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1 MB ChB PHASE I THE MOLECULES OF LIFE LECTURE 1 AIM: To review: the elements of life; the roles of functional groups and of molecular configuration and conformation in biomolecular function; the chemical reactions of life. http://www.abdn.ac.uk/~bch118/index.htm 2 Molecular unity/simplicity biological diversity/complexity, underlie i.e. the chemistry of life is similar in all organisms. This similarity is seen at the elemental level; at the molecular level; in the kinds of reactions that occur. [Life at the Molecular Level Lecture 1] 3 ELEMENTS OF LIFE Of ~90 natural elements, ~10 H C N O Na P S Cl K Ca are structural parts of organisms, and needed in man in gramme quantities daily. ~12 other, ‘trace elements’ are needed in very small amounts, usually because they are essential parts of particular proteins, e.g. Fe in haemoglobin. [Proteins Lecture 4] In fact, >99% mass of most cells consists of H O N C. Why these in particular? 4 In general, light atoms form the strongest bonds, and these four are the lightest atoms able to make 1, 2, 3 and 4 bonds respectively. C is particularly versatile: it can form stable single bonds single and double bonds single, double and, occasionally, triple bonds with with H O, N with other C’s. This bonding capacity and versatility must underlie the evolution of combinations of these elements into biomolecules. 5 ‘FUNCTIONAL GROUPS’ DEFINE BIOMOLECULAR FUNCTION Many biomolecules can be thought of as derivatives of hydrocarbons, i.e. molecules with a C backbone, to which H atoms are attached: H ---C H H C H H C--H H’s may be replaced by ‘functional groups’, i.e. groups having particular chemical reactivity, e.g. -OH, -CHO, -C O, -C-OH, -NH2 O etc. 6 Biomolecular function depends in part on the presence of particular ‘functional groups’, e.g. epinephrine function requires the presence of hydroxyl phenyl and secondary amino groups. [C&H, p. 286] Function also depends on how the groups are arranged in space: 7 ROLES OF MOLECULAR CONFIGURATION AND CONFORMATION IN BIOMOLECULAR FUNCTION ‘Configuration’ = the fixed arrangement of atoms in a molecule. Many biomolecules arrangement C C contain the Groups on either side of the rigid double-bond cannot rotate, relative to each other. This means that two, distinct configurations can occur: X C C X C X ‘cis’ C X ‘trans’ The two can only be inter-converted by breaking and re-forming bonds. 8 This configurational difference can be important biologically: e.g. in the retina, light triggers cis-retinal trans-retinal, which then triggers a nerve impulse to the brain. Similarly, many biomolecules contain C’s that have four different groups attached. This arrangement can also occur in two, distinct configurations, because of the tetrahedral valency of C. E.g., for an amino-acid: 9 Such a C is said to be ‘asymmetric’ or ‘a chiral centre’. The two forms, L- and D-, (so-called because the two forms of glyceraldehyde rotate polarised light in opposite (laevo and dextro) directions) again are inter-convertible only by breaking and re-forming covalent bonds. Again, the configurational difference can be important biologically: e.g. only L-amino-acids occur in proteins. [Proteins Lecture 1] 10 ‘Conformation’ = the precise, detailed arrangement of atoms in a molecule. A molecule containing bonds around which atoms/groups can rotate may exist in many, different conformations. These are inter-convertible without breaking and re-forming covalent bonds (unlike different configurations). Some conformations may be more stable than others. 11 Thus, many biomolecules contain C C bonds, around which attached groups can rotate almost totally freely: although interactions of X, Y etc with other groups in the molecule may restrict rotation, and make some conformations more stable than others. 12 In summary, the presence of functional groups, and their arrangement in space produced by the configurations and conformations of a biomolecule, determine the overall ‘personality’ of the biomolecule, i.e. how it interacts with other molecules, and, hence, its function. 13 THE CHEMICAL REACTIONS OF LIFE There are five kinds. 1 Redox reactions reduction = gain of electrons oxidation = loss of electrons. Every reduction is accompanied by an oxidation (and vice-versa). oxidised X reduced Y e e reduced X oxidised Y 14 Oxidations (in isolation) are exergonic, reductions endergonic. [Life at the Molecular Level Lecture 2] In many biological redox reactions, two electrons (and two protons) are gained/lost, [‘… H atoms, with their ‘high energy’ electrons, are stripped off, 2 at a time …’ Life at the Molecular Level Lecture 2] i.e. two hydrogen atoms are transferred. Such reactions are called ‘dehydrogenations’ and are catalysed by ‘dehydrogenases’. 15 e.g. 2e 2H+ - - lactate pyruvate NAD+ NADH + H+ OCO HOCH CH3 OCO C O CH3 2e 2H+ Flow through this reaction, catalysed by lactate dehydrogenase, may be in the direction shown or be reversed, depending on cellular conditions. [Energy Transformations - Carbohydrates Lecture 4] 16 2 Reactions that cleave and form C C bonds e.g. cleavage of the food material glucose in the catabolic pathway ‘glycolysis’: glucose (6-C) fructose 1,6-bisphosphate (6-C) aldolase 3-C molecule 3-C molecule [Energy Transformations - Carbohydrates Lecture 4] 17 3 Internal rearrangements e.g., also in glycolysis, a rearrangement occurs in preparation for the aldolasecatalysed reaction: glucose 6-phosphate fructose 6-phosphate H H C C CCCC O O H H H C C CCCC O O H [Energy Transformations - Carbohydrates Lecture 4] 18 4 Group transfers e.g., also in glycolysis: fructose 6-phosphate ATP fructose 1,6-bisphosphate ADP In this reaction, in which a phosphate group is transferred, ATP dephosphorylation supplies energy input in preparation for the aldolase-catalysed reaction. [Energy Transformations - Carbohydrates Lecture 4] 19 5 Condensations and hydrolyses e.g. the monomeric sub-units of proteins, polysaccharides, and nucleic acids are all joined by condensation, and broken by hydrolysis. -X-OH H-Y- H2O H2O -X-Y- [Proteins; Energy Transformations - Carbohydrates; Storing and Using Genetic Information Lectures] 20 MB ChB PHASE I THE MOLECULES OF LIFE LECTURE 2 AIM: To review: the molecular composition of cells; the polymeric structure of [proteins], nucleic acids, carbohydrates, and lipids. [C&H, pp. 83-86, 181-182, 188, 201-203, 291-292, 395-398.] 21 THE MOLECULAR OF CELLS COMPOSITION Water and biopolymers components of cells. are major E.g. in Escherichia coli: % ~ no. of total different weight molecular species Water Proteins DNA RNA Polysaccharides Lipids Monomeric sub-units and intermediary metabolites Inorganic ions 70 15 1 6 3 2 1 3000 1 >3000 5 20 2 1 500 20 22 1 Proteins are polymers of amino-acid monomers linked by peptide bonds. [Proteins Lecture 1] 23 2 Nucleic acids are polymers of nucleotide monomers linked by 3’, 5’-phosphodiester bonds. A nucleotide = N/C-containing ‘base’ + pentose (5-C sugar) + 1 or more phosphates. There are 2 kinds of ‘base’ in nucleic acids: pyrimidines (flat, single rings) cytosine (C) thymine (T) uracil (U) purines (~ flat, double rings) adenine guanine [Learning Guide, p. (detailed structures for reference only)] (A) (G) 24 RNA contains mainly DNA mainly A G C U, A G C T. There are two pentoses in nucleic acids: D-ribose 2-deoxy D-ribose [Learning Guide, p. Note: 1 2 (in RNA) (in DNA) ] numbering of C atoms; why the latter is called ‘deoxy’. 25 A nucleoside = base + pentose. = adenine + D-ribose E.g. adenosine [Learning Guide, p. ] 26 Other nucleoside names: [Learning Guide, p. ] base D-ribose 2-deoxy D-ribose adenine guanine cytosine thymine uracil adenosine 2’-deoxyadenosine guanosine 2’-deoxyguanosine cytidine 2’-deoxycytidine (2’-deoxy)thymidine uridine Note: 1 nucleoside names are used in naming nucleotides; 2 deoxyribose is but deoxyribonucleosides are 2 -deoxy, 2’ -deoxy because in the nucleoside, the pentose C numbers change from 1-5 to 1’-5’, so that they’re different from those of the ring atoms of the base; 27 3 the anti-HIV drug AZT is a nucleoside analogue. [Tutorial 4 Question 4] Biological nucleotides are mainly nucleoside 5’-phosphates, e.g. adenosine 5’-monophosphate. [Learning Guide, p. ] 28 Abbreviations: adenosine 5’-monophosphate Similarly, = AMP. GMP, CMP, etc; and 2’-deoxyadenosine 5’-monophosphate =dAMP. Similarly, dGMP, dCMP, etc. With >1 phosphate is present, adenosine 5’-diphosphate Similarly, = ADP. ATP dADP GTP dCDP etc. 29 Nucleotide monomers are linked by 3’, 5’phosphodiester bonds. [Learning Guide, p. Note: ] 1 it is DNA (rather than RNA); 2 the 3’, 5’-phosphodiester bonds; 3 the 5’ and 3’ ends; 4 a simple way to represent the polymer. 30 A (brief) statement of the Watson-Crick model of DNA: two DNA polymers wind about a common axis to form a double-helix; [Learning Guide, p. ] the model involves: specific base complementarity; an antiparallel arrangement of the two polymers. The model is most stable when A on one polymer is opposite T on the other and G on one polymer is opposite C on the other. A and T, G and C are therefore ‘specific, complementary bases’. A and T are linked by G and C by hydrogen bonds. 2, and 3 [Water Lecture 1; Learning Guide, p. ] 31 The model is most stable when the two polymers are antiparallel (run in opposite directions). [Learning Guide, p. Note: ] 1 the antiparallel arrangement; 2 a simple way to represent it. 32 3 Polysaccharides are polymers of sugar monomers linked by glycosidic bonds. e.g. starch, glycogen are polymers of D-glucose (6-C). [Energy Transformations - Carbohydrates Lecture 1] D-glucose is: CHO HCOH OHCH HCOH HCOH CH2OH C 1 2 3 4 5 6 C’s 2-5 are all asymmetric; [Lecture 1] the arrangement around C5 makes the sugar shown D-glucose. 33 The O attached to C5 can bridge between C5 and C1, producing a cyclic form: In solution, linear and cyclic forms interconvert. The linear (but not cyclic) form has an aldehyde group, which can be oxidised in a reaction in which something else is reduced, so glucose is a ‘reducing sugar’. A polymer is formed by condensation: [Lecture 1] glucose-OH HO-glucose H2 O glucose-O-glucose 34 In glycogen and starch, the ‘LHS’ (as indicated in the previous diagram) of a glucose monomer is linked to another glucose monomer. The link locks that additional glucose in the cyclic form. When many monomers link together, all are locked, except one at the end of the polymer, which forms a ‘reducing end’. [Energy Transformations – Carbohydrates Lecture 1] 35 4 Lipids usually contain one or more long-chain carboxylic (fatty) acids e.g. CH3(CH2)14COOH, which may be ‘saturated’ (as above) or ‘unsaturated’ i.e. contain C C bonds. Triacyglycerols (triglycerides) are storage lipids consisting of three fatty acids esterified to glycerol: 3 fatty acids + H2C - OH H C - OH H2C - OH O H2C - O - C - hydrocarbon chain O HC - O - C - hydrocarbon chain O H2C - O - C - hydrocarbon chain glycerol triacylglycerol 3 H2O 36 Simple phospholipids have a similar structure, but with a ‘head group’ attached to one of the - OH’s of the glycerol: fatty acid long hydrocarbon ‘tail’ glycerol skeleton fatty acid O O - P - O – various structures O‘head group’