Biological molecules II

Question 1

proteins

Answer 1

Biopolymers of 𝝰-amino acids, largest constituent (apart from water) of cells
Physical/chemical properties are determined by constituent amino acids
The most versatile biomolecules, they have many different functions:
Direct DNA replication, RNA transcription and protein translation
Catalyse the formation and transformation of various biomolecules
Combined with polysaccharides, they signal various processes at cellular interfaces
Regulate the formation of lipid bilayers to modulate membranes’ physical properties
Facilitate the transport of small molecules across membranes to control metabolic activity or signalling cascade reactions

Question 2

amino group is bonded to the 𝝰 ______ atom, next to the carbonyl group

Answer 2

carbon

Question 3

R group is the side chain:

Answer 3

different properties and determine the 3-D structure (folding) and functions of proteins

Question 4

Amino Acids Stereochemistry

Answer 4

α-amino acids are charged at physiological pH (~ 7.4)
Except for glycine, the 𝝰-amino acids are all chiral

Question 5

All the naturally occurring amino acids are found to have the ___ configuration and are classified as ___-amino acids

Answer 5

S
L

Question 6

How many common amino acids?

Answer 6

20 - found in nearly all proteins

Question 7

All L-amino acids can be classified based on

Answer 7

the properties of their R group. In particular, their polarity

Question 8

how to name a.a

Answer 8

Each amino acid has a 3-letter and a 1-letter abbreviation

Question 9

Amino Acids with hydrophobic R groups

Answer 9

In the 3-D structure of proteins, the side chains of these amino acids tend to cluster together internally (hydrophobic effect: stabilises protein 3-D structure).

The inner core of protein 3-D structures contains mainly hydrophobic residues

Question 10

aromatic compounds means….

Answer 10

pi form interactions can be formed (benzene ring)

Question 11

Trp and Tyr are much _____ polar than Phe; Tyr can form H-bonds with its -OH group, which can also be phosphorylated
N on Trp is non basic

Answer 11

more

Question 12

Amino Acids with polar, uncharged R groups

Answer 12

In the 3-D structure of proteins, the side chains of these amino acids can be exposed to the external surface, or buried in the inside: they form hydrogen bonds with water or, if buried, with other polar residues (contributing to secondary and tertiary protein structure)

Question 13

The -OH in Ser and Thr can be ________ (important for regulating the activity of some proteins) or attached to (poly)saccharides (forming glycoproteins)

Answer 13

phosphorylated

Question 14

In 3-D protein structures, these amino acids are rarely buried:

Answer 14

they tend to be exposed to the outer surface and interact with water

Question 15

Arg (guanidinium group) and Lys R group are always _________ charged at physiological pH (~ 7.4)

Answer 15

positively

Question 16

Asp and Glu R groups are always ________ charged at physiological pH (~ 7.4)

Answer 16

negatively

Question 17

His R group has a pKa close to neutral pH:

Answer 17

50% protonated at physiological pH, acts as proton donor or acceptor, depending on environment. Imidazole ring highly coordinating.

Question 18

Name types of a.a

Answer 18

glycin
cystin
alanin

Question 19

Special Amino Acids

Answer 19

Gly: smallest R group: no contribution to hydrophobic effect, found in flexible protein regions

Cys: the –SH group makes it polar. If at an appropriate distance, 2 cysteine residues can react (oxidise) to form a disulphide bond. These bonds are very important to strengthen protein 3-D structures. Although covalent, they are reversible upon reduction

Pro: cyclic secondary amine
(imino acid): rigid conformation, reduces the flexibility of the protein region.
Often found at bends in protein secondary structures.

Question 20

Disulfide bridges cross-linking portions of the polypeptide:

Answer 20

protein folding and 3-D structure

Question 21

What are the essential amino acids that must be provided in diet

Answer 21

Arg, Val, His, Met, Leu, Thr, Lys, Phe, Trp, Iso

Question 22

Acid–Base Properties of Amino Acids

Answer 22

1. High melting points, generally over 200 °C
2. More soluble in water than they are in other common organic solvents
3. Less acidic than most carboxylic acids and less basic than most amines.

In fact, the acidic part of the amino acid molecule is the -NH3+ group, not a -COOH group. The basic part is the -COO- group, and not a free -NH2 group

Question 23

Titration curve for glycine using NaOH

Answer 23

pH 9.6= half of the zwitterionic form has been converted to the basic form

isoelectric pH or isoelectric point (pI):
pH where the amino acid is evenly balanced between the two forms, as the dipolar zwitterion with a net charge of zero

pH 2.3= half of the cationic form has been converted to the zwitterionic form

Question 24

R aspartic acid and glutamic acid:

Answer 24

acidic carboxyl groups. Acidic isoelectric points (pH 2.8 and 3.2). An acidic solution is needed to prevent deprotonation of the lateral carboxylic acid group and to keep the amino acid in its neutral isoelectric state

Question 25

Basic amino acids:

Answer 25

histidine, lysine, and arginine. Basic isoelectric points (pH 7.6, 9.7, and 10.8).
A basic solution is needed in each case to prevent protonation of the basic side chain to keep the amino acid electrically neutral

Question 26

All the other amino acids are considered neutral,

Answer 26

with no strongly acidic or basic side chains. The pI are slightly acidic (from about 5 to 6)

Question 27

Isoelectric point pI:

Answer 27

pH at which concentration of the zwitterion is maximum.
pH at which the concentrations of cationic and anionic forms are equal.

Question 28

Synthesis of Amino Acids

Answer 28

1. Naturally occurring amino acids: hydrolysis proteins and separation of the amino acid mixture
2. Reductive amination: biomimetic (“mimicking the biological process”) synthesis
3. Biological synthesis (biosynthesis) of amino acids

Transamination (biosynthesis, enzyme transaminase)

4. Transamination (biosynthesis, enzyme transaminase)
5. Amination of an 𝝰-Halo Acid
6. The Strecker synthesis
   Step 1: The aldehyde reacts with ammonia to form the imine
   Step 2: Cyanide ion attacks the protonated imine
   Step 3: Hydrolysis

Question 29

Reactions of Amino Acids

Answer 29

1. Esterification of the carboxyl group (in acidic conditions)
2. Acylation of the amino group: formation of amides

Question 30

Polypeptide formation: the peptide bond?

Answer 30

Peptide bond (covalent bond): Amines and acids condense, with the loss of H2O, to form amides

Question 31

Amide linkage formed by ___________ (condensation reaction) between α-carboxylic group of one amino acid and α-amino group of another

Answer 31

dehydration

Question 32

_____________ reaction, thermodynamically unfavourable: carboxylic group must be ACTIVATED to good leaving group. This happens as part of a more complicated process for protein synthesis, called translation, operated by ribosomes.

Answer 32

reversible

Question 33

Peptide sequences are displayed (and read) from _____ to ______, with the free α-amino group (N-terminal) on the left, and the free α-carboxyl group (C-terminal) on the right

Answer 33

left to right

Question 34

Characteristics of peptide bonds:

Answer 34

big role in the 3-D structure of peptides and proteins (“protein folding”)

Question 35

Peptide bonds are rigid and planar

Answer 35

due to resonance, both the C-O and C-N bonds have partial double bond nature (electrons delocalised):

Question 36

Restrict rotation around the C-N bond:

Answer 36

it cannot rotate freely. Rotation is instead permitted around the N-Cα and C-Cα bonds

Question 37

Backbone of polypeptides: defined by a series of rigid plans, with consecutive plans allowed to rotate around the Cα

Answer 37

The rigidity of the peptide bond limits the range of conformations available to polypeptides
ONLY rotations possible

Question 38

Due to conformational restrictions, >99% peptide bonds are in trans configuration
(Cα on either side of peptide bond trans to each other),

Answer 38

with R groups pointing towards opposite sides of the peptide bond. Cis configuration has a greater steric hindrance

Question 39

What is the excemptions of conformation restrictions?

Answer 39

L-proline: ~10% of proline residues in proteins are in cis configuration

Question 40

Breakdown of protein structure

Answer 40

1. the covalent-bonded structure (Amino acid linear sequence)
2. the hydrogen-bonded local 3-D arrangement into an a-helix or a pleated sheet
3. the complete 3-D conformation (Global arrangement of polypeptide chain)
4. the association of two or more peptide units in the active protein (Arrangement of multiple subunits into complexes)

Question 41

Secondary structure

Answer 41

Describes the local spatial rearrangement of the backbone of a protein segment, without considering the position/interactions of R groups

Formation of secondary structures is dictated by the conformational constraints in the peptide sequence, which lead local portions of the peptide to assume specific 3-D arrangements

Formation of these arrangements is mainly directed by hydrogen bonds within backbone atoms between the carbonyl oxygen atoms with the amide (N ¬ H) hydrogens

Question 42

Secondary Structure: alpha-helix

Answer 42

Coil-like structure (phone cord) which involves only one polypeptide chain

Stabilised by H-bonds:
CO of each aa H-bonded to NH of aa that is 4 amino acids further toward the C-terminus (n+4)

Helical wheel: aa composition of a helix. Here 1 and 4 form a salt bridge: stabilises the helix

Backbone atoms on the INSIDE, R groups face the outside
(R groups radial)

Question 43

Polypeptide backbone extended in a zig-zag structure (β-strand: 3-10 aa).
The arrangement of multiple β-strands side by side originates a β-sheet.

Answer 43

R groups of adjacent amino acids protrude from opposite directions of the two rigid planes
The β-sheet is held together by H-bonds (backbone) between adjacent strands

Antiparallel: adjacent β-strands have opposite amino-to-carboxyl orientations. Interstrand H-bonds in-line

Parallel: adjacent β-strands have the same amino-to-carboxyl orientations. Interstrand H-bonds NOT in-line

Question 44

Secondary Structure: loops or turns

Answer 44

Points where a polypeptide chain reverses direction. The most common are β-turns, connecting the ends of two adjacent segments in antiparallel β-sheets.

Points where a polypeptide chain reverses direction. The most common are β-turns, connecting the ends of two adjacent segments in antiparallel β-sheets.

Question 45

Amino acid composition in secondary structures

Answer 45

The formation of secondary protein features is determined by the amino acid composition of a given sequence: certain amino acid compositions tend to form specific secondary structures

α-helices:
alanine, cysteine, leucine, methionine, glutamic acid, glutamine, histidine, lysine
β-sheets:
valine, isoleucine, phenylalanine, tyrosine, tryptophan, threonine
Turns:
glycine, proline, serine, aspartic acid, asparagine

Amino acid sequence (primary structure) directs the local conformations of polypeptide chain (secondary structure), which folds to create an ordered tertiary structure.

Question 46

Tertiary Structure

Answer 46

Overall 3-D arrangement of ALL atoms in a polypeptide (protein) chain, including secondary structure elements, amino acid side chains and additional chemical components (called co-factors).

Protein tertiary structure is given by interactions among regions of secondary structure

Major force stabilising tertiary structure is given by weak interactions (MANY of them!), including H-bonds, ionic and VdW interactions

Predominant weak interactions: hydrophobic effect. Hydrophobic amino acid side chains cluster in the protein’s interior to form a compact hydrophobic core

Tertiary structures can be stabilised by disulfide (covalent) bonds (not common)

Question 47

Quaternary Structure

Answer 47

3-D arrangement of multiple separate polypeptide chains (folded in tertiary structures) into complexes, for proteins that contain >1 polypeptides (subunits).

Complexes of 2 protein molecules are called dimers, of 3 trimers of 4 tetramers (“oligomers”, or “multimers”).
Homo-oligomers formed by identical protein monomers
Heterooligomers formed by different protein monomers

Question 48

Lipids

Answer 48

Molecules that can be extracted from cells and tissues by nonpolar organic solvents

Steroids, prostaglandins, fats, oil, waxes, terpenes, carotenes

Complex lipids:
-easily hydrolysed to simpler constituents
-esters of long-chain carboxylic acids called fatty acids
-two major groups of fatty acid esters are waxes and glycerides
-waxes: esters of long-chain alcohols
-glycerides: esters of glycerol

Simply lipids:
-not easily hydrolysed by aqueous acid or base
-steroids, prostaglandins and terpenes

Question 49

Water-insoluble hydrocarbon derivatives, 3 main functions

Answer 49

Structural components of membranes: phospholipids, cholesterol

High-energy fuel stores: triglycerides stored in adipose tissue
Intracellular signalling

Question 50

Waxes

Answer 50

Esters of long-chain fatty acids with long-chain alcohols

Occur widely in nature and serve a number of purposes in plants and animals

Chemistry of alcohols and esters (acidic or basic hydrolysis)

Question 51

Triglycerides

Answer 51

Glycerides: simply fatty acid esters of the triol glycerol
Triglycerides (triacylglycerols): all three of the glycerol OH have been esterified by fatty acids
Fats: solid at room temperature. Oils: liquid at room temperature
Fats and oils: commonly used for long-term energy storage in plants and animals

Question 52

Triglycerides

Answer 52

Fatty acids of common triglycerides
Derived from two-carbon acetic acid units

Question 53

Saponification of Fats and Oils: Soaps and Detergents

Answer 53

Saponification: base-promoted hydrolysis of the ester linkages in fats and oils

Question 54

Phospholipids

Answer 54

Phospholipids: lipids that contain groups derived from phosphoric acid

Phosphoglycerides: phosphoric acid group in place of one of the fatty acids of a triglyceride

Phosphatidic acids: simplest class of phosphoglycerides. These consist of glycerol esterified by two fatty acids and one phosphoric acid group.