CH461 Exam 2

Lipid Properties

Aliphatic carbon chain attached to a carboxylic acid

They do not polymerize, but do associate to form higher order structures

Biological uses of Lipids

Membranes

Energy storage

Signalling

Fatty Acid Nomenclature (non shorthand)

Numbering starting from carboxylic acid

Greek numbering (like shapes!) -anoic acid suffix

Fatty Acid Nomenclature (Shorthand form)

(Number of Carbonds) : (Number of double bonds)

Saturated Fatty Acids Structural Properties

Have max hydrogens; no double bonds

Unsaturated Fatty Acids Structural Properties

Have cis double bonds

Special Polyunsaturated FA nomenclature

lowercase omega with the # of the first double bond (starting from the end of the carbon chain)

General rules for Fatty Acids

Even # of carbons

Non conjugated double bonds

Mostly cis in nature

Monounsat has first double bond at C9 and Polyunsat have their first at C12 or C15.

FA Weak Aqueous Forces

Van der Waals: VDWs take advantage of the induced dipole when the molecules are pushed together

Hydrophobic Effect: Free ordered H2O molecules around the FA by pushing hydrophobic parts together, burrying the hydrophobic surface.

Surface Area: The more SA, the more VDWs and HE present due to more waters being freed (makes the interaction more favorable)

FA 3D Structure

Free rotation around every bond because of sp3 carbons

Long linear form is most stable/favorable (low steric interaction)

Unsaturated FA’s have a kink in the backbone due to double bond

Monosaccharide Nomenclature

Carbon amount —> greek number prefixes

All sugars get -ose suffix

Aldo/Keto prefix

Carbohydrate Properties

Carbon chain with aldehyde or ketone w/ multiple OH groups

Can be added to macromolecules to alter hydrophobicity, charge, and polarity within a chemical system

Structural component in DNA/RNA and cells

3 Carbon Aldose — chirality

1 chiral center

Enantiomers

Mirror image molecules

D-sugar is mostly used; L-Aldo/Ketose are mostly used

Telling L- or D-confirmation

Look at the direction of lowest priority carbon’s OH group.

If on the right, it’s the D-isomer

If on the left, it’s the L-isomer

4 Carbon Aldose— chirality

2 chiral centers

Epimers

Molecules with the same everything, but different stereochemistry at a single carbon.

Aldopentose chemical structure

More carbons = more diversity due to new places for stereochemistry becoming available

3 and 4 carbon ketoses (structural properties)

Removes 1 possible chiral center

5 and 6 carbon ketoses (structural properties)

Same as Aldoses

Hemiacetal formation

Carbonyl + Hydroxyl group = hemiacetal

Nucleophilic Addition reaction

Done at pH 7 conditions:

1.A base deprotonates the hydroxyl, increasing its nucleophilicity

2.The OH (nucleophile) attacks the carbonyl carbon

3.Some acid accepts electrons due to protonation being needed to make a better electrophile

4.Ring formation occurs (C5 and C1 attach to the oxygen)

alpha-Anomer

When the —O is below the ring (Not favored 37%)

beta-Anomer

When the —O is above the ring (Favored 63%)

Why do anomers form?

When C₅ —OH attacks the planar C₁ C=O, there’s an equal chance of the electrons attacking from either side.

What can 5 and 6 carbon aldoses cyclize to form

Furanose and pyranose rings

How do monosaccharides form disaccharides?

By linking through glycosidic bonds

Glycosidic bond formation

The acetal —OH and the alcohol —OH go through a condensation rxn that removes water.

Glycosidic bond Nomenclature

alpha/beta —> The 2 carbons that form linkages (i.e.: α1—>4 linkage)

Glycosidic bond structure

Acetal containing is on the nonreducing end (Can’t be reversed via protonation/deprotonation)

Hemiacetal is on the reducing end (Can be reduced via protonation/deprotonation)

Homopolysaccharides

Same monomer repeats (can be branched/unbranched)

Heteropolysaccharides

Different monosaccharides added in a specific pattern (can be branched/unbranched)

Amylose characterization

1,000-100,000 in MW

Has α1—>4 linkages

Amylopectin

200,000 in MW

Has α1—>4 linkage AND α1—>6 branching

Amylopectin and Amylose in plants (Properties)

Amylose makes up 10% and amylopectin makes up 90%

One reducing end with a bunch of nonreducing ends

Plants chip off nonreducing ends when in need for energy

Glycogen structure

Has α1—>4 linkage AND α1—>6 branching

Why is the glycogen, amylose, amylopectin structure (α1—>4 linkage; α1—>6 branching) so important?

Allows free rotation of the glycosidic bond, resulting in more favorable interactions with side chains and more possible H-bonding interactions.

α1—>4 linkage structure

Helical in nature; good because compact

Cellulose — structure and properties

Structural component in plants; β1—> linked glucose results in a linear polymer with an H-bonding pattern of C₆ and C₅

Chitin — structure and properties

Structural component in insects; β1—> linked glucose results in a linear polymer with an H-bonding pattern of C₆ and C₅

Why are Chitin and Cellulose the way they are (structural)

Free rotation causes H-bonding at certain angles; thus, the bigger structures are locked in.

Monomer structure dictates 3-D structure.

pros and cons of using sugars to carry biological information

Pros: Easy recognition of parts containing weak aq. interactions, massive information density

Cons: Lack of genetic template, rapid breakdown and instability

Composition of Nucleotides

Pentose (β-Ribose)

Purine/pyrimidine base (attached to Pentose 1’ carbon)

Phosphate(s) attached to 4’ carbon through phosphodiester bonds

Pyrimidine (binding)

Binds to pentose on N₁

Purine (binding)

Binds to pentose at N₉

Adenine (weak aqueous interactions)

N₁ is H-bond acceptor

NH₂ group is H-bond donor

Guanine (weak aqueous interactions)

C=O is H-bond acceptor

N₁ and NH₂ are donors

DNA/RNA structural similarities and differences

Similarities: 1’ carbon’s —OH is where bases attach by glycosidic bonds.

Differences: RNA has a 2’ —OH and DNA has a 2’ —H.

Phosphodiester linkage

Links the 5’ CH₂ to the phosphate group(s), giving it a good electrophile.

3’ Carbon on pentose (β-Ribose)

Acts as the nucleophile for DNA/RNA polymer synthesis.

Nucleophilic Substitution Reaction steps

1) 3’ —OH attacks 5’ triphosphate

2) Electrons get kicked into the =O, forming an oxyanion (intermediate)

3) Bond is broken between P and O to resolve the intermediate

4) Electrons get sent to the oxygen, resulting in a phosphate leaving group

Nucleophilic Substitution Thermodynamics

Can only use a triphosphate because you need a good leaving group

Phosphoanhydride bond breaking is FAVORABLE

Results in a PPi, which also contains a phosphoanhydride bond that can be hydrolyzed into 2 Pi.

DNA Structure formation

Contain 2 antiparallel 5’ and 3’ ending strands

Bases are located in center

Major and minor groove (not symmetrical)

5’ end of DNA

Contains phosphodiester

3’ end of DNA

Contains hydroxyl

A,T,G,C hydrogen bonding

A and T form 2 H-bonds

C and G form 3 H-bonds

DNA in terms of Chargaff’s rules

For every A, we need a T and for every G we need a C.

Every purine needs a pyrimidine

Results in consistent width of helix between the phosphodiester backbone

Double helix stability (weak aqueous forces)

PO₄ are oriented away from each other

DNA has divalent metal iosn that help balance the negative charge on the phosphate (Mg²⁺)

Van der Waal interactions allow each base pair to stack on top of the next pair.

Trends in Stacking energy

As we go down on G-C content and get more A-T’s, stabilization decreases due to A-T base pairs not stacking as well as G-C

(good VDW interactions arent formed between A-T base pairs)

Why doesn’t DNA have a 2’ hydroxy like RNA?

Prevents self-cleavage of 2’ —OH and phosphodiester backbone (Nu: right next to Phosphodiester backbone)

Long-term durability is provided due to increased stability of phosphodiester backbone’s hydrolysis resistance.

Why DNA uses Thymine instead of Uracil

Cytosine spontaneously loses an amine group over time and that transfers to uracil, which would cause permanent and irreversible mutations during DNA replication.

Effect of Structure on physical properties of Fatty Acids

Saturated FAs can organize well

When mixing saturated and unsaturated FAs, all of the kinked backbones disrupt VDW interactions and hydrophobic effect. Results in less stabilization

Melting point trends for Saturated FAs (single bond)

As number of carbons increases, melting point increases

(due to the molecules wanting to stay together. More energy required to break them; more favorable interactions)

Melting point trends for Saturated FAs (double bond)

As number of double bonds increase, melting point decreases

(due to the kinking of the double bonds reducing surface area and molecules are less tightly packed; less favorable interactions)

Triacylglycerides structure

Built on glycerol molecule (linear 3 carbon structure with —OH attached to each)

—OH’s can attach to FA through ester linkages

Why Glycogen is not good for storing long term energy (Why FA’s are better)

Glycogen is made up of hydroxyl carbons, while triacylglycerides are made up of methylene groups.

Glycogen is already partially oxidized, so they’ve lost reducing power; triacylglycerides are fully reduced.

Glycogen is hydrated and heavier; FAs have no hydration and are smaller.

Glycogen can be quickly released into glucose; FAs are slowly released.

Structural properties of Lipids

Amphipathic (Polar and non-polar sides)

Have 2 FA tails built on a scaffold

Polar head group

Glycerophospholipid Structure

Glycerol backbone

2 FAs linked through ester linkage

Phosphate group

Alcohol

Glycerophospholipid PO₄ purpose

Polar head groups are attached to it

POLAR HEADS MUST ADD POLARITY TO THE MOLECULE

Sphingolipids utilize a different scaffold

Sphingosine brings its own aliphatic carbon chain

FA added through amide linkage

Fat Soluble Vitamins

A, D, E, K

Steroids Structure

4 rings!

Levels of 3D structure for lipids in aqueous environment

Nonpolar tails buried by taking advantage of hydrophobic effects

Micelle

Simplest form of 3D structure

Polar heads pointed out; hydrophobic tails are buried inside “sphere”

Common in detergents

Bilayer

2 layers of FAs: One set facing out towards water and one set facing in towards water (hydrophobic tails sandwiched inside).

Vesicle

Larger sphere with aqueous environment on inside AND outside.

Lipid 3D structure formation (Thermodynamics)

Forms spontaneously (-delta G)

Hydrophobic effect - Order lipids to decrease entropy; MUCH larger increase of entropy of water, results in the increase of water entropy outweighing the entropy decrease

Van der Waals packing: Small attractive force based on surface area of induced dipoles

H-bonding of polar head groups

Common features of biological membranes

Very HARSH:

Nucleus: Contains the genes

Lysosomes: Degrades intracellular debris

Peroxisome: Oxidizes FAs

Mitochondria: oxidizes fuels to produce ATP

Biological membrane common properties

1) Asymmetric - Different inner and outer

2) Impermeable to charged (polar) molecules

3) Membrane is NOT static. They are DYNAMIC due to non-covalent bonding

Membrane impermeability to charged molecules through simple diffusion (thermodynamics)

Charged molecules form favorable interactions with the water molecules around the membrane and when they want to move through, the water molecules can’t come with due to the hydrophobicity of the tails.

Desolvation process has to occur for the polar molecule to pass. Energy starts to increase, causing a desolvation penalty. The energy doesn’t decrease until it crosses completely

Membrane fluidity and temperature

As temperature increases, fluidity increases (If it goes too high, the membrane breaks apart)

As it reaches the critical point, more VDW interactions and packing (hydrophobic effect) to increase stability —> (Saturated FAs increase; Unsaturated FAs decrease)

Individual lipid movement within the membrane

Flip-flop: from one side of the membrane to the other; very slow

Lateral diffusion: moves laterally (same side of membrane); very fast

Individual lipid movement within the membrane (in terms of thermodynamics)

Polar head group moving through the nonpolar tails have to desolvate. Favorable interactions with water are broken and it has to move without the favorable interactions until it gets to the other side.

Lipid rafts

Formed by sphingolipids and cholesterol

Enrich certain regions and can select for certain proteins and molecules to go into those regions

Fluid mosaic definition and ramifications

Smaller pieces that make up a large membrane — Can move around a lot

Gives membranes additional flexibility that can be localized

Importance of membrane curving

Allows molecules to fuse together with non-covalent interactions

Really important for taking things out of the cell, protecting the inside of the cell

Allows them to bring things into the cell through endocytosis

Allows for functional flexibility — properties can be adjusted to fit the other surrounding membranes