Macromolecules: introduction on structural features and most important functions

Transcription

1 Macromolecules: introduction on structural features and most important functions 1

2 Outline Atomic and molecular composition of living matter Carbohydrates Nucleobases, nucleosides, nucleotides Aminoacids Fatty Acids 2

3 Atoms in biological matter Fundamental atoms Only a few are traceable in human body: O, N, C, H, P, S. H +, Na +, K +, Cl -, Ca 2+ most frequent ions. Others (Fe, Ni, Cu) present only in limited quantities. 3

4 Molecules of Life A few fundamental molecules Water (70% of our body mass) Phosphoric acid, dissolved as phosphate ions and protons: (H 3 PO 4 HPO H + ) Simple sugars (glucose, ribose, saccarose) Nucleobases (pirimidines and purines) Nucleotides (ATP, dgtp, camp, etc.) Fatty acids and phospholipids (POPC, DPPC, etc.) Aminoacids 4

5 Carbohydrates Molecules made of C, H and O, with general formula C m (H 2 O) n H:O ratio generally equal to 2:1. Exceptions do exist, ominous one is deoxyribose in DNA, having formula C 5 H 10 O 4. Very important energy source of metabolism. More structurally complex than other macromolecules. In biochemistry they are synonymous of saccharides: Mono-, di-, oligo- and poly-saccharides 5

6 Monosaccharides (CH 2 O) n n 3 (glucose, fructose, ribose). Important source of energy (synthesis of ATP) and constituents of nucleic acids. 5 or 6-atoms ring structures with 1 oxygen. Stereochemistry: α or β. α-d-glucopyranose β-d-glucopyranose 6

7 Monosaccharides Found in nature as mixture of open and cyclic structures. 7

8 Disaccharides Dimers of monosaccharides linked by a glycosidic bond of type α or β. Glycosidic bond: between a carboydrate and a functional group (e.g. alcohol). 8

9 Disaccharides Examples are lactose, sucrose, maltose First energy stock 9

10 Oligo/polysaccharides Oligosaccharides have formula [C m (H 2 O) n ] x, x between 3 and 9. Can covalently bind to amino acids glycoproteins (lying on both membrane and cytosol) and to lipids glycolipids. Play a role in inter-cellular interactions. Polysaccharides have formula C m (H 2 O) n with m 200. Cellulose, amides, glycogen, pectin, chitin, etc. Capsules secerned by some bacteria composed of thick layers of polysaccharides enveloping antigenes. Hinder immunity response of host organism. 10

11 Oligo/polysaccharides Amide (starch): polysaccharide of glucose Fundamental stock of energy in plants. Two principal structures: 1. Amylose Linear chain with glycosidic bond α-1,4 (helicoid structure). Constitutes about 20% of amide structure. 11

12 Oligo/polysaccharides Amide (starch): polysaccharide of glucose 2. Amylopectin Features branches through glycosidic bond α-1,6. Ratios of 1,6 vs. 1,4 bonds in range 1/24-1/30. Constitutes about 80% of amide structure. 12

13 Oligo/polysaccharides Glycogen: polysaccharide of glucose Primary energy stock in animals. Structure similar to amylopectin, more branching (ratio of α-1,6 vs. α-1,4 bonds equals 1/10). Synthesized from protein glycogenin. 13

14 Oligo/polysaccharides Cellulose: polysaccharide of glucose Fundamental structure in vegetal kingdom. ~10 15 Kg of cellulose synthesized and degraded per year. Planar structure due to β-1,4 glycosidic bond, functional to build highly resistant fibers such as those found in plants. 14

15 Oligo/polysaccharides Difference between α-1,4 and β,1-4 bonds Structures built through α-1,4 bonds are willing to assume helicoidal structure. Structures built through β-1,4 bonds tend to form linear structures and to self-assemble into planar sheets linked through H-bonds. 15

16 Nucleobases, nucleosides, nucleotides Bases of nucleic acids: 5 fundamental types 2 classes: purines (2) and pirimidines (3) 16

17 Nucleobases, nucleosides, nucleotides DNA: A, G, C, T 17

18 Nucleobases, nucleosides, nucleotides RNA: A, G, C, U 18

19 Nucleobases, nucleosides, nucleotides (deoxy)nucleoside base covalently bound (glycosidic bond) to a molecule of (deoxy)ribose. Glycosilation always occurs between atom C1 of sugar and atoms N9 (purines) or N1 (pirimidines) of nucleobases

20 Nucleobases, nucleosides, nucleotides Nucleotide nucleoside bound to one or more phosphate groups. 5 o 3 depending on where substitution do occur ATP Adenosine Tri-Phosphate 3 -dgmp deoxyguanosine Mono-Phosphate 20

21 Aminoacids 21 different types of α-aminoacids in eukaryotes Same backbone, different side chains R Amine (base) Carboxyl (acid) Side chain 21

22 Aminoacids 21 different types of α-aminoacids in eukaryotes Same backbone, different side chains R Zwitterions in solution (terminal amino e carboxyl groups) Neutral Zwitterionic Amine (base) Carboxyl (acid) Side chain 22

23 Aminoacids Chiral molecules (not superimposable to their mirror image) Enantiomers Enantiomers (optical isomers) D and L All aminoacids exist in L form during translation D enantiomers generated by post-translation processes, occur in peptidoglycan, are used as neurotransmitters... 23

24 Chirality Chirality is an essential parameter for the intermolecular interactions and for processes such as molecular recognition L carvon (smells like mint) R carvon (smells like cumin) Odorant receptors contain chiral groups! 24

25 Chirality Chirality is an essential parameter for the intermolecular interactions and for processes such as molecular recognition L methorphan (analgesic) R methorphan (cough sedative) Molecules with different chirality interact in a different way (with high or low affinity) with the same receptors 25

26 Aminoacids Most are hydrophobic Aliphatic A, V, I, L, M Aromatic F, Y, W 26

27 Aminoacids Polar (ph 7.4) S, T, N, Q Charged (ph 7.4) + R, H, K - D, E 27

28 Aminoacids Special C: contains the thiol group (SH), is polar and used to form disuphilde bonds G: hydrogen as side chain (only achiral AA) P: side chain include a C-N bond (hydrophobic) 28

29 Aminoacids Several functional groups are attached to different AAs 29

30 Aminoacids Nomenclature of carbon atoms of the side chain In some cases amino group bound to β or γ carbon β/γ-aminoacids 30

31 Fatty acids Aliphatic chain of C atoms ending with carboxyl group (-COOH) Polar head and hydrophobic tail amphiphatic molecules 31

32 Fatty acids Aliphatic chain of C atoms ending with carboxyl group (-COOH) Polar head and hydrophobic tail amphiphatic molecules Aliphatic chain can be saturated (linear) or contain one or more double bonds (unsaturated carbons) conformations cis and trans 32

33 Fatty acids A few ways of naming fatty acids Common names (e.g. palmitoleic, oleic, arachidic, acid) Regular nomenclature by IUPAC: counting starts from carboxylic acid carbon, and cis-/trans- or E-/Z- notation is used when double bond encountered (e.g (9Z,12Z,15Z,18Z)-octadecatetraenoic acid) Δ x : double bonds indicated by Δ x where x is number of C atom counting from carboxylic acid. Every double bond must be specified as cis or trans (e.g. cis, cis, cis, cis-δ 9,Δ 12,Δ 15,Δ 18 -octadecatetraenoic acid) n-x or ω-x nomenclature: based on biosynthetic properties of molecules in animals. First double bond counting from methyl terminal identifies class (e.g. n-3 or ω-3). However, no further details are given, so this nomenclature is ambiguous Lipid numbers: has form C:D, where C and D are total numbers of C atoms and double bonds, respectively. Ambiguous, often comes with n-x o Δ x (e.g. 18:3, 18:3ω6, 18:3, cis,cis,cis-δ 9,Δ 12,Δ 15 ) 33

34 Some unsaturated fatty acids Common name Chemical structure Δ x C:D n x Myristoleic acid CH 3 (CH 2 ) 3 CH=CH(CH 2 ) 7 COOH cis-δ 9 14:1 n 5 Palmitoleic acid CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 7 COOH cis-δ 9 16:1 n 7 Sapienic acid CH 3 (CH 2 ) 8 CH=CH(CH 2 ) 4 COOH cis-δ 6 16:1 n 10 Oleic acid CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 7 COOH cis-δ 9 18:1 n 9 Elaidic acid CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 7 COOH trans-δ 9 18:1 n 9 Vaccenic acid CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 9 COOH trans-δ 11 18:1 n 7 Linoleic acid CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 COOH cis,cis-δ 9,Δ 12 18:2 n 6 Linoelaidic acid CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 COOH trans,trans-δ 9,Δ 12 18:2 n 6 α-linolenic acid CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 7 COOH cis,cis,cis-δ 9,Δ 12,Δ 15 18:3 n 3 Arachidonic acid CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 3 COOH cis,cis,cis,cis-δ 5 Δ 8,Δ 11,Δ 14 20:4 n 6 Eicosapentaenoic acid CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 3 COOH cis,cis,cis,cis,cis- Δ 5,Δ 8,Δ 11,Δ 14,Δ 17 20:5 n 3! Erucic acid CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 11 COOH cis-δ 13 22:1 n 9 Docosahexaenoic acid CH 3 CH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CHCH 2 CH=CH(CH 2 ) 2 COOH cis,cis,cis,cis,cis,cis- Δ 4,Δ 7,Δ 10,Δ 13,Δ 16,Δ 19 22:6 n 3 34

35 Some saturated fatty acids 35

36 Fatty acids Fundamental for energy storage. Components of multi-glycerides and phospholipids. Natural fatty acids generally have even number of C atoms (4-28). Essential fatty acids: animals must assume them from external sources (food) since not able to synthetize them. Examples are ω-3 and ω-6. α-linolenic acid (ω-3) Linoleic acid (ω-6) 36

37 Most common fatty acids Short chain (C:D 4:0/6:0) Fatty acids from cow milk and derivatives Butyric acid Esanoic acid Medium chain (C:D 8:0/14:0) Tropical oils (coconut, palm) Lauric acid (C12:0) (industrial word: vegetal oil) Myristic acid (C14:0) Long chain (C:D C16) Animal and vegetal fatty acids Palmitic acid (C16:0) Stearic acid (C18:0) 37

38 Most common fatty acids Long chain (C:D C16) Oleic acid and cis-9-octadecenoic acid (18:Δ 9 ) Most abundant fatty acid in animal and vegetal fat. Typical of olive oil (where constitutes about 80% of all fatty acids). Essential fatty acids: linoleic, α-linolenic Precursors of long chain poly-unsaturated acids of classes n-6 (ω6) and n-3 (ω3) respectively. E.g. eicosapentaenoic acid (ω3) in fish oil. 38

39 Glycerides Also called acyl-glyceroles, they are esters formed by glycerol and one to three fatty acids (mono-, di-, tri-glicerides) Glycerol (alchool) Monoglyceride Diglyceride Triglyceride 39

40 Glycerides Mono and di-glyceride are said partial since not all of hydroxyl groups are esterified. Short partial glycerides are strongly polar. Used as excipients to increase solubility of drugs. Used as emulsion enhancers in food industry. Triglycerides are contained in both animal and vegetal fats. Components of skin oils. Present in blood, help bidirectional transfer of adipose fat and glucose from liver. 40

41 Phospholipids Subclass of lipids, generally formed by a 1,2-diglyceride (glycerophospholipids or phosphoglycerides), a phosphate group (at 3) and a alcohol (e.g. choline) Polar head Negative group Hydrophobic tail Amphiphatic 41

42 Glycerophospholipids Principal components of membranes of all living organisms Phosphatidic Acid (PA) -1 net charge. Precursor of biosynthesis of several other lipids. Influences curvature of phospholipid membrane. Transmitter of signals that drive recruitment of cytosolic proteins towards appropriate cellular membrane. 42

43 Glycerophospholipids Principal components of membranes of all living organisms Phosphatidil Ethanolamine (PE) Principal component of bacterial membranes. 25% of all phospholipids in cellular membranes. Generally coupled to a saturated and an unsaturated fatty acid (e.g. 1-Palmitoyl-2-oleoyl-sn-glycero -3-phosphoethanolamine, POPE). Mainly found in inner leaflet. Modulates membrane curvature. 43

44 Glycerophospholipids Principal components of membranes of all living organisms Phosphatidil Choline (PC) Principal component of membranes in animals. Generally coupled to a saturated and a unsaturated fatty acid (e.g. 1-Palmitoyl-2-oleoyl-sn-glycero -3-phosphocholine, POPC). Mainly present in outer leaflet of membrane. Absent in almost all bacteria. 44

45 Glycerophospholipids Principal components of membranes of all living organisms Phosphatidil Serine (PS) Anionic at physioligical ph. Role in cell-signaling: - In normal conditions kept within inner leaflet by flippases (other phospholipids free to change their orientation). - During cellular apoptosis flippase stops its activity, and PS is found also on outer leaflet, which is a signal to macrophages. 45

46 Glycerophospholipids Principal components of membranes of all living organisms Phosphatidil Glycerol (PG) Anionic at physiological ph. Found in almost all bacteria (e.g. 20% of membranes in E. coli). Building block of cardiolipin, constitutive molecule of inner mitochondrial membrane. 46

47 Sphingolipids A.k.a. glycosilceramides: second most important class of lipids Contain sphingoids, an ensemble of amino-alcohol bases among which the most frequent is sphingosin 47

48 Glycolipids Lipids bound to a carbohydrate. Depending on intermediate group classified as glyco (H), glycero-glyco (glycerol) and sphingo-glyco (sphingosin) lipids Energy source Signaling (carbohydrates on outer membranes in eukaryotes) Involved in inter-cellular adhesion and building of tissues 48

49 Sterols Derivatives of sterol polycyclic compound bearing four condensed rings (three exa- and one penta-ring). C 17 D 3 A B Alcoholic group bound to 3 in A, remaining aromatic amphiphatic lipids Aliphatic chain branching off from C17 of ring D (precursors of steroids) Subclass of steroids (also called alcohol-steroids) 49

50 Cholesterol Most important sterol synthetized by animals Structural block of all animal membranes, where inserts between two layers of phospholipids with OH group close to polar heads. Key to structural integrity and fluidity of membrane. Contributes to reduce permeability of small hydro-soluble molecules. Key component of cellular (synaptic) vesicles (many synaptic proteins bind to it). Precursor of steroids hormones (e.g. cortisone and testosterone) and vitamin D. 50