺬا& ً﮳ﺎ‬ ‫‪ i‬اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ اﻟﻌﺎدي )‪ & ،HbA (α2β2 A‬﮴ﺤﺘ‪C‬ي ﺳﻠﺴﻠﺔ ‪ β‬اﻟﻌﺎد& ﮵ﺔ ﻋﲆ ﮲ﻋﻠ‪ &C‬﮴ﺎﻣﺎت ﺳﺎﻟ< ﮳ﺔ اﻟﺸﺤﻨﺔ‪ ،‬ﻣﻤﺎ & ﮵ ﮳‬ ‫ﺤﻌﻞ ‪ HbA‬أﻛ‪t‬ﺮ ا& ﮲ ﮳‬ ‫ ‪j K h‬‬ ‫‪Will’s hemoglobin, HbS, is composed of two normal α chains and two β-globin chains with‬‬ ‫ﺣﺐ أ‪¥‬ﻨﺎء اﻟﺮﺣﻼن اﻟﻜﻬ=& ﮳ﺎ‪j ٔ ¤‬‬ ‫‪.i‬‬ ‫& ﮲ﺤﻮ اﻟ‪co‬ﻄﺐ اﻟﻤﻮ ﮳‬ ‫ﺤﲇ )‪ & ،HbS (α2β2 S‬﮴ﻤﺖ إزاﻟﺔ ﺷﺤﻨﺔ ﺳﺎﻟ< ﮳ﺔ )& ﮳ﺴ< ﮳ﺐ اﺳﺘ< ﮳ﺪال اﻟ‪K‬ﻌﻠ‪ &C‬﮴ﺎﻣﺎت & ﮳ﺎﻟ‪cK‬ﺎﻟ< ﮵ﻦ(‪ ،‬ﻣﻤﺎ & ﮵ﺆدي إﻟﻰ ﺣﺮﻛﺔ‬ ‫‪ i‬اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ اﻟﻤﻨ ﮳‬ ‫ ‪j K h‬‬ ‫‪the sickle cell variant (α2β2 S ). The change in amino acid composition from a glutamate to‬‬ ‫‪ i‬ﻣ‪co‬ﺎ[& ﮲ﺔ & ﮳ـ ‪.HbA‬‬ ‫ﺤﺎل اﻟﻜﻬ=& ﮳ﺎ‪j ٔ ¤‬‬ ‫‪ i‬اﻟﻤ ﮳‬ ‫ﺤ‪r‬ﻠ‪cK‬ﺔ ‪j K h‬‬ ‫أ& ﮳ﻄﺄ أو ﻣ ﮲‬ ‫‪.3‬اﻟ‪= cK‬ق & ﮳< ﮵ﻦ اﻷ‪nK‬ﺮاد اﻟﻤﺼﺎ& ﮳< ﮵ﻦ واﻟﻤﺘﺤﻤﻠ< ﮵ﻦ ﻟﻠﻤﺮض‪:‬‬ ‫‪a valine in the β chain allows sickle hemoglobin to be separated from normal adult‬‬ ‫ﺤﲇ ‪conK‬ﻂ‪.‬‬ ‫ اﻷ‪nK‬ﺮاد اﻟﻤﺼﺎ& ﮳‪C‬ن )‪:(Homozygous, HbSS‬‬ ‫ﺣ< ﮵ﻦ ‪ ،HbS‬ﻣﻤﺎ & ﮵ﺆدي إﻟﻰ & ﮴ﻜ‪ &C‬﮵ﻦ اﻟﻬ< ﮵ﻤﻮ﮲ﻋﻠ‪ &C‬﮳< ﮵ﻦ اﻟﻤﻨ ﮳‬ ‫ﺤﺘ< ﮵ﻦ ﻣﻦ ﮳‬ ‫ & ﮵ﻤ‪r‬ﻠﻜ ‪C‬ن & ﮲ﺴ ﮲‬ ‫‪hemoglobin (HbA, or [α2β2 A]) by electrophoresis. In electrophoresis, an aliquot of blood‬‬ ‫ﺤ< ﮵ﻦ‪ ،‬ﻣﻤﺎ & ﮵ﺴ< ﮳ﺐ‪:‬‬ ‫ﺣﺎﺻﺔ ﻋﻨﺪ & ﮲‪co‬ﺺ اﻷﻛﺴ ﮳‬ ‫ﺤﻞ & ﮳ﺸ ﻞ ﻣﺘﻜ=ر‪ ،‬﮲‬‫ﺣﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء ﻟﺪ‪ D‬﮵ﻬﻢ ‪rq‬ﻌﺮض ﻟﻠﺘﻤﻨ ﮳‬ ‫ ا& ﮲ﺴﺪاد اﻷوﻋ< ﮵ﺔ اﻟﺪﻣ‪ &C‬﮵ﺔ اﻟﺼ‪K‬ﻌ< ﮵ﺮة )‪.(vaso-occlusive crisis‬‬ ‫ ﮲‬ ‫ﺤﺔ )‪ ،(ischemia‬ﻣﻤﺎ & ﮵ﺴ< ﮳ﺐ ¨ﻻًﻣﺎ ﺣﺎدة‪.‬‬ ‫‪ i‬اﻷ& ﮲ﺴ ﮳‬ ‫ﺤ< ﮵ﻦ ‪j K h‬‬ ‫ & ﮲‪co‬ﺺ اﻷﻛﺴ ﮳‬ ‫‪or other solution containing proteins is applied to a support, such as paper or a gel. An‬‬ ‫ﺤﻼ&ﺎ﮵ اﻟﺪم اﻟﺤﻤﺮاء & ﮳ﻮاﺳﻄﺔ اﻟﻄﺤﺎل‪ ،‬ﻣﻤﺎ & ﮵ﺆدي إﻟﻰ ‪conK‬ﺮ اﻟﺪم اﻟﻤﺰﻣﻦ‪.‬‬ ‫ اﻷ‪nK‬ﺮاد اﻟﺤﺎﻣﻠ ‪C‬ن ﻟﻠﻄ‪cK‬ﺮه )‪:(Heterozygous, HbAS - Sickle Cell Trait‬‬ ‫ & ﮴ﻜﺴ< ﮵ﺮ ﺳ=‪ D‬﮵ﻊ ﻟ ﮲‬ ‫‪electrical field is applied and the proteins migrate a distance toward the anode (negative‬‬ ‫ﺤﻌﻞ ﻟﺪ‪ D‬﮵ﻬﻢ ﻛﻤ