Cell macromolecules

Condensation reactions

Endergonic reactions which form polymers from their monomeric constituents and generate water as a waste product

300 Da

Avg mr of nucleotide

110Da

Avg mr of amino acid

180 Da

Mr of glucose

Spontaneous reaction

A reaction that can occur without an input of energy, they have a negative change in free energy (deltaG)

Monosaccharide

Monomer of polysaccharides, with general formula (CH₂O)ₙ. Smallest being trioses.

Glyceraldehyde

An aldotriose with 3 carbons and ending in a CH₂OH group. Has a chiral central carbon.

Dihydroxyacetone

A ketotriose ending in a CH₂OH group, non-chiral

Chiral

A molecule which has two forms that are mirror images and non-superimposable.

D (right) or L (left)

Descriptions of the two forms of chiral molecule depending on the direction in which plane polarised light is rotated to. D=right, L=left. Cannot be determined by structure, so structure are compared against d/l glyceraldehyde. Most natural sugars are D-configuration.

D-glyceraldehyde

OH and H group both protrude out of the page, OH on the **right** and H on the left.

L-glyceraldehyde

OH and H both protrude from the page, OH on the left and H on the right.

Example- D-glucose

D-glucose is an extended glyceraldehyde, so is an aldohexose with most similarity to D-glyceraldehyde.

Enantiomers

Chiral mirror images of a molecule.

Stereoisomers

Compounds that have the same molecular formulae but differ in the configuration of atoms in space.

Epimers

Sugars that differ in only a single chiral centre. E.g. D-glucose and D-galactose

Intramolecular cyclisation

Reaction of glucose where the rotation of the bond between C4 and C5, allows the hydroxyl group on C5 to react with the aldehyde on C1 to form a 6-membered ring structure. The PYRANOSE ring.

Pyranose ring

Structure of glucose in which it becomes a 6-membered ring. E.g. α-D-glucopyranose or β-D-galactopyranose

Anomeric carbon

Carbon derived form a carbonyl carbon which becomes a chrial centre

Furanose ring

Structure of fructose in which it becomes a 5-membered ring. E.g. β-D-fructofuranase

α-D-glucopyranose

On C1, OH is **below** H

β-D-glucopyranose

On C1, OH is above H with continuing alternating pattern around the carbon ring.

Chair vs boat form

Tetrahedral bond arrangement around each carbon means the ring is not flat (like benzene) but is puckered, and exists in either a chair or boat form. The chair reform is more stable as there is less oxygen interactions.

Disaccharide

Structure formed when two monosacchrrides are linked together by glycosidic bonds in a condensation reaction between the anomeric carbon on one sugar and a hydroxyl group on the other. (E.g. 1-6, or 1-4)

Cellulose

Polymer formed by polymerisation of β-D-glucose via 1-4 glycosidic linkages. (Disaccharide is cellobiose). Major component of plant cell walls and one of the msot common biopolymers on earth. Adjacent chains hydrogen bond to one another for rigidity.

Glycogen

Polymer formed by polymerisation of α-D-glucose via primarily 1-4, but also 1-6 glycosidic bonds (at branching points) at approx every 10 monomers. Responsible for energy storage in animals.

Starch

Polymer formed by polymerisation of α-D-glucose via 1-4 glycosidic bonds, has far less branching points (either none or one every 30 monomers. Responsible for energy storage in plants.

Reducing sugars

Sugars with a reactive carbonyl group, that can react with oxidising agents. Sucrose is **not** a reducing sugar.

Directionality

Can be assigned to polysaccharide chains based on their reducing and non-reducing end. Branched polysaccharides have multiple non-reducing ends but only one reducing end.

Chitin

β-1,4 polymer of N-acetyl glucosamine. Found in the cell walls of fungi and the exoskeleton of anthropods like insacts.

Glycoprotein

A composite protein/carbohydrate molecule, generally secreted from the cell or inserted into the plasma membrane. Made via addition of an oligosaccharide followed by further carbohydrate chains.

Glycosaminoglycans (GAGs)

Long-chain copolymers of D-glucuronic or L-iduronic acid with N-acetyl-D-glucosamine or N-acetyl-D-galactosamine. High negative charge density repels adjacent cartilage molecules, acting to resist compression under load. E.g. hyaluronic acid

Hyaluronic acid

β-1,4 linked polymer of a β-1,3-linked D-glucoronic acid and N-acetyl-D-glucosamine dimer, up to 50,000 monomers and forms extremely viscous solutions which act as the primary component of synovial fluid in skeletal joints.

Nucleic acid

Major class of macromolecules made of nucleotides. Which are made of a base, pentose sugar and inorganic phosphate.

Purine bases

Adenine and guanine. 2-ringed bases

Pyramidine bases. 1-ringed bases

Cytosine, thymine and uracil

Nucleoside

Same structure as a nucleotide, the base is connected to C1 of the ribose via a β-N-glycosidic bond, but no phosphate is present. Can be ribonucleosides or deoxyribonucleosides.

Nucleotide

Nucleoside with the addition of a phosphoryl group to the 5’ hydroxyl group by a phosphate ester bond. (Can be up to 3 phosphate groups in a row)

3’-5’ phosphodiester linkage

The bond between sugar residues of nucleotides which forms a nucleic acid

Directionality of nucleic acids

5’-end is the end with a free phosphoryl group, 3’-end is the end with a free hydroxyl group. Sequences are written from 5’ to 3’ generally.

Extra methyl group

Difference between thymine (has extra) and uracil

Hydrogen bonding

Occurs when a hydrogen atom that is covalently bound to an electronegative atom (donor) is close enough to another electronegative atom (acceptor). The hydrogen is shared between the two atoms due to small opposing charges. (Strongest when atoms are in a straight line)

Hydrogen acceptors

Carbonyl groups of guanine, thymine and uracil.

Hydrogen donors

Amino groups of adenine and cytosine.

Base pairing

C and G bond to form 3 hydrogen bonds. A and T/U bond to form 2 hydrogen bonds.

DNA double helix

Structure formed when two DNA molecules with opposite directionality (antiparralel) are in close proximity, they spontaneously associate via base pairing to form a right-handed double helix.

10 base pairs

1 complete double helix turn

Cooperative non-covalent interactions

Bonding that occurs between the upper and lower surfaces of each base pair, causing twisting.

Major.minor grooves

Have a major role in sequence-specific DNA recognition

Amino acids

Monomer of protein with identical backbone but differing R groups/side chains

Non-polar sidechains

Alanine, valine, leucine, isoleucine

Charged side chain

Aspartic acid and glutamic acid (negative), arginine and lysine (positive)

Imino acid

Proline

Sulfur-containing side chain

Cysteine and methionine

Aromatic side chain

Phenylalanine, tyrosine and tryptophan

Polar side chain

NH₂- Asparagine and glutamine.

OH- Serine, threonine and tyrosine

Zwitterion

Doubly-charged amino acid ion with negative COO⁻ group and positive NH₃⁺ group, occurs at close to neutral pH. Low pH = positive cation. High pH = negative anion.

pKa of amino acid

The pH of the centre point of the titration

Glycine

The only amino acid (out of 20 total) which does not have a chiral centre as one of its side chains is a hydrogen atom.

L-amino acids

Chirality of naturally-found amino acids.

CORN rule

For L-amino acids, point hydrogen towards you, the groups going clockwise should spell CORN: CO, R and N

Peptide bond

Bond which forms via a condensation reaction, resulting in amine and carboxylate groups losing their charges. Is also rigid and planar with a little plasticity.

Directionality of polypeptide

Has an N-terminus (amino) and C-terminus (carboxyl), numbering and drawing is from N to C

Resonance hybrid

Description of a peptide due to its 40% double bond character.

Stereospecific

Trans peptide bonds are made to ensure sidechains on adjacent residues do not clash,describes protein biosynthesis.

Primary structure

Genetically defined sequence of amino acids.

Secondary structure

Regular structures formed by the backbone of the protein

Tertiary structure

3D organisation of the protein

Quaternary structure

Organisation of subunits in multi-subunit proteins

Edman degradation method

Outdated method of protein sequencing from the N-terminus only suitable for up to \~10 amino acids.

Disulphide bridges

The only other covalent bond in amino acids, forms between cysteine residues. (Rare in intracellular proteins due to the reducing cytoplasmic environment)

Phi (φ)

The angle between the nitrogen and central amino acid carbon.

Psi (ψ)

The angle between the carbon of the carboxylate and the central carbon

Steric hinderance

The process by which psi and phi bond angles are limited by the main chain and the sidechains of adjacent residues.

Ramachandran plot

Plot that shows possible phi and psi angle combinations for L-amino acids.

Exceptions= proline due to pyrrolidine ring of the sidechain (restricts rotation) and glycine which only has H sidechain therefore more steric freedom.

α-helix

Spring like structure, with main chain and side-chain R-groups protruding from the axis of the helix. Stabilised by H bonds between the NH and CO groups (i, i+4 bonding). Often occur at the first level of protein folding due to no 3D folding needed.

5\.4 A

The height of each complete turn of the helix

Helical wheel

Representation of a helix as if looking from the N-terminus, where 2 turns (7 amino acids) are represented by the letters a-g.

β-sheet

Extended polypeptide backbone which forms strands connected by ‘ladders’ of hydrogen bonds. R-groups alternate in protruding above/below the sheet.

Antiparallel

Beta sheet in which the strands run in opposite directions to one another.

Parallel

Beta sheet in which the strands run in the same direction as one another.

Ionic interactions

Interactions between amino acids with a positive (Arg, Lys) and negative (Glu, Asp) charge at physiological pH.

Hydrophobic interactions

Due to the preference for non-polar sidechains to associate with each other rather than the surrounding aqueous environment. (Entropic effect as increases entropy of water)

Van der Waals interactions

Occur when the electron distribution around one atom fluctuates, inducing fluctuations in another nearby atom.

Supersecondary structures

The dissection of tertiary structures into commonly-found combinations of each of the secondary structure types.

β-hairpin

An antiparallel β-sheet where the two strands are connected by a β-turn, involves H bonding.

α-hairpin

When two amphipathic alpha helices form a hydrophobic interface between each other due to hydrophobic and Van der Waals interactions that are reinforced at the edges by H-bonds and ionic interactions.

Four α-helix bundle motif

Motif found in proteins that bind to haem (electron and oxygen carrier). E.g. cytochrome c and myoglobin.

βαβ motif

Found in proteins with parallel β-sheets, proteins that bind to nucleotides usually have this structure in a ROSSMAN FOLD. E.g. lactate dehydrogenase which binds to NADH.

Greek key motif

Basis of the immunoglobulin fold, held together by hydrophobic interactions.

Cryo-electron microscopy

Sample is rapidly frozen to preserve and protect during observation, results in a 3D image

X-ray diffraction

Electrons in the molecule scatter the x-rays, makes a diffraction pattern to make an electron density map.

NMR spectroscopy

Applicable to small proteins in solution, placed into a strong magnetic field and irradiated at radio frequencies to get bond length and a 3D model

Atomic force microscopy

Atomically sharp tip is scanned over a surface to map the topography of the sample.

DNA binding proteins

Diners that can bind to the grooves in DNA. E.g. CRO from bacteriophage lamda is a 2 a-helix dimer that binds to adjacent major grooves on DNA.

Haemoglobin

Contains 4 myoglobin chains as a bundle protein (α-helix), arranged into a tetramer.

Sickle cell anaemia

Mutation on the surface of two haemoglobin monomers that replaces glutamic acid (charged) with valine (hydrophobic). Causes haemoglobin molecules to polymerise due to hydrophobic interactions, causing distortion of the cell in to a sickle shape.

Effects of sickle cell anaemia

Cell rupture, blocking of capillaries and a decreased ability to carry O2.

Ribonuclease

The enzyme that hydrolyses RNA.

Ribonuclease experiement

In the presence of 8M urea and β-mercaptoethanol, the protein is denatured. When they are removed, the protein can spontaneously re fold to the catalytically active form in certain conditions.