macromolecules: introduction on structural features and ... · macromolecules: introduction on...

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.

Macromolecules: introduction on structural

features and most important functions

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Outline

•  Atomic and molecular composition of living matter

•  Carbohydrates

•  Nucleobases, nucleosides, nucleotides

•  Aminoacids

•  Fatty Acids

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Atoms in biological matter

Fundamental atoms

•  Only a few are traceable in human body: O, N, C, H, P, S.

•  H+, Na+, K+, Cl-, Ca2+ most frequent ions.

•  Others (Fe, Ni, Cu) present only in limited quantities.

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Molecules of Life A few fundamental molecules

•  Water (70% of our body mass)

•  Phosphoric acid, dissolved as phosphate ions and protons: (H3PO4 ⇔ HPO4

2- + 2H+)

•  Simple sugars (glucose, ribose, saccarose)

•  Nucleobases (pirimidines and purines)

•  Nucleotides (ATP, dGTP, cAMP, etc.)

•  Fatty acids and phospholipids (POPC, DPPC, etc.)

•  Aminoacids

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Carbohydrates • Molecules made of C, H and O, with general formula

Cm(H2O)n H:O ratio generally equal to 2:1.

– Exceptions do exist, ominous one is deoxyribose in DNA, having formula C5H10O4.

•  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

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Monosaccharides

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•  (CH2O)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


Monosaccharides

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•  Found in nature as mixture of open and cyclic structures.


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).

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Disaccharides •  Examples are lactose, sucrose, maltose

•  First energy stock

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Oligo/polysaccharides •  Oligosaccharides have formula [Cm(H2O)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 Cm(H2O)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.

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Oligo/polysaccharides Amide (starch): polysaccharide of glucose

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1. Amylose

•  Linear chain with glycosidic bond α-1,4 (helicoid structure).

•  Constitutes about 20% of amide structure.

•  Fundamental stock of energy in plants.

•  Two principal structures:


Oligo/polysaccharides

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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.

Amide (starch): polysaccharide of glucose


Oligo/polysaccharides Glycogen: polysaccharide of glucose

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•  Structure similar to amylopectin, more branching (ratio of α-1,6 vs. α-1,4 bonds equals 1/10).

•  Primary energy stock in animals.

•  Synthesized from protein glycogenin.


Oligo/polysaccharides

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•  Fundamental structure in vegetal kingdom.

•  ~1015 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.

Cellulose: polysaccharide of glucose


Oligo/polysaccharides Difference between α-1,4 and β,1-4 bonds

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•  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.


Nucleobases, nucleosides, nucleotides •  Bases of nucleic acids: 5 fundamental types

•  2 classes: purines (2) and pirimidines (3)

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and pirimidines (3)


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

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

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Nucleobases, nucleosides, nucleotides

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•  (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.

1’ 3’

5’


Nucleobases, nucleosides, nucleotides •  Nucleotide nucleoside bound to one or more phosphate groups.

•  5’ o 3’ depending on where substitution do occur.

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1’ 3’

5’

3’

5’

3’

5’

5’-ATP Adenosine Tri-Phosphate

3’-dGMP deoxyGuanosine Mono-Phosphate


Aminoacids

•  21 different types of α-aminoacids in eukaryotes

•  Same backbone, different side chains R

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Carboxyl (acid)

Amine (base)

Side chain


Aminoacids

•  21 different types of α-aminoacids in eukaryotes

•  Same backbone, different side chains R

•  Zwitterions in solution (terminal amino e carboxyl groups)

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Zwitterionic Neutral

Carboxyl (acid)

Amine (base)

Side chain


Aminoacids Chiral molecules (not superimposable to their mirror image)

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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...


Chirality

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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!


Chirality

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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

Chirality is an essential parameter for the intermolecular interactions and for processes such as molecular recognition


Aminoacids Most are hydrophobic

•  Aliphatic A, V, I, L, M

•  Aromatic F, Y, W

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Aminoacids

Polar (pH 7.4) S, T, N, Q

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Charged (pH 7.4)

+ R, H, K

- D, E


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)

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Aminoacids Several functional groups are attached to different AAs

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Aminoacids Nomenclature of carbon atoms of the side chain

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In some cases amino group bound to β or γ carbon

β/γ-aminoacids


Fatty acids Aliphatic chain of C atoms ending with carboxyl group (-COOH)

•  Polar head and hydrophobic tail amphiphatic molecules

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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

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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)

–  Δx: double bonds indicated by Δx 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-Δ9,Δ12,Δ15,Δ18-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 Δx

(e.g. 18:3, 18:3ω6, 18:3, cis,cis,cis-Δ9,Δ12,Δ15)

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Some unsaturated fatty acids

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Common name Chemical structure Δx C:D n−x

Myristoleic acid CH3(CH2)3CH=CH(CH2)7COOH cis-Δ9 14:1 n−5

Palmitoleic acid CH3(CH2)5CH=CH(CH2)7COOH cis-Δ9 16:1 n−7

Sapienic acid CH3(CH2)8CH=CH(CH2)4COOH cis-Δ6 16:1 n−10

Oleic acid CH3(CH2)7CH=CH(CH2)7COOH cis-Δ9 18:1 n−9

Elaidic acid CH3(CH2)7CH=CH(CH2)7COOH trans-Δ9 18:1 n−9

Vaccenic acid CH3(CH2)5CH=CH(CH2)9COOH trans-Δ11 18:1 n−7

Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH cis,cis-Δ9,Δ12 18:2 n−6

Linoelaidic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH trans,trans-Δ9,Δ12 18:2 n−6

α-Linolenic acid CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH cis,cis,cis-Δ9,Δ12,Δ15 18:3 n−3

Arachidonic acid CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH cis,cis,cis,cis-Δ5Δ8,Δ11,Δ14 20:4 n−6

Eicosapentaenoic acid CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH cis,cis,cis,cis,cis-

Δ5,Δ8,Δ11,Δ14,Δ17 20:5 n−3

Erucic acid CH3(CH2)7CH=CH(CH2)11COOH cis-Δ13 22:1 n−9

Docosahexaenoic acid CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)2COOH cis,cis,cis,cis,cis,cis-

Δ4,Δ7,Δ10,Δ13,Δ16,Δ19 22:6 n−3


Some saturated fatty acids

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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.

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α-linolenic acid (ω-3) Linoleic acid (ω-6)


Most common fatty acids

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•  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)


Most common fatty acids

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•  Long chain (C:D ≥ C16)

•  Oleic acid and cis-9-octadecenoic acid (18:Δ9) •  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.


Glycerides

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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


Glycerides

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•  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.


Phospholipids

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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


Glycerophospholipids

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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.



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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.




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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.




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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.




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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.



Sphingolipids

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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


Glycolipids

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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


Sterols

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Derivatives of sterol polycyclic compound bearing four condensed rings (three exa- and one penta-ring).

A B

C D

3

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•  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)


Cholesterol

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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.

macromolecules: introduction on structural features and ... · macromolecules: introduction on...

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