Biology: Macromolecules and Polymers

- Electrons are not always shared equally and are closer to one atom than the other.
- Polar vs. Nonpolar
- Dipole moment

- Polar molecules contain O,N,S,P
- Nonpolar molecules contain C,H

- measure of seperation of electrical charge
- has a magnitude and direction

- Different eukaryotic cells have the same organelles
- differ in number, shape and distribution of organelles

- Eukaryotic cell cytoplasm is a crowded compartment
- Cytoplasm = organelles + cytosol

- Much of what we know about cell biology comes from cultured cells
- Cells from Henrietta Lacks (HeLa) have been cultured since 1951

- Atoms are held together by bonds
- Covalent and Noncovalent bonds

- Sharing of electrons
- Polar vs Nonpolar
- Strong (stronger than thermal energies of random collisions)
- keep organic molecules together
- broken using enzymes
- Energy is stored in bonds and breaking bonds can release energy for useful work
- need a "just right" attraction ex. If molecules are too close repelling will take place

- relatively weak
- not sharing of electrons, but attractive forces between atoms
- imp. for folding macromolecules into proper shape (e.g., enzymes)
- imp. for holding molecules together
- electrostatic attraction

- attractions between molecules with polar, covalent bonds can form complementary charges
- relatively weak and easily break and reform
- although weak, many together can be strong (think of Velcro®)

1. Ionic bonds*
2. Hydrogen bonds
3. van der Waals attractions*
4. Hydrophobic force*

- Between bonded electronegative atom and bonded H atom
H is “sandwiched” between two electron-attracting atoms
- H bonds form between most polar molecules and are especially important in the behavior of water.
- Partial charges between molecules attract each other and from hydrogen bonds.
- Hydrogen bonds stabilize adjacent molecules to form arrays or crystals, e.g., water, or stabilize 3 dimensional configurations of large molecules, e.g., proteins.

- most cellular structures (e.g., ribosomes, chromosomes, membranes) are made up by linear molecules (macromolecules)

monomers and polymers
- Lipids are macromolecules, but not polymers
- Condenstation vs Hydrolysis

1. Carbohydrates (monosaccharides)
2. Lipids
3. Nucleic acids (nucleotides)
4. Proteins (amino acids)

- Carbohydrates (monosaccharides)
- Nucleic acids (nucleotides)
- Proteins (amino acids)

Forms:
- monosaccharides (monomer)
- oligosaccharides (short polymer; 3–10 sugars)
- polysaccharides (long polymer)
Functions:
- chemical energy stored in covalent bonds is primary source of cell energy
- sugar polymers are the most abundant structural components on earth

Glucose is a key molecule in the metabolism of plants and animals

- 2 sugar units
- ex. Lactose (milk sugar) glucose + galactose

in between disaccharides
- covalent bond

- many sugar units
- imp. for energy storage and cell structure
- storange vs structural polysacride

Forms: (diverse structures; all mostly hydrophobic)
-fats
-steroids (sterols)
-phospholipids
Functions:
-energy storage (2X as much as carbohydrates).
-membrane structure
-specific biological functions

- CH2 (carboxyl) - non poplar molecules
- storage form of energy - carbons are broken off
- Glycerol + Fatty acid = triacylglycerol
- 3 fatty acids esterified (combined to an alchol or alchol combined to acid) to glycerol
- Storage form of fat in plants and animals

- saturated vs. unsaturated
- amphipathic (polar/nonpolar) one end hydrophilic the other hydrophobic
- size (usually even & 14 to 20 carbons)
- one hydrogen (double bond) - forms a kink

- double bonds make kinks
- the more double bonds the more liquid at RT
- animal fats tend to be saturated
- plants fats tend to be unsaturated and liquid (oil)
- hydrogenate vegetable fat to make solid margarine
- Storage form in plants & animals

- lower temperature it will freeze
- temp goes up will eventually become liquid

- glycerol + 2 fatty acids + phosphate group bound to a polar group
- amphipathic and make up the backbone of cell membranes
- some are kink and some are straight - changes the fluid of the membrane
- third carbon is bonded to a phosphate and something else (in this case a choline group)
- This phosphate group is very hydrophilic (has a very hydrophilic and very hydrophobic side) - important in the formation of the plasma membrane

- characteristic 4 ring structure
- cholesterol:
** membrane component
** hormone precursor (non perscription hormones)

- experiance condensation rxns
DNA - transmission of genetic info
RNA - structural and catalytic job
Forms:
- nucleotides (monomers)
- nucleic acids (polymers)--RNA and DNA
Functions:
- storage and transmission of genetic info
- structure
- catalytic

- nucleic acid monomers (Building Blocks to make polynucleotide)
- Bond breaks by the phosphate which is the energy source for forming the nucleotide
- 2 types of sugars: Deoxyribose & Ribose
- #2 prime Carbon - OH group different in DNA (DEOXY) H (store house information - 2 daughter cells exact same copy of genes **needs to be stable versus RNA (OH) (does not have to be as stable)
- RNA does not use U; looks very similar to thymine but NO methyl group
- Purines and Pyrimidnes

Purines: have two rings
Pyrimidines: single ring

- template for protein production
- template for daughter cell genome
- Two chains of DNA molecules can H-bond to form DNA double-helix
- some regions code for polypeptides
- template for protein production and daughter cells
- the nucleotides could hydrogen bond to another nucleotide of the strands

- Although RNAs generally consist of single strands, they can fold back on themselves to form double-stranded segments
- There are double-stranded RNA viruses
- RNA - does not have a double helix like DNA - more complex structure — in some region sit folds back on themselves (the structure is important to its function!!) - mutation will lead to a different shape —— bad FUNCTION
- RNA come together in the cytoplasm to make a protein

RNA functions
1. genetic information and transmission - (virus)
2. catalytic enzymes (activation energy not broken down as part of the rxn) -- ribozymes (RNA ENZYMES) — example. peptransferace ** a ribosome RNA NOT A PROTEIN
3. structure -- ribosome structure

Forms:
- polymers of 20 different AA (amino acids) in genome
- unique arrangement of AA gives protein unique shapes allowing selective interactions
- Typical cell may have 10,000 different proteins
Functions:
- Molecular tools and machines that perform nearly all the cell’s activities

- Reaction occurs on ribosomes in the cell
- protein + amino acid --> protein (w energy from nucleoside triphospahate hydrolysis)

- average = 100 amino acids long
- shape and structure of polypeptide at different levels
1. Primary Structure
2. Secondary Structure
3. Tertiary Structure
4. Quaternary Structure

e.g., Arg-Gly-Asp-Ser (RGDS)
- precise order of AA determined by genes
- sequence determines protein shape
- held together by peptide bonds
- Changes in amino acid sequence caused by changes (mutations) in DNA
- Average protein in human genome contains ~100 aa
- Order of amino acids: (the sequence of the polypeptide) - in the DNA there is a series of nucleotides and the genes determine the order - changes the shape which changes the function
- Held together by peptide covalent bonds
- MUTATION = CHANGE = WRONG AMINO ACIDS ** change in the primary structure

- Once part of a polypeptide, an individual amino acid is called a residue
- Side chains (aka R groups) give each AA its unique properties
- Some side chains are nonpolar and some are neg or pos uncharged polar
- R chains could be hydrophilic or hydrophobic
- DO NOT have to know abbreviations
- hydrophobic (center of protein - away from water)
- If charged, could bond to water - they are polar
- If not charged, but polar bonds they will have hydrogen bonds
- Non polar - on the INSIDE of the protein
- Lots of hydrophll or phobic in a row will change the hold of the protein

- side chains are not part of peptide bonds
- even though the backbone amino and carboxyl are polar, the H- bond with each other and not with
- water, so the properties of the R-groups determines the hydrophobicity of the polypeptide

- describes conformation (spatial organization) of polypeptide chain portions
- formed between N-H and C=O of polypeptide backbone and doesn’t involve R-groups. Thus can be formed by many AA sequences (the identities of the R-groups, however, puts constraints on which type of conformations can form)
- preferred ones provide maximum possible number of H–bonds between neighboring AA
- there are two common conformations found in many proteins -- alpha(α) helix and beta (Ω) pleated-sheet

- cylindrical, twisting spiral
- H-bonds between AA of same molecule
- peptide bonds of
every 4th aa close
- H-bonds parallel to cylinder axis
- R-groups to outside
- α-helices can cross lipid bilayer
e.g., wool protein; can be stretched

- hydrogen bonds keep it together
- hydrogen bonding (hydrogen in positively charged)
- hydrogen bonds are parallel t the axis of the helix
- 3.6 residues
- could be embedded in hydrophobic lipid bilayer (takes 22 amino acids to make through)

- Sometimes 2-3 α-helices wrap around each other
- Intertwined
α helices can
form a coiled- coil
- Heptad (7 aa repeat)
~ every 4th aa is hydrophobic and so a stripe of hydrophobic on inner surface
- attract together bc they are repelled from water — more energetically stable

- several polypeptide segments lie side-by-side; adopt folded or pleated conformation
- H bonds perpendicular to molecule axis
- In some regions there could be hydrogen bonding between CO & O2
- If it could be strengthen - it would not, because you are breaking covalent bonds ex. why silk wont stretch
e.g., silk protein; can’t be stretched

- In the average polypeptide, 60% of the chain is α-helix or �- sheet
- Chain portions not organized into α-helix or
�-pleated sheet may
consist of hinges, turns, loops
- often most flexible portions of chain & sites of greatest biological activity

- Makes up the conformation of the entire protein
- noncovalent interactions between R groups in same chain
- Fibrous proteins (highly elongated shape - more stretched out) - long strands or flattened sheets that resist pulling
- Globular proteins (shaped like a ball) – most proteins in the cell; compact shape; chains folded & twisted into
- complex shapes

- Noncovalent interactions between R groups in same polypeptide chain (VDW and hydrogen bonds)
Disulfide (—SS—) bridge:
- cysteine (—SH) group often covalently linked to another cysteine
- helps stabilize protein structure - once it is formed these covalent bonds are added to help STABILIZE
- oxidation and reduction
- 1 bond that is covalent: disulfide
ex. hair perm: breaks down disulfide to put hair in a certain shape

- Protein folding is inherent in the molecule
- may be sped up by accessory proteins
a. Denaturation and rentuaration of rbonuclease
b. Synthesis and self-assembly of ribonuclease
ex. take cow protein - you could change shape and ph to make it stretched out — back to same — back to original conditions

- the linking of polypeptide chains to form multisubunit functional protein (e.g., dimer, trimer or tetramer)
- intermolecular R group interactions
subunits synthesized separately
- may be linked by disulfide bonds, but more often noncovalent bonds
- Molecular chaperones
Note: quaternary structure DOES NOT mean four subunits

- Many proteins do not have the quaternary structure - a dimer
- alpha and beta come together to create a dimer, it functions as a dimer. Meaning, when the alpha and beta are separate they do not have a function; when they are together they do!
- Contains 2,3,4,5 subunits quit DOES NOT MEAN 4; our example just shows that
- R group interaction between polypeptides
- disulfide bonds (covalent interactions holding together)

- not all proteins assume proper tertiary or quaternary structure by self-assembly
- interactions with other proteins may inhibit correct folding
- chaperones help unfolded/misfolded proteins
- When proteins are being synthesized. a lot of times they have things helping them out: chaperones
- Endoplasmic Retic: most of the proteins within the ER or cytoplasm help the protein fold correctly (need ATP for this interaction); shield them from the cytoplasm
- Temperature effects protein folding
- too many misfiled proteins - cell will stop producing protein - increasing chaperone proteins so that proteins can finally be folded in the correct way

- Polypeptides --chains of AA
- Proteins -- one or more polypeptides folded into a specific conformation; a functional molecule
- enzyme is a protein, but to unfold the protein and not in its functional form it is called a polypeptide

- (level of organization distinct from primary to quaternary; sometimes called “supersecondary structure”)
- proteins often composed of 2 or more distinct modules (domains) that fold independently of one another (structurally or functionally)
- often represent parts that function in semi-independent manner
- part of a protein sequence that can function, evolve and exist independently of the rest of the protein chain
- usually 25-500 AA in length

- It would still have its same shape
Domains: its own little region folding on its own
- protein molecule could be made up of two differnt domains

- DOMAINS
- part of a protein sequence that can function, evolve and exist independently of the rest of the protein chain
- usually 25-500 AA in length
- multi-domain proteins probably evolved by the fusion of genes that once encoded separate proteins

- Many times the activity of proteins is controlled by altering the shape of the protein
- Most proteins are allosteric; can adopt 2 or
more conformations, which is regulated by something binding to its non- active site
- If a cell could change the shape of the protein - it could change its function
allosteric: changing the shape in order to bind to the enzyme

regulates the activity of this hypothetical enzyme
- ADP can only bind to closed conformation
- Closed protein now more likely to bind substrat

- can regulate protein activity
- cell signaling - surface of the cell causes shape change to the protein of the cell

- This shows a polypeptide folded in its tertiary shape — it is going left to right (showing a SHAPE CHANGE) — adding a phosphate covalently to change the shape of the polypeptide protein
Kinase: are specific; need specific phosphate in a certain way to change the shape of the polypeptide
- Phophtase: an enzyme that takes off phosphate to revert back to original condition (shown in the right image)
Changing the sequence is CHANGING the shape

Many GTP-binding proteins can be switched on/off by a gain/loss of a phosphate group
- different between GTP and GDP - this is not a phosphorylation, this is a binding site that activates and inactivates
example of this is: vision (photons binding and G-proteins changes shape and ions temporarily — vision is very quick) — rapid change by changing the charge
- Large conformational change protein synthesis enlongation factor releases tRNA when GTP to GDP

- Large conformational change protein synthesis enlongation factor releases tRNA when GTP to GDP
- During Protein Synthesis: G Protein binds to GTP and GDP to make different shape and activity
- When GTP to GDP tRNA is release with the change of shape, meaning 2-3 phosphates could make a large difference in the shape of the protein
- Elongations: 20 amino acids added per second >> a fast process

- Cellular motors can use conformation change with ATP hydrolysis to move along a track