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Biological Molecules Dr Daniel N. Meijles Senior Lecturer in Cardiovascular Biology [email protected] MPharm lecture series Biological molecules on earth • Life is based on reactions between molecules • Biological molecules are carbon-based (except for some small inorganic molecules) • Biologi...

Biological Molecules Dr Daniel N. Meijles Senior Lecturer in Cardiovascular Biology [email protected] MPharm lecture series Biological molecules on earth • Life is based on reactions between molecules • Biological molecules are carbon-based (except for some small inorganic molecules) • Biological molecules can be classified into a small number of categories, each has small and large molecules A summary of biological molecules Small (Mw=100-1000, ~30 Catoms) sugars amino acids nucleotides lipids/fats Large (macromolecules) polysaccharides proteins nucleic acids (DNA, RNA) associate to form membranes Small molecules often play at least two roles: • as building blocks for macromolecules • as some other specific function in their own right Composition of the cell… water inorganic ions small organic molecules macromolecules proportion of total cell weight (%) 70 1 3 26 A summary of biological molecules Small (Mw=100-1000, ~30 Catoms) sugars amino acids nucleotides lipids/fats Large (macromolecules) polysaccharides proteins nucleic acids (DNA, RNA) associate to form membranes Small molecules often play at least two roles: • as building blocks for macromolecules • as some other specific function in their own right Carbohydrates • General formula: (CH2O)n • Most common organic compound on earth. • Function as energy storage, fuel, metabolite, and structural element Monosaccharides • All have the formula (CH2O)n • Two kinds of monosaccharides: 1) Ketone based → ketose 2) Aldehyde based → aldose • Number of C-atoms determines name: ▫ triose, tetrose, pentose, hexose, heptose • They have chiral centres  enantionmers Example one: Glucose • An aldose • 6 C-atoms: hexose • D-configuration: asymmetric C-atom most distant from the aldehyde/ketone group • Can exist in longchain and ring structure Long-chain structure α-D-Glucopyranose Ring structure (hemiacetal) D-Glucose β-DGlucofuranose Disaccharides α-D-glucose with β-D-fructose H2O is released upon bond formation: Condensation reaction β-D-galactose with α-D-glucose Polysaccharides β-1-4 glycosidic bond α-1-4 glycosidic bond Example two: Glycogen • An aldose • 6 C-atoms: hexose Oligosaccharides: e.g. blood groups Example three: ABO groups A summary of biological molecules Small (Mw=100-1000, ~30 Catoms) sugars amino acids nucleotides lipids/fats Large (macromolecules) polysaccharides proteins nucleic acids (DNA, RNA) associate to form membranes Small molecules often play at least two roles: • as building blocks for macromolecules • as some other specific function in their own right Amino acids – protein building blocks amine group carboxyl acid group R = rest, 20 or more variations of amino acid “side chain” Amino acids react to form peptides Structure of proteins Primary structure Covalent bonds forming polymer – e.g. order of amino acid residues joined by peptide bonds Secondary structure Regular folded form, often stabilised by hydrogen bonds – e.g. helices and sheets Tertiary structure Overall 3D structure, stabilised by hydrogen bonds, hydrophobic, hydrophilic and Van der Waal’s forces Quaternary structure Organisation of macromolecules into assemblies, often stabilised by ionic bonds – several polypeptide chains can make up a protein e.g. Amino acids: building blocks and more… Triggers glycogen breakdown Tyrosine Adrenaline Vasodilator Histidine Histamine A summary of biological molecules Small (Mw=100-1000, ~30 Catoms) sugars amino acids nucleotides lipids/fats Large (macromolecules) polysaccharides proteins nucleic acids (DNA, RNA) associate to form membranes Small molecules often play at least two roles: • as building blocks for macromolecules • as some other specific function in their own right Nucleotides: sugar, base & phosphate 5’ 3’ 2’-deoxy Nucleotides: sugar-phosphate binding Double stranded DNA Nucleotides: building blocks and more… Energy unit Second messenger Involved in RNA synthesis A summary of biological molecules Small (Mw=100-1000, ~30 Catoms) sugars amino acids nucleotides lipids/fats Large (macromolecules) polysaccharides proteins nucleic acids (DNA, RNA) associate to form membranes Small molecules often play at least two roles: • as building blocks for macromolecules • as some other specific function in their own right Body fats • Act predominantly as food reserves (i.e. for energy) • Are glycerol esters of fatty acids Glycerol Triglycerides ester bond Phospholipids Lipids form membranes Phospholipid bilayer Cholesterol • Cholesterol is a steroid • It can intercalate into the membrane: a) OH group interact with the polar lipid heads b) its steroid scaffold interact with the fatty acids • Decreases fluidity and increases flexibility of the membrane • Reduces permeability for soluble molecules Cholesterol as a hormone building block Cholesterol Structure and function relationships • Proteins that denature (loss of structure) or are mutated (change structure) affect function • Starch and glycogen are major energy sources for humans, whereas we cannot digest cellulose (different glucose polymer) • Single oxygen difference makes DNA much more stable than RNA Example single molecule diseases • Diabetes (insulin-dependent) absence of a protein hormone (insulin) leads to failure to regulate blood glucose • Sickle cell disease one amino acid change in a globin chain causes haemoglobin to aggregate into polymers • Cystic fibrosis absence of a membrane protein that transports chloride leads to altered properties of secretions Biological molecules: recommended reading L. Stryer (2015) Biochemistry (8th edition), WH Freeman Dr Daniel N. Meijles [email protected]

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