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1. Introduction to Medical Biochemistry
2. CARBOHYDRATES OF BIOLOGICAL SIGNIFICANCE
3. LIPIDS OF BIOLOGICAL SIGNIFICANCE
4. AMINO ACIDS OF BIOLOGICAL SIGNIFICANCE
5. PROTEINS OF BIOLOGICAL SIGNIFICANCE
6. PROTEINS OF EXTRACELLULAR MATRIX
11- Molecular Biology AND GENETICS
1. Introduction to Medical Biochemistry
1.1. Water:
1.1.1. Molecular structure of water
1.1.2. Noncovalent forces : hydrogen bonds, electrostatic interactions, Van der Waals forces and hydrophobic interactions
1.1.3. roperties of water: thermal properties of water, solvent properties of water and dissociation and pH of water
1.1.4. Law of mass action, equilibrium constant and ionic product constant of water
1.1.5. pH and pOH
1.2. Acids and Bases
1.2.1. Normal and molar solutions
1.2.2. True acidity and titratable acidity
1.2.3. Indicators
1.3. Buffers: composition and types, mechanism of Action, physiological buffers, acidosis and alkalosis.
1.4. Solutions: diffusion, osmosis, osmotic pressure (O.P.), isotonic solutions, importance of osmotic pressure, viscosity, surface tension, hydrotropy, adsorption and elution.
1.5. Types of Solutions
1.5.1. True or Crystalloidal Solutions
1.5.2. Colloidal Solutions
1.5.3. Suspensions
1.6 Colloidal Solutions: emulsoids and suspensoids
Properties of Colloidal Solutions: tyndall effect, brownian movements, precipitation, filtration, dialysis, colloidal osmotic pressure (oncotic pressure) and fractionation of colloids (precipitation, ultra-centrifugation, electrophoresis).
1.7. Isomerism
- Structural Isomerism: chain isomerism, functional group isomerism and position isomerism
- Stereo Isomerism: geometrical isomerism and optical isomerism
By the end of this course the student should be familiar with the different ways of expression of concentration of substances and should be able to convert one form to another. He should understand what is meant by pH, how to measure the pH, how does the body maintain the pH constant, and how this may be deranged in different conditions and diseases. He should be able to interpret the significance of variation from normal in the pH and electrolyte composition of the blood. He should be able to relate information on pH and electrolyte concentrations to possible metabolic and respiratory imbalance.The student should also be familiar with terms like osmotic pressure, viscosity, surface tension, hydrotropy, adsorption, elution and colloids. He should be able to calculate the osmotic pressure of a solution and should understand the physiological importance of surface tension and osmotic pressure. The student should also get acquainted with the functional groups important in biochemical reactions and the different types of isomerism.
2. CARBOHYDRATES OF BIOLOGICAL SIGNIFICANCE
2.1. Monosaccharides
2.1.1. Classification of monosaccharides:
2.1.1.1. Trioses : Glyceradehyde and dihydroxyacetone
2.1.1.2. Tetroses : Erythrose and erythrulose
2.1.1.3. Pentoses : Ribose and ribulose
2.1.1.4. Hexoses : Glucose, galactose, mannose and fructose
2.1.1.5. Heptoses : sedoheptulose
2.1.2. Stereochemical isomers of monosaccharides
2.1.3. Optical Activity, Plane Polarized Light & (PPL) specific Rotation
2.1.4. Cyclic forms of monosaccharides (anomeric forms) & mutarotation
2.1.5. Chemical Properties of Monosaccharides
2.1.5.1. Action of acids and alkalis
2.1.5.2. Oxidation of monosaccharides: aldonic acids, aldaric acids and uronic acids
2.1.5.3. Reduction (Sugar Alcohols)
2.1.5.4. Reducing properties of monosaccharides
2.1.5.5. Ester Formation
2.1.5.6. Glycoside Formation
2.1.6. Importance of monosaccharides
Important derivatives of monosaccharides: Sugar acids( aldonic acids, uronic acids, L-ascorbic acid), sugar alcohols (glycerol, ribitol, myo-inositol), deoxysugars (deoxyribofuranose and L-fucose), aminosugars, sialic acid and glycosides
2.2. Oligosaccharides
2.2.1. Disacharides:
2.2.1.1. Reducing disaccharides: maltose, isomaltose, cellobiose and lactose
2.2.1.2. Non-reducing disaccharides: sucrose
2.2.2. ABO Blood Group Antigens
2.3. Polysaccharides
2.3.1. Homopolysaccharides: Starch (amylose & amylopectin), dextrins, glycogen, cellulose and inulin
2.3. 2. Heteropolysaccharides or GAGs: Hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin and heparan sulfate
2.4. Proteoglycans: Functions of GAGs and proteoglycans
By the end of this course the student should be acquainted with the different types of carbohydrates especially those present in the human body, as well as their importance. He should be able to know the structure and some of the properties of carbohydrates.
3. LIPIDS OF BIOLOGICAL SIGNIFICANCE
3.1. Classification of Lipids (Simple Lipids, Conjugated & Derived Lipids)
3.2. Fatty Acids
3.2.1. Saturated Fatty Acids (SFA): Short chain fatty acids and long chain fatty acids
3.2.2. Unsaturated Fatty Acids (USFA): monoenoic (monoethenoid) acids and polyenoic (polyethenoid) acids (w3 PUFA and w6 PUFA)
3.2.3. Nutritional Classification of Fatty Acids
3.2.4. Essential fatty acids and non-essential fatty acids
3.2.5. Properties of fatty acids: Melting point, solubility, ester formation, salt formation, reduction, properties due to presence of double bonds (addition of hydrogen, iodine and oxygen)
3.3. Eicosanoids:
3.3.1. Chemistry of prostanoids: prostaglandins (PG), thromboxanes (TX) and prostacyclins(PGI)
3.3.2. Leukotrienes and lipoxins
4.4. Simple Lipids
4.4.1. Neutral fats: Oils and solid Fats
4.4.1.1. Physical properties
4.4.1.2. Chemical properties: hardening, iodine number, saponification, hydrolysis by acids and rancidity
4.4.2. Waxes
4.5. Conjugated Lipids (Compound Lipids)
4.5.1. Phospholipids
4.5.2. Glycerophosphatides (phosphoglycerides): phosphatidic acid, lecithin, cephalin phosphatidyl-serine, phosphatidyl-inositol, plasmalogens, cardiolipins and lysophospholipids
4.5.3. Sphingomyelin
4.5.4. Importance and functions of phospholipids including role of phospholipase c as second hormone messenger.
4.5.5. Glycolipids and their importance: cerebrosides, sulfolipids and gangliosides
4.6. Derived lipids
4.6.1. Steroids:
4.6.1.1. Sterols (Phyto-sterols, Myco-sterols & Zoo-sterol) and their importance
4.6.1.2. Bile acids: primary bile acids and secondary bile acids and bile salts
4.6.1.3. Steroid hormones: sex hormones (androgens, estrogens and progesterone), adrenocortical hormones (glucocorticoids and mineralocorticoids)
4.6.2. Carotenoids (Terpenes): a, b, and g carotenes and cryptoxanthine
By the end of this course the student should be acquainted with the different types of lipids especially those present in the human body, as well as their importance. He should be able to know the structure and some of the properties of lipids. He should comprehend the structural differences between the different steroid hormones and should have an idea about their structural activity relationship. He should also understand how lipids interact with aqueous phases with particular emphasis on the plasma lipoproteins
4. AMINO ACIDS OF BIOLOGICAL SIGNIFICANCE
4.1. Classifications of amino acids according to the nature of radical (R): aliphatic amino acids, aromatic amino acids and heterocyclic amino acids. Sulfur containing amino acids and hydroxy-amino acids.
4.2. Classifications of amino acids according to the polarity of radical (R): neutral amino acids, basic amino acids and acidic amino acids.
4.3. Nutritional classifications of amino acids: essential, half-essential and non-essential amino acids.
4.4. Properties of Amino Acids: optical activity, amphoteric properties and peptide formation.
By the end of this course the student should be acquainted with the different amino acids which are the structural elements of protein conformation. He should also know some of their properties particularly those relevant to the structure and properties of proteins.
5. PROTEINS OF BIOLOGICAL SIGNIFICANCE
5.1. Biochemical importance and functions of proteins: enzymes. structural proteins, defense mechanisms, regulation of body functions, transport and storage
5.2. The conformation of proteins (structure of proteins)
5.2.1. Primary structure
5.2.2. Secondary Structure: Regular secondary structure: a-helix and b-pleated sheets, other forms of secondary structure: loop regions, b-bends and disordered regions
5.2.3. Supersecondary structure (motifs)
5.2.4. Tertiary structure and domains
The types of interactions that stabilize the protein tertiary structure: hydrophobic interactions, electrostatic interactions, hydrogen bonds and disulfide bonds
5.2.5. Quaternary Structure: fibrous and globular proteins
5.3. Properties of proteins: solubility, salting out, amphoteric properties and iso-electric point (I.E.P) and denaturation of proteins
5.4. Isolation and purification of proteins: ultracentrifugation, salting out, dialysis, chromatography and electrophoresis
5.5. Classification of proteins: simple proteins and conjugated proteins
5.5.1. Simple Proteins: Protamines, histones, albumins, globulins, gliadins, glutelins and scleroproteins (mainly keratin, collagen and elastin)
5.5.2. Conjugated Proteins: Phosphoproteins, lipoproteins, glycoproteins (N-linked and O-linked types), metalloproteins [containing iron (Fe), copper (Cu), magnesium (Mg), manganese (Mn) and zinc (Zn)], chromoproteins and nucleoproteins
5.6. Biological active proteins, peptides and amino acid derivatives
The student should also properly understand the levels of protein conformation and its importance in determining their properties. He should be able to analyze the interaction of proteins with large and small molecules. He should be able to relate structural properties of particular proteins to their biologic function in health and disease. He should know examples of different types of proteins and their functions.
6. PROTEINS OF EXTRACELLULAR MATRIX
(CONNECTIVE TISSUE PROTEINS)
6.1. Collagen: Structure of topocollagen, amino acid composition of a-chain and synthesis of collagen a-chain, fibril and fiber.
6.2. Elastin: Structure and functions.
6.3. Other proteins: Fibronectin, laminin and fibrillin
6.4. Bone Proteins: Collagenous proteins and non- collagenous proteins (osteocalcin, osteonectin, different types of proteoglycans, fibronectin, osteopontin and bone sialoprotein)
6.5. Cartilage proteins: Collagenous proteins and non-collagenous proteins: aggregating cartilage proteoglycan ( aggrecan), large non-aggregating proteoglycans and chondronectin
The student should properly understand the protein of extracellular matrix and their importance. He must understand the relation between their structure and function and the importance of bone and cartilage proteins.
7.1. Chemistry of heme and hemoproteins
7.2. Myoglobin: structure and functions
7.3. Hemoglobin: HbA and HbA2, hemoglobin derivatives (oxyhemoglobin (R & T Forms), effect of 2,3-Bisphosphoglycerate (BPG), carbaminohemoglobin (Bohr Effect), carboxyhemoglobin and methemoglobin (Met-Hb)
7.4. Organization of the globin gene families (a-gene family and b-gene family)
7.5. Other Types of hemoglobin:
7.5.1. Fetal hemoglobin (HbF)
7.5.2. Abnormal hemoglobins (Hemoglobinopathies): Sickle-cell anemia (HbS), met-hemoglobinemia (Hb M) and hemoglobin C (Hb C).
7.5.3. Thalassemia: a-thalassemias and b-thalassemias
7.6. Other Hemoproteins
7.6.1. Different types of cytochromes: cytochromes present in the electron transport chain (ETC), and cytochromes P450.
7.6.2. peroxidases, catalase, nitric oxide synthase and tryptophan doxygenase (pyrrolase)
The student should properly understand the chemistry of heme and hemoproteins and understand the different types of hemoproteins and their functions. He has to be oriented with the different types of hemoglobin (normal and abnormal types), the organization of globin genes and the different types of gene mutation that may result in diseases.
8.1. Immune response: The humoral and the cellular immune responses.
8.1.1. Antigens: immunogens and haptens
8.1.2. Primary and secondary immune response
8.2. General structure of immunoglobulins, genes producing immunoglobulins and antibody diversity
8.3. Structures and functions of different immunoglobulins (IgG, IgM, IgA, IgD & IgE)
8.4. Acquired immune deficiency syndrome (AIDS)
By the end of this course the student should know the primary and secondary immune response, structure and functions of different immunoglobulins, genes producing immunoglobulins and antibody diversity.
9.1. Membrane lipids and lipid bilayer of membranes: phospholipids, glycolipids and cholesterol
9.2. Membrane Proteins (fluid mosaic model): Types and importance of membrane proteins: integral proteins (transmembrane proteins) and peripheral proteins.
9.3. Membrane carbohydrates and their importance.
9.4. Membrane asymmetry and fluidity.
9.5. Diseases due to mutations affecting genes encoding membrane proteins.
By the end of this course the student should know the structural arrangement of cell membrane, how lipid, carbohydrates and proteins interact to control and regulate cell membrane properties and functions.
10.1. Nitrogenous bases: pyrimidines and purines, tautomerism, minor bases in nucleic acids, methylated purines of dietary origin
10.2. Nucleosides and nucleotides
10.3. Free Nucleosides and nucleotides:
10.3.1. Adenine nucleotides: AMP, ADP, ATP, cAMP as second hormone messenger, active methionine or (SAM), 3`-phospho-adenosine-5`-phospho sulfate (PAPS) and coenzymes containing adenine (Derivatives of Vitamins).
10.3.2. Guanine nucleotides: GMP, GDP, GTP and cGMP, role of G-proteins in signal transduction.
10.3.3. Cytosine nucleotides: CMP, CDP, CTP, CDP-choline, CDP-ethanolamine or CDP-diacylglycerol
10.3.4. Uracil nucleotides: UMP, UDP, UTP, UDP-Glc, UDP-Gal and UDP-GlcUA.
By the end of this course the student should know the different purines and pyrimidines entering in the formation nuelcosides and nuelcotides. The student should also get acquainted with the free nucleotides of biological importance, particularly their role in signal transduction, as second messenger of hormone action and as coenzymes.
11- Molecular Biology AND GENETICS
11.1 CHEMISTRY OF NUCLEIC ACIDS
11.1.1. Deoxyribonucleic Acid: DNA primary and secondary structure, denaturation of DNA. DNA tertiary structure: DNA supercoiling (toroidal and interwound) and types of supercoiling in circular DNA (right-handed and left-handed supercoil or superhelix).
11.1.2. Structure of chromatids and chromosomes: nucleosomes, 10-nm fibril, 30-nm fiber, protein scaffold and rosette, chromatid and chromosome arrangements. This includes the need for histones: packaging of DNA, significance of the cationic nature of histones and packaging role of H1.
11.1.3. The human genome
Other forms of nuclear DNA: A form of DNA and Z Form of DNA, triple-stranded DNA (Triplex) or (H-DNA) and four-stranded DNA (quadruplex)
11.1.4. Mitochondrial DNA (mtDNA)
11.1.5. Ribonucleic Acid (RNA): strucvture of different types of RNA (rRNA, tRNA and mRNA.
11.1.6. Composition of Viruses
11.1.7. Prokaryotic DNA and Chromosomes
By the end of this course the student should know the different purines and pyrimidines entering in the formation of nucleic acids. He should understand the structure of DNA and different types of RNA. He should also have an idea about their function. He should be able to explain how the structural features of nucleic acids allow them to store and express information. He must understand the different levels of gene organization, what is a gene and a genome.
11.2. DNA Synthesis (Replication)
11.2.1. Principles of replication
11.2.2. Prokaryotic Replication: Separation of the two complementary strands of DNA, formation of two replication forks, synthesis of the leading and lagging strands of DNA and role of different DNA polymerases (I, II,III)
11.2.3. Eukaryotic Replication: multiple origin of replication, synthesis of the leading and lagging strands of DNA, role of different DNA polymerases (a, b, g, d and e) and telomerase.
11.2.4. Comparison between eukaryotic and prokaryotic replication
11.2.5. DNA repair (Xeroderma pigmentosum or XP)
11.3. SYNTHESIS OF RNA (TRANSCRIPITION)
11.3.1. General principles
11.3.2. Prokaryotic RNA synthesis
Properties of prokaryotic RNA polymerase: The RNA polymerase holoenzyme (sigma factor (subunit) and core enzyme. Steps: initiation, elongation and termination ( r-dependent termination and r- independent termination).
11.3.3.Euokaryotic RNA synthesis
General principles, types of RNA polymerases. Transcription phases: initiation, elongation and termination.
11.3.4. Synthesis of mRNA: Gene organization, initiation of transcription, general transcription factors (GTFs) for RNA polymerase II (TF II), elongation and termination. Processing of mRNA (capping, polyadenyaltion and splicing).
Synthesis of rRNAs and of tRNAs
11.3.5. Regulation of prokaryotic gene expression
Inducible and constitutive genes, operon model: Lac operon model of E-Coli, repression and derepression (or induction)
11.3.6. Regulation of euokaryotic gene expression
Alteration of gene content: gene amplification, gene diminution and gene rearrangement or recombination e.g. immunoglobulin genes. Transcriptional regulation: chromatin remodeling, cytosine methylation (gene silencing) and histone acetylation. DNA regulatory region: basal expression elements, regulated expression elements (enhancers and silencers), other regulatory elements (hormone response elements or HRE ) and DNA regulatory factors. Post-transcriptional regulation: alternative splicing and regulation of RNA stability
11.4. PROTEIN SYNTHESIS (TRANSLATION)
11.4.1. Genetic code: characters of genetic code, wobble hypothesis and reading frames
11.4.2. Steps of protein synthesis: synthesis of aminoacyl-tRNA, synthesis of polypeptide chain (initiation, elongation and termination)
11.4.3. Protein folding: Cis-trans- prolyl isomerases, protein disulfide isomerases and chaperone proteins.
11.4.4. Post-translation processing of proteins: trimming and covalent alteration (phosphorylation, glycosylation, hydroxylation, carboxylation, other covalent modification).
11.4.5. Gene Mutations: Causes of mutations. Types of mutations:1) base substitutions (point mutations): transition and transversion. missense, nonsense and silent mutations, 2) deletion of one or more bases: frameshift mutation and deletion of three or multiple of three base pairs,3) insertion of one or more bases: frameshift and additions of three or multiple of three bases.
11.5. CELL CYCLE – APOPTOSIS - CARCINOGENESIS
11.5.1. Cell cycle: The resting phase (G0), the different phases of cell cycle: Gap 1 phase (G1), synthesis phase (S phase), Gap 2 phase (G2) and mitosis (M phase). Control of cell cycle: cyclins, cyclin-dependent kinases (CDK) and cyclin-kinase inhibitors (CIP). Cell cycle restriction point and checkpoints
11.5.2. Apoptosis: receptor-mediated apoptosis and role of p53.
11.5.3. Development of cancer
11.5.4. Tumor suppressor genes: Rb ( Retinoblastoma) tumor suppressor gene and p53 tumor suppressor gene.
11.5.5 Prot-oncogenes and oncogenes: mechanisms for conversion of proto-oncogenes to oncogenes
11.5.6. Tumor markers
11.6. RECOMBINANT DNA TECHNOLOGY
11.6.1. Restriction enzymes (restriction endonucleases) and restriction maps.
11.6.2. Polymorphism: single nucleotide polymorphism, RFLP, minisatellite polymorphism and microsatellite polymorphism (DNA fingerprinting).
11.6.3. DNA amplification techniques: DNA cloning and polymerase chain reaction or PCR
11.6.4. DNA Libraries: genomic DNA libraries and complementary DNA (cDNA) libraries
11.6.5. Probes and nucleic acid hybridization
11.6.6. Separation and identification of DNA: southern blotting, northern blotting and western Blotting
11.6.7. DNA sequencing and microarray
11.6.8. Prenetal diagnosis of genetic diseases: diagnosis of sickle cell anemia
11.6.9. Gene therapy: Ex vivo gene delivery and in vivo gene delivery. Techniques of gene therapy or delivery methods[ viral delivery methods and non-viral delivary systems. Challenges facing gene therapy
11.6.10.The human genome project: major goals for the HGP, the human genome diversity project, comparative genomics, model organisms, Caenorhabditis eIegans, Mice (key models of human disease), genome modification, transgenic animals and cloning animals (Dolly).
11.6.11. The human proteome project: Explanation of the proteomes and proteomics and the major goals and benefits of human proteome project
By the end of molecular biology course the student should be able to understand how are nucleic acids synthesized and catabolized and the relation of this to cell multiplication and protein synthesis. Also, the student should be able to understand how are proteins synthesized in our body, how is this regulated, and how may errors in this process lead to diseases like sickle cell anemia and thalassemia. Also, the student should be able to know the general principles of genetic engineering and how may this be used for the diagnosis and management of diseases. He must acquainted with the different techniques of gene therapy and their applications. He must be oriented with major goals and benefits of the human genome and proteome projects.