Med1003 Week 2 Lecture PDF

MED1003 Molecules, Cells and Genes by Siu Wai (Phyllis) TSANG, PhD TUNG WAH COLLEGE email: [email protected] Office#: 3190-6713 Prepared by SWT 2024 email: [email protected] 1 Biological macromolecules All living entities (including humans) are ma...

MED1003 Molecules, Cells and Genes by Siu Wai (Phyllis) TSANG, PhD TUNG WAH COLLEGE email: [email protected] Office#: 3190-6713 Prepared by SWT 2024 email: [email protected] 1 Biological macromolecules All living entities (including humans) are made up of cells, and each cell is made up of various atoms and biomolecules in different proportions The atoms in largest quantities in the human body are oxygen, carbon, hydrogen and nitrogen [when atoms combine, molecules are formed] Biomolecules that come with relatively large molecular weight are called macromolecules Four major classes: carbohydrates, lipids, proteins and nucleic acids Prepared by SWT 2024 email: [email protected] 2 Building blocks of macromolecules Macromolecules nucleic carbohydrates lipids proteins (polymers) acids Building blocks monosaccharide fatty acid 脂肪酸 amino acid nucleotide (monomers) 單糖 氨基酸 鹼基 glycerol 甘油 Prepared by SWT 2024 email: [email protected] 3 Big 4 macromolecules – (1) Proteins A protein is a polymer of amino acids (a.a.) In other words, amino acids are the building blocks of proteins An amino acid contains: a primary amine group (−NH2) a carboxyl group (−COOH) a hydrogen atom (−H) a variable R group (or a side chain) All linked covalently to a central carbon atom, i.e., alpha carbon (Cα) Prepared by SWT 2024 email: [email protected] 4 Amino acids A protein is a polymer of amino acids In other words, amino acids are the building blocks of proteins An amino acid contains: a primary amine group (−NH2) a carboxyl group (−COOH) a hydrogen atom (−H) a variable R group (or a side chain) All linked covalently to a central carbon atom, i.e., alpha carbon (Cα) Prepared by SWT 2024 email: [email protected] 5 Amino acids (cont’d) A protein is a polymer of amino acids In other words, amino acids are the building blocks of proteins An amino acid contains: a primary amine group (−NH2) a carboxyl group (−COOH) a hydrogen atom (−H) a variable R group (or a side chain) All linked covalently to a central carbon atom, i.e., alpha carbon (Cα) Prepared by SWT 2024 email: [email protected] 6 Amino acids (cont’d) A protein is a polymer of amino acids In other words, amino acids are the building blocks of proteins An amino acid contains: a primary amine group (−NH2) a carboxyl group (−COOH) a hydrogen atom (−H) a variable R group (or a side chain) All linked covalently to a central carbon atom, i.e., alpha carbon (Cα) Prepared by SWT 2024 email: [email protected] 7 Amino acids (cont’d) A protein is a polymer of amino acids In other words, amino acids are the building blocks of proteins An amino acid contains: a primary amine group (−NH2) a carboxyl group (−COOH) a hydrogen atom (−H) a variable R group (or a side chain) All linked covalently to a central carbon atom, i.e., alpha carbon (Cα) Prepared by SWT 2024 email: [email protected] 8 Amino acids (cont’d) A protein is a polymer of amino acids In other words, amino acids are the building blocks of proteins An amino acid contains: a primary amine group (−NH2) a carboxyl group (−COOH) α a hydrogen atom (−H) a variable R group (or a side chain) All linked covalently to a central carbon atom, i.e., alpha carbon (Cα) Prepared by SWT 2024 email: [email protected] 9  The R group of amino acids The R group can be hydrocarbons or other functional groups, such as −OH, −COOH, −NH2 … α The additional carbons in the R side chain are designated as β, γ, δ and ε ε-Amino group α-Carboxylate group carboxyl group ε δ γ β αH H 6 5 4 3 2 1 H2N H2C H2C H2C H2C C COOH R C COOH α NH2 NH2 R group α-Amino group Lysine Prepared by SWT 2024 email: [email protected] 10 Classification of amino acids All differences among various amino acids mainly depend upon their R groups Amino acids are categorized into 4 groups based on the R group characteristics as the R group can be: non-polar (e.g., –CH3) polar (e.g., –CH2OH) acidic (i.e., negatively charged; e.g., –CH2COO-) basic (i.e., positively charge; e.g., –CH2CH2CH2CH2NH3+) Prepared by SWT 2024 email: [email protected] 11 Four classes of amino acids Prepared by SWT 2024 email: [email protected] 12 Further classification of amino acids https://ib.bioninja.com.au/_Media/essential-amino-acids_med.jpeg Prepared by SWT 2024 email: [email protected] 13 Peptides When amino acids are joined together by amide bonds (or peptide bonds), they form larger molecules called peptides and proteins Carboxyl group of 1 amino acid is linked to the amino group of another amino acid Amino acids can be linked into a chain  polypeptide chain https://cdn1.byjus.com/wp-content/uploads/2023/03/Peptide-Bond-01.png Prepared by SWT 2024 email: [email protected] 14 Naming of peptides Peptides refers to the short polymer of amino acids Dipeptide (2 amino acids) Tripeptide (3 amino acids) Oligopeptide (a few amino acids) Polypeptides (many amino acids) Proteins (> 40 amino acids) Hydrolysis Condensation reaction (N-terminal) (C-terminal) Prepared by SWT 2024 email: [email protected] 15 Protein structure Proteins are extraordinarily complex, therefore simpler images highlighting specific features are useful Ribbon and space-filling models Prepared by SWT 2024 email: [email protected] 16 Protein conformation The polypeptide chain folds up to form a specific shape, i.e., conformation Proteins in their functional, folded conformations are called “native” conformations (i.e., natural status, unaltered by other agents) This conformation is the 3-D arrangement of atoms in the structure and is determined by the amino acid sequence There are 4 levels of structure in protein Primary Secondary Tertiary Quaternary Prepared by SWT 2024 email: [email protected] 17 The FOUR levels of protein structure Primary: a linear sequence of amino acids linked by covalent bonds (i.e., amide bonds) Secondary: an arrangement of adjacent amino acids in a coiled manner, e.g., α-helix and β-sheets (mostly stabilized by H-bonds) Tertiary: the 3-D arrangement of all amino acids in a folded single polypeptide chain (mostly stabilized by H-bonds, hydrophobic interactions, ionic bonds and disulfide bridge) Quaternary: the spatial relationship among different polypeptide chains  assembled subunits Prepared by SWT 2024 email: [email protected] 18 Intermolecular forces in proteins Hydrogen bonds Hydrophobic interactions Ionic or electrostatic bonds Disulfide bridges https://img.brainkart.com/article/article-Forces-Involved-in-T-ytL.jpg Prepared by SWT 2024 email: [email protected] 19 Biological functions of proteins Proteins are naturally occurring polypeptides They perform a wide range of biological functions Enzymatic catalysis Transport and storage Mechanical functions Movement Protection Information processing Prepared by SWT 2024 email: [email protected] 20 Big 4 macromolecules – (2) Carbohydrates Carbohydrates 碳水化合物 are compounds composed of carbon (C), hydrogen (H) and oxygen (O) atoms in a ratio of 1:2:1 or with the general formula of (CH2O)n, where n refers to the number of C atoms e.g., in glucose, n = 6, so its formula is C6H12O6 Carbohydrates contain no genetic information A source of energy that can be quickly mobilized Also known as sugars Because some classes of carbohydrates give a sweet taste Synthesized by photosynthesis in plants Prepared by SWT 2024 email: [email protected] 21 Classification of carbohydrates Monosaccharides 單醣 (simple sugars) Cannot be broken down further into simpler sugars e.g., Glucose 葡萄糖, galactose 半乳糖, fructose 果糖 Disaccharides 2 monosaccharides linked together through glycosidic bonds e.g., Maltose, lactose and sucrose Oligosaccharides 寡糖 (oligo = "a few“) 3 to 10 monosaccharides linked together through glycosidic bonds Polysaccharides 多醣 Polymers of monosaccharides e.g., Starch 澱粉, cellulose 纖維素 and glycogen 糖原 Prepared by SWT 2024 email: [email protected] 22 Monosaccharides Prime example: glucose Building block for di- and poly-saccharides Known as blood sugar in the human body Normal blood glucose level: 70-99 mg per 100 mL blood (mg/dL) The most important simple carbohydrate in human metabolism 蔗糖 glucose glucose 葡萄糖 maltose 麥芽糖 Prepared by SWT 2024 email: [email protected] 23 Polysaccharides The 3 polysaccharides of interest to human are glycogen, starch and cellulose Glycogen is an energy-storage polysaccharide made by cells of the liver, muscles, brain, uterus and vagina Starch is the corresponding energy-storage polysaccharide of plants, a significant digestible polysaccharide in the human diet Cellulose is a structural polysaccharide that gives strength to the cell walls of plants, yet humans have no enzymes to digest it Prepared by SWT 2024 email: [email protected] 24 Biological functions of carbohydrates Carbohydrates are polymers of monosaccharides that are linked by glycosidic bonds Carbohydrates serve as Energy stores Fuels Metabolic intermediates Structural elements of DNA, RNA and cells Prepared by SWT 2024 email: [email protected] 25 Big 4 macromolecules – (3) Lipids Usually composed only of carbon, hydrogen and oxygen atoms; mainly made of hydrocarbon chains Insoluble in water since most of the carbon and hydrogen atoms are linked by nonpolar covalent bonds (i.e., hydrophobic organic molecules) Lipids contain no genetic information Can be used as energy storage and heat insulation Less oxidized than carbohydrates, thus have more calories per gram Five primary types of lipids in humans: fatty acids 脂肪酸, triglycerides 甘油 三酸酯, phospholipids 磷脂, eicosanoids 類二十烷酸 and steroids 類固醇 Prepared by SWT 2024 email: [email protected] 26 i. Fatty acids Fatty acid is a chain of carbon atoms (usually 4 to 24) with a carboxyl group 羧基 at one end and a methyl group 甲基 at the other either saturated or unsaturated Most fatty acids can be synthesized by the human body, but a few called essential fatty acids must be obtained from the diet because we cannot synthesize them Prepared by SWT 2024 email: [email protected] 27  ii. Triglycerides 甘油三酸酯 Triglycerides are commonly known as “fats” Constructed with 2 types of smaller molecules: glycerol 甘油 + 3 fatty acids solid at room liquid at room temperature temperature plant fats and most animal fats fish fats are are saturated usually unsaturated Prepared by SWT 2024 email: [email protected] 28 ii. Triglycerides (cont’d) A diet rich in saturated fats may contribute to cardiovascular disease through plaque deposits Hydrogenation 氫化 is the process of converting unsaturated fats (cis) to saturated fats by adding hydrogen; however, trans unsaturated may be produced In unsaturated fats, double bond usually has the cis conformation Prepared by SWT 2024 email: [email protected] 29 https://www.pharmacy.nhg.com.sg/uploadedImages/Health_Advice/Healthy_Eating/Different%20types%20of%20fats.jpg http://thatfitbody.com/wp-content/uploads/2017/01/monounsaturated-fat- polyunsaturated-fat-saturated-fat-trans-fat.jpg Prepared by SWT 2024 email: [email protected] 30 iii. Phospholipids A phospholipid is formed when two fatty acids and one phosphate group are attached to glycerol The two fatty-acid tails are hydrophobic, but the phosphate group and its attachments form a hydrophilic head (i.e., amphipathic) An important molecule found in biological membranes, e.g., cell membrane 親水的 疏水的 Prepared by SWT 2024 email: [email protected] 31 iv. Eicosanoids Eicosanoids 類二十烷酸 are formed from C20 polyunsaturated fatty acids (e.g., arachidonic acid) Prime examples include prostaglandins, thromboxane, leukotrienes… Physiologically and pharmacologically active compounds Act on cells close to their site of production, and get rapidly degraded Prepared by SWT 2024 email: [email protected] 32 v. Steroids A steroid 類固醇 is a lipid with 17 of its carbon atoms arranged in 4 rings Cholesterol 膽固醇 is the “parent” steroid from which the other steroids are synthesized An important steroid presents as a component in animal cell membranes required for proper nervous system function The others include cortisol 皮質醇, aldosterone 醛固酮, progesterone 黃體酮, estrogens 雌激素, testosterones 睾丸激素, bile acids 膽汁酸 … Prepared by SWT 2024 email: [email protected] 33 v. Steroids − Cholesterol When the popular press refers to “good” and “bad” cholesterol, it is actually referring to droplets in the blood called lipoproteins 脂蛋白, which are a complex of cholesterol, fat, phospholipids and protein Bad cholesterol refers to low-density lipoprotein (LDL), which has a high ratio of lipid to protein and contributes to cardiovascular disease Good cholesterol refers to high-density lipoprotein (HDL), which has a lower ratio of lipid to protein and may help to prevent cardiovascular disease Only ~15% of our cholesterol comes from the diet, the other 85% is internally synthesized, primarily by the liver Prepared by SWT 2024 email: [email protected] 34 Big 4 macromolecules – (4) Nucleic acids Nucleic acids 核酸 are polymers of nucleotides 核苷酸, i.e., polynucleotides Each nucleotide consists of a nitrogenous base, a pentose sugar (i.e., a monosaccharide) and a phosphate group The portion of a nucleotide without the phosphate group is called a nucleoside polynucleotide Prepared by SWT 2024 email: [email protected] 35 The two common nucleic acids RNA DNA Deoxyribonucleic acid (DNA) 脫氧 核糖核酸 DNA contains a 2’-deoxyribose Ribonucleic acid (RNA) 核糖核酸 RNA contains a ribose DNA is the repository of our genes DNA directs the synthesis of messenger RNA (mRNA), which controls protein synthesis 36 Prepared by SWT 2024 email: [email protected] Nitrogenous bases Two families of nitrogenous bases Purines (adenine and guanine) have double rings Pyrimidines (cytosine, thymine and uracil) have single rings In DNA, we have A T C G In RNA, we have A U C G Pairing rule: A pairs with T ; C pairs with G Prepared by SWT 2024 email: [email protected] 37  Nucleotides – base pairing GC DNA base pair http://en.wikipedia.org/wiki/File:AT_DNA_base_pair.svg AT DNA base pair Prepared by SWT 2024 email: [email protected] 38 Nucleotides – phosphate groups book/resources/230_Structure_of_Adenosine_Triphosphate_(ATP)-01.jpg http://oerpub.github.io/epubjs-demo- Energy transfer molecules Prepared by SWT 2024 email: [email protected] 39 Polynucleotides Nucleic acids are polynucleotides Linear polymers of nucleotides formed as 5’-nucleoside monophosphates are successively added to the 3’-OH group of the preceding nucleotide Prepared by SWT 2024 email: [email protected] 40 Polynucleotides The sequence of bases along a nucleotide polymer is unique for each gene Polynucleotides are made up of nucleotides linked by the –OH group on the 3´carbon of one nucleotide and the phosphate on the 5´carbon on the next i.e., phosphodiester bond Two polynucleotides that spiral around an imaginary axis and form a double helix DNA serve as a storage materials for genetic information in all living cells, i.e., genes 41 Prepared by SWT 2024 email: [email protected] 41 Fundamental structure of DNA Prepared by SWT 2024 email: [email protected] 42 DNA structure in humans Prepared by SWT 2024 email: [email protected] 43 RNA Smaller cousins of DNA Consist of one nucleotide chain instead of double helix  single strand Interpret the code in DNA and use those instructions to synthesize proteins Three types of RNA +of+RNA+mRNA%2C+rRNA%2C+tRNA.jpg http://slideplayer.com/2490899/9/images/5/Three+types messenger RNA (mRNA) ribosomal RNA (rRNA) transfer RNA (tRNA) RNA contains uracil (U) Prepared by SWT 2024 email: [email protected] 44 Further info of the big 4 macromolecules Percentage of dry mass of each type of macro- molecule in a cell  Fats store the most energy – ~80% of the energy in the human body – ~146 ATP from a triglyceride  Proteins are less likely to be broken down to make ATP Prepared by SWT 2024 email: [email protected] 45 Macromolecules (polymers of monomers) Polymers of monosaccharides  carbohydrates Polymers of amino acids  proteins Polymers of nucleotides  nucleic acids Synthesis A dehydration synthesis 脱水 (or condensation) occurs when 2 monomers bond together through the loss of a water molecule An enzyme may accelerate the dehydration process Breakdown A hydrolysis reaction 水解 occurs when a polymer dissembles into monomers, and it is literally the reverse of the dehydration synthesis Prepared by SWT 2024 email: [email protected] 46  Macromolecules https://kahoot.it/solo/?quizId=da21c278-a5ee-4f94-8ce7- 66c8abbfec41 Kahoot! Games Carbohydrates and lipids https://kahoot.it/solo/?quizId=f7deebeb-8f67-4dae-9a5c- 91823cc13445 Prepared by SWT 2024 email: [email protected] 47 Self-test question 1 What is the base sequence of the DNA strand that would be complementary to the following single-stranded DNA molecule? 5'─GGATCTGATCCAGTCA─3' Prepared by SWT 2024 email: [email protected] 48 Self-test question 2 If a double stranded DNA has 20% of cytosine, calculate the % of adenine in such strand. Prepared by SWT 2024 email: [email protected] 49 Self-test question 3 If a double stranded DNA has 38% of adenine, calculate the % of cytosine in such strand. Prepared by SWT 2024 email: [email protected] 50 ~ The end ~ Thank you ! Prepared by SWT 2024 email: [email protected] 51