Biological molecules II Flashcards
proteins
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
amino group is bonded to the 𝝰 ______ atom, next to the carbonyl group
carbon
R group is the side chain:
different properties and determine the 3-D structure (folding) and functions of proteins
Amino Acids Stereochemistry
α-amino acids are charged at physiological pH (~ 7.4)
Except for glycine, the 𝝰-amino acids are all chiral
All the naturally occurring amino acids are found to have the ___ configuration and are classified as ___-amino acids
S
L
How many common amino acids?
20 - found in nearly all proteins
All L-amino acids can be classified based on
the properties of their R group. In particular, their polarity
how to name a.a
Each amino acid has a 3-letter and a 1-letter abbreviation
Amino Acids with hydrophobic R groups
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
aromatic compounds means….
pi form interactions can be formed (benzene ring)
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
more
Amino Acids with polar, uncharged R groups
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)
The -OH in Ser and Thr can be ________ (important for regulating the activity of some proteins) or attached to (poly)saccharides (forming glycoproteins)
phosphorylated
In 3-D protein structures, these amino acids are rarely buried:
they tend to be exposed to the outer surface and interact with water
Arg (guanidinium group) and Lys R group are always _________ charged at physiological pH (~ 7.4)
positively
Asp and Glu R groups are always ________ charged at physiological pH (~ 7.4)
negatively
His R group has a pKa close to neutral pH:
50% protonated at physiological pH, acts as proton donor or acceptor, depending on environment. Imidazole ring highly coordinating.
Name types of a.a
glycin
cystin
alanin
Special Amino Acids
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.
Disulfide bridges cross-linking portions of the polypeptide:
protein folding and 3-D structure
What are the essential amino acids that must be provided in diet
Arg, Val, His, Met, Leu, Thr, Lys, Phe, Trp, Iso
Acid–Base Properties of Amino Acids
- High melting points, generally over 200 °C
- More soluble in water than they are in other common organic solvents
- 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
Titration curve for glycine using NaOH
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
R aspartic acid and glutamic acid:
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
Basic amino acids:
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
All the other amino acids are considered neutral,
with no strongly acidic or basic side chains. The pI are slightly acidic (from about 5 to 6)
Isoelectric point pI:
pH at which concentration of the zwitterion is maximum.
pH at which the concentrations of cationic and anionic forms are equal.
Synthesis of Amino Acids
- Naturally occurring amino acids: hydrolysis proteins and separation of the amino acid mixture
- Reductive amination: biomimetic (“mimicking the biological process”) synthesis
- Biological synthesis (biosynthesis) of amino acids
Transamination (biosynthesis, enzyme transaminase)
- Transamination (biosynthesis, enzyme transaminase)
- Amination of an 𝝰-Halo Acid
- 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
Reactions of Amino Acids
- Esterification of the carboxyl group (in acidic conditions)
- Acylation of the amino group: formation of amides
Polypeptide formation: the peptide bond?
Peptide bond (covalent bond): Amines and acids condense, with the loss of H2O, to form amides
Amide linkage formed by ___________ (condensation reaction) between α-carboxylic group of one amino acid and α-amino group of another
dehydration
_____________ 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.
reversible
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
left to right
Characteristics of peptide bonds:
big role in the 3-D structure of peptides and proteins (“protein folding”)
Peptide bonds are rigid and planar
due to resonance, both the C-O and C-N bonds have partial double bond nature (electrons delocalised):
Restrict rotation around the C-N bond:
it cannot rotate freely. Rotation is instead permitted around the N-Cα and C-Cα bonds
Backbone of polypeptides: defined by a series of rigid plans, with consecutive plans allowed to rotate around the Cα
The rigidity of the peptide bond limits the range of conformations available to polypeptides
ONLY rotations possible
Due to conformational restrictions, >99% peptide bonds are in trans configuration
(Cα on either side of peptide bond trans to each other),
with R groups pointing towards opposite sides of the peptide bond. Cis configuration has a greater steric hindrance
What is the excemptions of conformation restrictions?
L-proline: ~10% of proline residues in proteins are in cis configuration
Breakdown of protein structure
- the covalent-bonded structure (Amino acid linear sequence)
- the hydrogen-bonded local 3-D arrangement into an a-helix or a pleated sheet
- the complete 3-D conformation (Global arrangement of polypeptide chain)
- the association of two or more peptide units in the active protein (Arrangement of multiple subunits into complexes)
Secondary structure
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
Secondary Structure: alpha-helix
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)
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.
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
Secondary Structure: loops or turns
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.
Amino acid composition in secondary structures
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.
Tertiary Structure
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)
Quaternary Structure
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
Lipids
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
Water-insoluble hydrocarbon derivatives, 3 main functions
Structural components of membranes: phospholipids, cholesterol
High-energy fuel stores: triglycerides stored in adipose tissue
Intracellular signalling
Waxes
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)
Triglycerides
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
Triglycerides
Fatty acids of common triglycerides
Derived from two-carbon acetic acid units
Saponification of Fats and Oils: Soaps and Detergents
Saponification: base-promoted hydrolysis of the ester linkages in fats and oils
Phospholipids
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.
