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![Sickle cell anemia (hemoglobin S disease)
• Sickle cell anemia is a homozygous, recessive disorder. It occurs in
individuals who have inherited two mutant genes (one from each
parent) that code for synthesis of the β chains of the globin molecules.
[Note: The mutant β-globin chain is designated βS, and the resulting
hemoglobin, α2βS2, is referred to as Hb S]. An infant does not begin
showing symptoms of the disease until sufficient Hb F has been
replaced by Hb S so that sickling can occur.
• Heterozygotes have one normal and one sickle cell gene. The blood
cells of such heterozygotes contain both Hb S and Hb A. These
individuals have sickle cell trait. They usually do not show clinical
symptoms and can have a normal life span.](https://image.slidesharecdn.com/week1phs3022022-220907202330-0ba74b05/75/week-1-PHS-302-2022-pptx-62-2048.jpg)
week 1 PHS 302 2022.pptx
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- 2. Textbook • Lippincott IllustratedReviews: Biochemistry (Lippincott Illustrated Reviews Series) 7th Edition
- 3. No List ofTopics Contact Hours 1 Introductionto biochemistry Amino acids and protein structure 5 2 Lipid structure & carbohydrates structure 5 3 Enzymes (types, functions, role in diagnosis of some diseases) Vitamins and minerals (types, functions, and deficiencies) 5 4 Introduction to metabolism & Respiratory chain & oxidative phosphorylation Carbohydrates digestion & Glycolysis 5 5 Examination #1 Krebs cycle Gluconeogenesis Glycogen synthesis and breakdown 5 6 Lipid digestion & metabolism 5 7 Cholesterol & lipoproteins & Ketone bodies 5 8 Nitrogen metabolism 5 9 Integration of metabolism Metabolic abnormalities 5 10 Molecular biology (nucleic acid structure, replication, transcription & translation) & Biotechnology 5 Final exam 2
- 4. # Assessment taskWeek Due Percentage ofTotal Assessment Score 1 Exam 1 (multiple choice, short answer and involving concepts discussed in class and from assigned readings) 5 30% 2 Class Participation (quizzes, Medical report, Lecture presentation) 1-10 30% 3 Exam 2 Cumulative final examination using the same format as the summary exams 11 40% Assessment
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- 6. Objectives By the endof this lecture, the students should understand the following: • Definition of biochemistry • Definition of biomolecules • Classification of biomolecules • Types and general functions of proteins, carbohydrates, and lipids • Structure and function of Amino acids and Proteins
- 7. What is Biochemistry? Biochemistryis a branch of medical science that describes the structure, organization and functions of living matter in molecular terms. It is the chemistry of life. It is divided into 3 principal areas: • 1. Structural chemistry • 2. Metabolism • 3. Chemistry of molecular genetics
- 8. Biomolecules • Chemicals ormolecules present in the living organisms are known as Biomolecules. • Just like cells are building blocks of tissues likewise molecules are building blocks of cells.
- 11. Amino acids • Buildingblocks of proteins. • 20 commonly occurring. • Contains amino group and carboxyl group function groups (behavioral properties) • R Group (side chains) determines the chemical properties of each amino acids. • Also determines how the protein folds and its biological function. • Individual amino acids in protein connected by peptide bond. • Functions as transport proteins, structural proteins, enzymes, antibodies, cell receptors.
- 12. Carbohydrates •most abundant organicmolecule found in nature. •Initially synthesized in plants from a complex series of reactions involving photosynthesis. •Basic unit is monosaccharides. •Monosaccharides can form larger molecules e.g. glycogen, plant starch or cellulose. Functions: Provide and store energy, Supply carbon for synthesis of other compounds, Form structural components in cells and tissues, Intercellular communications
- 13. lipids Example of lipidsare • triacylglycerol, • streiods (cholestrol, sex hormones), • fat soluble vitamins. Insoluble in water Functions • Storage of energy in the form of fat • Membrane structures • Insulation (thermal blanket) • Synthesis of hormones
- 15. Amino acids andprotein structures Dr. Asmaa Saleh Ali
- 16. Definition: Amino acids arebuilding blocks of protein (Proteins are polymers of amino acids linked by peptide bond) Importance of amino acids: building blocks of proteins Precursors for non protein specialized products (histamine, GABA) energy source
- 17. 1- enzymes 2- hormones 3-structural 4- transport 5- immunoglobulins 6- clotting factors 7- complements 8- buffers Importance of proteins:
- 19. Amino Acid Structure •More than 300 amino acids have been discover • In mammals, 20 amino acids make up every protein • Each amino acid contains a carboxyl group • Each amino acid contains a primary amino group except for proline which has a secondary amino group • A side chain (R) is present in every amino acid and is connected to the α carbon
- 20. Amino Acid Structure •Each amino acid contains a primary amino group except for proline which has a secondary amino group
- 21. Amino Acid Structure •The human body function at a physiological pH of 7.4 • At this physiological pH, both the carboxyl group and the amino group dissociate • The carboxyl group dissociate to give the negatively charged carboxylate ion ( COO–) • While the amino part is protonated to form a positively charged amine ( NH3+) • The role of any amino acid is decided according to the nature of the side chain (R)
- 22. Amino Acid Classification •Each amino acid is classified according to the chemical properties of the side chain • As a result, the 20 amino acids are divided into polar and non-polar amino acids • Polar amino acid is further classified at physiological pH to • 1- No charge polar amino acids • 2- Positively charged amino acids • 3- Negatively charged amino acids
- 23. Non-Polar Amino Acids •They has hydrophobic characteristic • They have no charge on the side chain • They have low water solubility • They create the core of most globular proteins
- 26. Polar Amino Acids Uncharged •Serine, threonine, and tyrosine each contain a polar hydroxyl group that can participate in hydrogen bond formation. • The side chains of asparagine and glutamine each contain a carbonyl group and an amide group, both of which can also participate in hydrogen bonds. • The side chain of cysteine contains a sulfhydryl group (–SH), which is an important component of the active site of many enzymes
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- 30. Optical properties ofamino acids • The α-carbon of an amino acid is attached to four different chemical groups and is, therefore, a chiral or optically active carbon atom. • Glycine is the exception because its α-carbon has two hydrogen substituents and, therefore, is optically inactive. Amino acids that have an asymmetric center at the α-carbon can exist in two forms, designated D and L, that are mirror images of each other. • The two forms in each pair are termed stereoisomers, optical isomers, or enantiomers. All amino acids found in proteins are of the L- configuration. However, D-amino acids are found in some antibiotics and in plant and bacterial cell walls.
- 31. Optical properties ofamino acids
- 32. • In nutrition,amino acids are classified as either essential or non- essential. These classifications resulted from early studies on human nutrition, which showed that specific amino acids were required for growth or nitrogen balance even when there is an adequate amount of alternative amino acids. • Nonessential amino acids can be made by the body, while essential amino acids cannot be made by the body so you must get them from your diet. • You must have all of the amino acids so your body can build the wide variety of proteins it needs. Dietary classification of Amino Acids
- 33. Dietary classification ofAmino Acids
- 34. Structure of Proteins •The 20 amino acids commonly found in proteins are joined together by peptide bonds. • The linear sequence of the linked amino acids contains the information necessary to generate a protein molecule with a unique three-dimensional shape. • The complexity of protein structure is best analyzed by considering the molecule in terms of four organizational levels, namely, primary, secondary, tertiary, and quaternary
- 36. I- Primary structureof proteins • The sequence of amino acids in a protein is called the primary structure of the protein. • Understanding the primary structure of proteins is important because many genetic diseases result in proteins with abnormal amino acid sequences, which cause improper folding and loss or impairment of normal function. • If the primary structures of the normal and the mutated proteins are known, this information may be used to diagnose or study the disease.
- 37. Peptide bond • Inproteins, amino acids are joined covalently by peptide bonds, which are amide linkages between the α- carboxyl group of one amino acid and the α-amino group of another. • Peptide bonds are not broken by conditions that denature proteins, such as heating or high concentrations of urea. • Prolonged exposure to a strong acid or base at elevated temperatures is required to hydrolyze these bonds non enzymically.
- 38. II- Secondary structureof proteins • The polypeptide backbone forms regular arrangements of amino acids that are located near to each other in the linear sequence. • These arrangements are termed the secondary structure of the polypeptide. • The α-helix and β-sheet are examples of secondary structures frequently encountered in proteins
- 39. α-Helix • Several differentpolypeptide helices are found in nature, but the α-helix is the most common. • It is a spiral structure, consisting of a tightly packed, coiled polypeptide backbone core, with the side chains of the component amino acids extending outward from the central axis to avoid interfering sterically with each other
- 41. β-Sheet • The β-sheetis another form of secondary structure in which all of the peptide bond components are involved in hydrogen bonding. • The surfaces of β-sheets appear “pleated,” and these structures are, therefore, often called “β-pleated sheets.” • When illustrations are made of protein structure, β-strands are often visualized as broad arrows
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- 45. III- Tertiary structureof proteins • The tertiary structure of a protein refers to the overall three-dimensional arrangement of its polypeptide chain in space. • It is generally stabilized by outside polar hydrophilic hydrogen and ionic bond interactions, and internal hydrophobic interactions between nonpolar amino acid side chains
- 46. III- Tertiary structureof proteins • Based upon their tertiary structure, proteins are often divided into globular or fibrous types. • Fibrous proteins, like α-keratin, have elongated rope-like structures that are strong and hydrophobic. • Globular proteins, like the plasma proteins and the immunoglobulins, are more spherical and hydrophilic.
- 49. IV- Quaternary StructureOf Proteins • Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins. However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated. • The arrangement of these polypeptide subunits is called the quaternary structure of the protein
- 51. Denaturation of proteins •Protein denaturation results in the unfolding and disorganization of the protein’s secondary and tertiary structures, which are not accompanied by hydrolysis of peptide bonds. • Denaturing agents include heat, organic solvents, mechanical mixing, strong acids or bases, detergents, and ions of heavy metals such as lead and mercury. • Denaturation may, under ideal conditions, be reversible, in which case the protein refolds into its original native structure when the denaturing agent is removed. However, most proteins, once denatured, remain permanently disordered.
- 53. Protein Misfolding • Proteinfolding is a complex, trial-and-error process that can sometimes result in improperly folded molecules. • These misfolded proteins are usually tagged and degraded within the cell. • However, this quality control system is not perfect, and intracellular or extracellular aggregates of misfolded proteins can accumulate, particularly as individuals age. • Deposits of these misfolded proteins are associated with a number of diseases.
- 54. • Disease canoccur when an apparently normal protein assumes a conformation that is cytotoxic, as in the case of Alzheimer disease and the transmissible spongiform encephalopathies (TSEs), including Creutzfeldt-Jakob disease. • In Alzheimer disease, normal proteins, after abnormal chemical processing, take on a unique conformational state that leads to the formation of neurotoxic amyloid protein assemblies consisting of β- pleated sheets. • In TSEs, the infective agent is an altered version of a normal prion protein that acts as a “template” for converting normal protein to the pathogenic conformation. Protein Misfolding
- 57. Structure of Heme Examplesof hemoproteins Myoglobin and Hemoglobin
- 58. Myoglobin • Myoglobin, ahemeprotein present in heart and skeletal muscle, functions both as a reservoir for oxygen, and as an oxygen carrier that increases the rate of transport of oxygen within the muscle cell. Myoglobin consists of a single polypeptide chain that is structurally similar to the individual subunit polypeptide chains of the hemoglobin molecule. It is a globular protein.
- 59. Hemoglobin • Hemoglobin isfound exclusively in red blood cells (RBCs), where its main function is to transport oxygen (O2) from the lungs to the capillaries of the tissues. Hemoglobin A, the major hemoglobin in adults, is composed of four polypeptide chains (two α chains and two β chains) held together by noncovalent interactions. It is a globular protein.
- 60. Hemoglobinopathies • Hemoglobinopathies aredisorders caused either by production of a structurally abnormal hemoglobin molecule, synthesis of insufficient quantities of normal hemoglobin subunits, or, rarely, both. • The sickling diseases sickle cell anemia (Hb S disease) and hemoglobin SC disease, as well as hemoglobin C disease and the thalassemia syndromes are representative hemoglobinopathies that can have severe clinical consequences.
- 62. Sickle cell anemia(hemoglobin S disease) • Sickle cell anemia is a homozygous, recessive disorder. It occurs in individuals who have inherited two mutant genes (one from each parent) that code for synthesis of the β chains of the globin molecules. [Note: The mutant β-globin chain is designated βS, and the resulting hemoglobin, α2βS2, is referred to as Hb S]. An infant does not begin showing symptoms of the disease until sufficient Hb F has been replaced by Hb S so that sickling can occur. • Heterozygotes have one normal and one sickle cell gene. The blood cells of such heterozygotes contain both Hb S and Hb A. These individuals have sickle cell trait. They usually do not show clinical symptoms and can have a normal life span.
- 65. Sickle cell anemiais characterized by lifelong episodes of pain (“crises”), chronic hemolytic anemia with associated hyperbilirubinemia, and increased susceptibility to infections, usually beginning in early childhood.
- 66. Hemoglobin C disease •Hb C is a hemoglobin variant that has a single amino acid substitution in the sixth position of the β-globin chain. In this case, a lysine is substituted for the glutamate (as compared with a valine substitution in Hb S). • Patients homo-zygous for hemoglobin C generally have a relatively mild, chronic hemolytic anemia. These patients do not suffer from infarctive crises, and no specific therapy is required. • Hemoglobin SC disease is another of the red cell sickling diseases. • In this disease, some β-globin chains have the sickle cell mutation, whereas other β-globin chains carry the mutation found in Hb C disease.
- 68. Methemoglobinemia • Oxidation ofthe heme component of hemoglobin to the ferric (Fe3+) state forms methemoglobin, which cannot bind oxygen. This oxidation may be caused by the action of certain drugs, such as nitrates, or endogenous products, such as reactive oxygen intermediates. Also, certain mutations in the α- or β-globin chain promote the formation of methemoglobin (Hb M). • The methemoglobinemias are characterized by “chocolate cyanosis” (a brownish-blue coloration of the skin and mucous membranes) and chocolate-colored blood, as a result of the dark-colored methemoglobin. Symptoms are related to the degree of tissue hypoxia, and include anxiety, headache, and dyspnea. In rare cases, coma and death can occur. Treatment is with methylene blue, which is oxidized as Fe+3 is reduced.
- 70. Thalassemias • The thalassemiasare hereditary hemolytic diseases in which an imbalance occurs in the synthesis of globin chains. • As a group, they are the most common single gene disorders in humans. • Normally, synthesis of the α- and β-globin chains is coordinated, so that each α-globin chain has a β-globin chain partner. This leads to the formation of α2β2 (Hb A). • In the thalassemias, the synthesis of either the α- or the β-globin chain is defective
- 71. Examples of structuralproteins • Collagen and elastin are examples of common, well-characterized fibrous proteins of the extracellular matrix that serve structural functions in the body. • For example, collagen and elastin are found as components of skin, connective tissue, blood vessel walls, and sclera and cornea of the eye. • Each fibrous protein exhibits special mechanical properties, resulting from its unique structure, which are obtained by combining specific amino acids into regular, secondary structural elements
- 72. Collagen • Collagen isthe most abundant protein in the human body. A typical collagen molecule is a long, rigid structure in which three polypeptides “α chains” are wound around one another in a rope-like triple helix. • Collagen molecules contain an abundance of proline, lysine, and glycine, the latter occurring at every third position in the primary structure. Collagen also contains hydroxyproline, hydroxylysine, and glycosylated hydroxylysine, each formed by posttranslational modification.
- 73. Elastin • Elastin isa connective tissue protein with rubber-like properties in tissues such as the lung. • α1-Antitrypsin (α1-AT), produced primarily by the liver but also by tissues such as monocytes and alveolar macrophages, prevents elastin degradation in the alveolar walls. • A deficiency of α1-AT can cause emphysema and, in some cases, cirrhosis of the liver.