Biochemistry Flashcards
Covalent bonds
Shared pairs of electrons - strong (200-800kJ/mol), defined length + direction
O-4, N-3, S-2, P-5.
Single bonds allow rotation, different conformations more energetically favourable than others.
Functional groups
Mols w/ carboxyl -CO groups are acids.
Amino groups +ve charged, phosphate groups -ve charge in neutral conditions
Non covalent bonds
Weaker (<30kJ/mol), unequal sharing of electrons between nuclei.
Inc. hydrogen, electrostatic, van der waals, hydrophobic
Differing electronegativity of elements causes polarity: F > O»_space;S = C > H.
S-H has moderate polar bond, C-H non-polar covalent
Hydrogen bonds
Most common dipole-dipole bond, acceptor must be around 1.8nm away + in straight line. 30kJ to break H bonds.
Water mol can form 4 H bonds w/ other mols, 2 as acceptor + 2 as donor.
Donors: amino group, hydroxyl group.
Acceptors: imine, ether, ketone
Electrostatic interactions
Between opposite charges, stringer than H bond + greater distances than other non-covalent bonds.
e.g. acidic + basic a. acids (glutamate + lysine) -> salt bridge or ion pair
Attraction can be weakened by screening of water mol/other ions on protein surface, pairs in hydrophobic interior stronger/more stable
Van der waals
Between permanent or inducible dipoles (C-H), depends strongly on distance.
Inducible dipoles come due to random asymmetry/fluctuations, sum of vdw radius is optimum distance for inducible dipole interaction, force v. small (< 1kJ/mol) - large numbers can stabilise mol e.g. DNA
Hydrophobic interactions
Not bonds, cant engage in H binding as few/no polar bonds in hydrophobic mols.
Increase in entropy, every CH2 group out of water increases entropy (s) by +3kJ/mol so its favourable.
Molecules in water
Water determines shape molecules assume. Is molecular dipole so forms H bonds w/ itself. Can disrupt NaCl lattice by forming hydration shell around ions.
Alanine (carboxyl + amino) very polarised so more soluble, can form H bonds w/ water (solvation), hydrophilic.
Benzene is non-polar + hydrophobic -> reduces entropy as water has reduced motility around it.
Phospholipids amphipathic/amphiphilic, can migrate into micelles/vesicles.
Titration curves
Can study pH of a solution of weak acid by gradually adding small vols of strong base - until molar equivalent reached.
Flattest parts of curve where pH = pKa -> strongest buffering capacity e.g. buffers normally have pK of 6.5-7.5
A. acids (esp glycine) have acidic carboxyl & basic amino so titration curve has 2 pKa values -> amphoteric/amphiprotic.
If pKa > pH then more acid then base, vise versa
Amino acid structure
Zwitterion - under normal conditions have + and - charge.
C is chiral asymmetric. Enantiomers are stereoisomers that are mirror images of each other.
If carboxyl on left then it is L, if on right then it is D enantiomer.
-> mainly L amino acids in proteins
Glycine only a. acid without enantiomeric form (not chiral)
Fischer projection
Positions carboxyl group at top, R group at bottom of central C atom.
If amino group on left it is an L enantiomer, if on right then it is a D enantiomer.
Aliphatic a. acids
Non-aromatic hydrocarbon side chains.
G, A, V, L, I -> V to I have branched side chain
More hydrophobic as you go along.
Proline
Aliphatic a. acid (3C chain) BUT has heterocycle, much less hydrophobic + rotation restricted around N-C
Aromatic a.acids
Ring structures w/ alternating double bonds (delocalised pi electrons), varying hydrophobicity.
F, Y, W, H
-> H can have +ve charge, is a weak acid pKa =6
Both H & W engage in H bonding
Hydroxyl a. acids
Polar groups involved in H bonding as donor + acceptor.
- can from phosphate esters
Y, S, T
Sulphur containing a. acids
C - similar to serine, weak H bonds, much stronger acid, forms disulphide bonds
M - fairly hydrophobic, AUG start codon
Acidic a. acids + their amides
Form salt bridges + polar interactions w/ water (H bonding), negatively charged
D & E
- pKa of side chain ~ 4
Amides are N & Q - not ionisable but highly polar, strong H bond donor/acceptor
Basic amino acids
N atoms w/ free electron pair, +ve charges.
R & K
Arg pK =12.5, Lys pK = 10
Peptide bonds
Formation eliminates ionizable carboxyl + amino groups (removes charge)
Repeating N-C-C unit makes up backbone of peptide chain
Secondary structure
A. acid sequence determines regularly repeating conformations.
a -helices + B strands/sheets
Native conformation is single stable shape of polypeptide chain
Affected by bond rotations + weak non-covalent interactions.
Peptide group always planar/flat, C-N bond has double bond character -> resonance
So no rotation at peptide bond, 6 atoms lie in same plane
Trans + cis conformations of peptide groups
Double bond character means distinct conformations possible about C-N.
Cis is less favourable due to steric interference of a-C side chains
Rotation of N-C(a) bind in proline restricted due to ring structure.
Ramachandran plot can model possible phi (N-C(a))+ psi (C(a)-C) rotations
a-helix
Right handed - backbone turns clockwise from N terminus.
- each C=O (n) from H bind w/ amide hydrogen on residue (n+4)
- all C=O groups point towards C terminus, helix is dipole
- stabilised by many H bonds
Pitch is advance along long helical axis per turn (0.54nm)
Rise is the advance of each residue along long helical axis (0.15nm)
-> 3.6 amino acids per turn
B strands/sheets
Strands - polypeptide chains almost fully extended
Sheets - many strands arranged side by side, stabilised by H bonds between adjacent strands (C=O & -NH), if antiparallel more stability.
-> side chains project alternately above + below B sheet plane -> pleated
Loops - contain hydrophilic residues + found on protein surfaces
Turns - loops w/ 5 residues or less
^^ have both B-strands + a-helices
Tertiary structure
Stabilised mainly by non-covalent interactions + disulphide bridge formation.
Hydrophobic residues on isde (entropically favourable)
Determined by X-ray + NMR, sorted patterns into motifs/supersecondary structure + domains
Motifs
At least 2 connected secondary structure elements
- helix-turn-helix, helix-loop-helix
- Coiled coil, long loose coils of 2 proteins w/ hydrophobic interactions
- BaB unit, B strands parallel joined via a-helix
- helix bundle, 3-5 helices
- beta hairpin
- Greek key, mainly B strands
Domains
Independently folded, compact units in proteins, cant be connect via loops
e.g. pyruvate kinase has 3 distinct domains
(often standalone function)
-> illustrate evolutionary conservation of proteins (cyt C highly conserved single domain protein)
Carbohydrate structures
Empirical formula (CH2O)n
Oligosaccharides: 2-20 mon.
Polysaccharides: >20 mon.
Glycoconjugates: linked to proteins/lipids.
2 monosaccharide families: aldoses (=O oxidation at C1), ketoses (=O oxidation at C2)
Glyceraldehyde is smallest triose, asymmetric C2 atom so chiral (enantiomers)
Fischer projection in carbs
Most oxidised C at top (=O), if OH on left (L), if OH on right (D).
-> D isomers more common nature
D/L determined by C furthest away from aldehyde/ketone.
Diastereomers are optical isomers that are not enantiomers.
Hayworth projection
More realistic view of carbohydrate - ring formation.
Pentoses + hexoses are cyclic
Hemiacetal isomeric forms (anomers)
At C1 atom:
- B has OH at C1 on top
- a has OH at C1 on bottom
Sugars w. 6 membered ring (5C+O) - pyranoses (hexoses)
Sugars w/ 5 membered ring (4C+O) - furanoses (pentoses)
Glycosidic bond
Links monosaccharides: anomeric C1 binds OH group (hemiacetal -> acetal)
a1->4 forms bent chain
B1->4 forms straighter chain
Storage of D-glucose
Starch: mixture of amylose + amylopectin
- Amylose is D-gluc in compact helical spiral (a1->4 bonds)
- Amylopectin is D-gluc in branched chain (linked by a1->6 binds), branches every 24-30 glucose units
Glycogen: similar structure to amylopectin but larger + more branches (every 8-12 residues)
-> more compact + faster metabolism
Structural functions of D-glucose
Cellulose: plant cell wall, B1->4 linkages so straight unbranched chains, H bonds w/ adjacent chain to form fibrils -> insoluble polymer
Can also be linked to proteins for recognition, adhesion, secretion.
- O-glycosylation in Ser + Thr residues (-Oh group) forms (a) linkage
- N-glycosylation in Asn residue (-CONH2 group) forms (B) linkage
e.g. elastase is secreted serum glycoprotein w/ linked carbs on surface
Nucleic acids
Monomers has 5C sugar, heterocyclic N base + P group
- sugar can be ribose or deoxyribose (C2 has no OH group)
Deoxynucleotide triphosphates (dNTPs) linked by phosphodiester binds between 3C & 5C
-> pyrophosphate lost from dNTP
- purines (A/G) larger
- pyrimidines (T/C)
2 H bonds between A & T, 3 between G & C
Triacylglycerols
Glycerol backbone w/ 3 fatty acid (acyl) groups attached - hydrophobic.
- important fuel source
- 3 f. acids esterified to glycerol
Glycerophospholipids
Glycerol backbone w/ phosphate moieties, polar head group (can have glycol-conjugates) - amphipathic.
- most abundant lipid in membranes
- 2 f. acids esterified to glycerol
- 1 P esterified to C3 on glycerol, small polar head group pinked to it
Sphingolipids
Built on sphingosine backbone, often has glycol-conjugates - amphipathic.
Ceramide (f. acid chain) added to sphingosine to make it amphipathic.
- sphingomyelin has N & P
- cerebroside has glucose or galactose
- ganglioside has complex oligosaccharide
Isoprenoids
Formed from isoprene (5C block), inc steroids, lipid vitamins, hormones e.g. cholesterol
- largely hydrophobic w/ variable polar group content
e.g. cholesterol is amphipathic w/ small polar head group, component in membranes, precursor to other steroids
-> has fused ring system so less flexible than f. acid chain (fluidity buffer for membranes)
Variation in fatty acids
Differ in hydrocarbon length, most 12-22 long, degree of unsaturation + position of double bonds
- can be monounsaturated (oleate) or polyunsaturated (linoleate)
Cis double bonds introduce kinks - fewer vdw interactions so more fluid (lower melting point)
Biological membrane
25-50% lipid, 50-75% proteins
lipids provide permeability barrier, proteins regulate all other processes
2 leaflets of bilayer differ in lipid composition: outer leaflet has mor sphingolipids, more glycerophospholipids in cytosolic leaflet.
Fluid mosaic model - proteins float in lipid bilayer sea
a) lateral diffusion (in leaflet/monolayer) is very rapid
b) transverse diffusion from one leaflet is very slow
3 classes of membrane proteins
Integral - intrinsic/ transmembrane, contain hydrophobic regions + usually span entire bilayer
Peripheral - proteins associate w/ membrane though charge-charge or H bonds to integral proteins or polar head group of mem. lipids, more readily dissociated from mem (pH or ionic strength)
Lipid anchored proteins tethered to mem via covalent bond
- ester/thioester linking Ser/Cys to fatty acyl group
- amide linking N-terminal Gly to fatty acyl group
- Thioether linking Cys to isoprenoid chain
-> all in cytosolic leaflet
- protein can be anchored to GPI by its C terminus (outer leaflet of mem)
Properties of enzymes
Stereospecific - enzymes usually act upon 1 stereoisomer or substrate
Reaction specificity - product yields essentially 100%
Don’t affect equilibrium itself + remain unchanged.
Simply lower activation energy so speed up attainment of reaction equilibrium
