- only some proteins have 4° structure which is the association of more than one polypeptide;
- stabilized by the same interactions as 3° structure
Note that these contain less H and more O than hydrocarbons and are thus, less reduced and more oxidized.
1. Functional Groups --carbonyl
group on one carbon
--hydroxyl (--OH) groups on other carbons
2. Classification of Monosaccharides is based upon:
Carbonyl Group Present
- Aldehyde ----> Aldose (-ose is suffix used for sugars)
- Ketone ----> Ketose
or on the No. of C atoms
3 C's ----> Triose 4 C's ----> Tetrose
5 C's ----> Pentose
6 C's ----> Hexose
7 C's ----> Heptose
or both -- e.g. Aldohexose
Let's consider some common sugars which we will encounter later.
3. Trioses: There are only two trioses, and only one of them contains chiral carbons.
4.Pentoses: Ribose is an essential component of nucleotides which are the building block molecules of Nucleic Acids, DNA and RNA. Ribulose plays an important role in the Dark Reactions of Photosynthesis.
5. Hexoses: Hexoaldoses contain 4 chiral carbons ==> 24 = 16 possible isomers; Hexoketoses contain 3 chiral carbons ==> 23 = 8 possible isomers. Only 3 of the most common hexoses are shown.
6. Pentoses and Hexoses (Heptoses also) can form cyclic Structures; this occurs in water when one of the -OH's forms a bond with the carbonyl carbon (also called the anomeric carbon); in water most sugar molecules are in these cyclic structures which can freely interconvert.
7. This way of crawing cyclic structures is somewhat clumsy -- we prefer Haworth Projections:
But Haworth
Projections
still give a misleading
impression of the structure; the rings are not flat but are
puckered.
1. Maltose -- commonly known as malt sugar.
2. Lactose -- commonly known as milk sugar since it's present in high concentrations in milk.
3. Sucrose -- commonly known as table sugar (cane or beet sugar). Glucose and Fructose are joined by a glycosidic bond between their carbonyl carbons.
Hundreds of monosaccharides bonded together. Two Main Functions: Fuel Storage -- starch and glycogen and Structural -- cellulose and chitin (crab shells)
1. Fuel Storage Polysaccharides:
a) Starch: storage of carbohydrates in plants. Contains two types of D-glucose polymer.
a-amylose -- long unbranched chains of D-Glucose joined by a (1-->4) Glycosidic Bonds; these join the -OH of the #4 carbon on one molecule with the anomeric carbon of another.
amylopectin -- long branched chains of D-Glucose. Most molecules are joined by a(1-->4) Glycosidic Bonds like a-amylose; branchpoints are formed by a(1-->6) Glycosidic Bonds which join two chains via the anomeric carbon at the end of one and the #6 carbon in the middle of another. The following diagram shows both types of linkages.b) Glycogen: The main storage polysaccharide of animal cells. Similar to amylopectin with a(1-->4) glycosidic bonds linking D-glucose units; it's highly branched at a(1-->6) glycosidic bonds. Figure 3.14
2. Structural Polysaccharides -- Cellulose -- most abundant structural polysaccharide; found in plants (wood, plant cell walls etc.). Linear unbranched polymer of D-Glucose molecules connected by b(1-->4) Glycosidic Bonds. The chemical bonds linking glucose units in cellulose are very similar to those in starch and glycogen, but cellulose has very different physical properties. It is non-digestible (except by some bacteria) and forms long fibers that are very strong. The b(1-->4) bonds lead to an extended conformation in cellulose with the strands cross-linked by many interchain H-bonds. The a(1-->4) bonds used in starch and glycogen, however, leads to a tightly coiled helical conformation with many -OH groups facing outward where they can H-bond with H2O.
1. Fatty Acids -- long hydrocarbon tail + carboxyl group (carboxylic acid)
a) Palmitic Acid (Palmitate) O
CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CO2- <--carboxyl group--ionized at pH 7
b) Fatty acids nearly always have an even number of C's ----> 16, 18, 20 etc.
c) May contain one or more double bonds--always cis ----> puts a kink in the tail ...Figure 3.20d) FA's have melting points: --long chains ===> high melting points
--short chains ===> low melting points
e) Carboxyl groups are charged at neutral pH CH3(CH2)14COO-
===> molecule is amphipathic, it has both a hydrophobic nature and a hydrophilic nature
2. Glycerol: Three carbon tri-alcohol.
Figure 3.19
3. Fats--solid ===> contain fewer double bonds in FA's; saturated fats
4. Oils--liquid ===> contain many double bonds in FA's ==>polyunsaturated (vegetable shortening is hydrogenated vegetable oil, double bonds are reduced---> solid) Both fats and oils are Tri-Acyl Glycerols and both are very hydrophobic and insoluble in water.
Both Fats and Oils are Tri-Acyl Glycerides or Triglycerides
Phosphatidyl Choline ...Figure 3.21
1. Phospholipids--major types are phosphoglycerides; composed of phosphatidic acid (a diacyl glycerol) + an alcohol bonded via a phospho-ester bond. The phosphate and alcohol groups make a hydrophilic headgroup (polar head) while the fatty acid hydrocarbon chains make two hydrophobic tails of the amphipathic phospholipid.
a) Other common phospholipids contain other alcohols bonded to phosphatidic acid: phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol
b) the properties of a phospholipid are determined by its 2 variable components, 2 fatty acids and 1 alcohol.
2. Steroids: have very different structgures ...Figure 3.24
Phospholipids can form micelles like FA's, but they also form bilayers
1. An amino acid is a carboxylic acid with an amino group on the a-carbon, the C next to -COOH
2. R-Group varies with different aa's. 20 different R-groups differentiate the 20 different common aa's, the aa's found in proteins.
--COOH and --NH2 are weak acid (proton donor) and weak base (proton acceptor) respectively ===> they undergo dissociation and ionization; the structure in H2O at 3 different pH's is shown below:
The form at pH=6 is Electrically neutral even though it still has charged groups ===> there is no net charge; but it is very dipolar as there is a +1 charge on the amino end and a -1 charge on the carboxyl end. This is called a Zwitterion.
These are two possible sterioisomers of an amino acid. ey are mirrrmages ofoe other;these mirrr imges are non-superimposable and are called enantiomers (or enantiomorphs) a type of optical isomer.
Proteins contain only L-isomers of amino acids. D-amino acids are found rarely; bacterial cell walls and some antibiotics contain D-amino acids.
Amino acids are classified according
to their properties which are determined largely by their
R-groups.
See Table
3.2 of Text for structures of
amino acids and classification by properties of their
R-groups.
1. Nonpolar -- these are hydrophobic groups which tend to avoid contact with water; they are often found at the interior of proteins. Glycine (Gly); Alanine (Ala); Valine (Val); Leucine (Leu); Isoleucine (Ile); Methionine (Met); Phenylalanine (Phe); Tryptophan (Trp); Proline (Pro)
2. Polar -- these amino acids contain polar but uncharged functional groups; they are more likely to be found on protein surfaces in contact with water. Serine (Ser); Threonine (Thr); Cysteine (Cys); Tyrosine (Tyr); Asparagine (Asn); Glutamine (Gln).
4. Basic -- these contain basic functional groups and will normally have a positive charge at neutral pH. Lysine (Lys); Arginine (Arg); Histidine (His).
1. The peptide bond is an amide bond; this is formed by condensation of an amine with a carboxyl group by the elimination of a molecule of water. The C-N bond in amides is very different from the C-N bond in amines:
a) it's shorter than the amine C-N bondb) the amide N is not a base; it doesn't accept protons.
2. The amide C-N bond is shorter than in an amine because it has Double Bond Character:
a) The extra pair of bonding electrons are shared (unequally) between the carbonyl O and the amide N so that the amide C-N bond has about 40% double bond character.b) What does this mean structurally?? The 2nd bond in a double bond is a p-bond formed between p atomic orbitals. The bilobed structure of p orbitals prevents rotation about ¹-bonds.
3. The bonds to a-C's are single bonds ===> free rotation about these bonds is permitted restricted only by steric interference of groups (i.e. do things bump into one another?).
Here each planar peptide group is represented by a rectangle connected to a-C's at its vertices.
1.Peptide--a chain (linear) of a few to a dozen or more amino acids linked together by peptide bonds====> dipeptides, tripeptides, tetrapeptides etc.
2. Polypeptide--a large chain (MW several thousand) of amino acids linked together by peptide bonds====> large polypeptide are proteins. Some peptides and polypeptides have biological activity:
a) Hormones--chemical messengers--insulin, glucagon etc.b) Antibiotics--Gramicidin S
c) Enkephalins--natural pain relievers
d) Toxins--from bacteria, animals, plants--aminitin
3. Types of Proteins--large polypeptide; maybe several polypeptides. MW > several thousand.
a) Globular--chain compactly folded, soluble in H2O; examples are enzymes, transport proteins, antibodies, nutrient-storing proteins. May be simple proteins--containing only aa's--or conjugated proteins--polypeptide +prosthetic group (lipoprotein, glycoprotein, metalloprotein, hemeprotein, etc.)b) Fibrous--long molecules, generally H2O insoluble--keratins, silk, collagen elastin.
the sequence of amino acids in a peptide or protein====> the covalent structure.
1. By convention always write sequence of aa's with NH2 end (amino terminus) on the left end and the -COOH end (carboxy terminus) on the right end. The amino terminus is sometimes called the N-terminus and the carboxy terminus the C-terminus.
2. The aa's in a polypeptide are called residues. The sequence of aa's gives proteins special properties. Enormous variety: 100 aa protein (v. small)====> more than 1 x 10130 possible sequences.
3. Sequencing Peptides and Proteins: 1st accomplished in 1953 by Dr. Fred Sanger on insulin (peptide hormone) ===> Nobel Prize
4. Disulfide Bonds: Many protein structures are stabilized by intrachain disulfide bonds formed between 2 molecules of Cysteine to form 1 Cystine; this crosslinks different parts of the polypeptide. ...Figure 3.3
1. Clues to favored types of secondary structure for all proteins came from X-ray diffraction studies of fibrous proteins, Keratins.
a) a-keratin -- hair wool, tortoise shell; characteristic 5.4 Å repeat (0.54 nm) along the fiber axisb) b-keratin -- silk (fibroin) -- characteristic 7 Å repeat.
2. Pauling and Corey -- discovered the planar peptide bond from their study of the structures of small peptides by X-Ray crystallography. They found two types of secondary structure which they named after the types of keratin.
3. a-Helix: This conformation is possible because there are no steric hindrances (nothing gets in the way). But why is it so stable?? H-Bonds are formed between each amide NH and the >C=O 4 aa's further along the helix: >NH......O==C<. The helix is held together by many intrachain H-bonds between amide N-H of each residue and the carboxyl C=O 4 residues further along.
4. b-SHEET--2 or more chains line up in extended conformation. Held together by interchain H-bonds. Exist in both Parallel (all chains run in the same direction) and Antiparallel (neighboring chains run in opposite directions) forms.
1. The way in which a polypeptide chain folds back upon itself to form a compact globular structure is called its Tertiary Structure; a complete description of the tertiary structure includes the positions of all atoms in three-dimensional space. Proteins can be classified based upon the types of secondary structures it contains and the way in which seconary structure is arranged to make the protein's tertiary structure. For example, a protein may contain only a-helix, only b-sheet, or both arranged in various ways. All proteins of a given type have the same tertiaryary structure.
2. Structures of proteins determined by X-ray crystallography show which regions of the globular structure each type of amino acid prefers.
a) charged and polar sidechains (R-groups) on outside (near H2O )b) hydrophobic sidechains on inside (away from H2O ).
3. Each protein molecule:
===> needn't be one continuous polypeptide--e.g.
chymotrypsin and insulin consist of 2-3 chains held together by
disulfide bonds
===> Each type of protein has a unique tertiary structure (determined by sequence of aa's). Proteins which have similar functions often have similar aa sequences which means they have similar secondary and tertiary structures.
4. What stabilizes Tertiary Structure? ...Figure 3.8
a) Hydrophobic Bonds -- It's energetically favorable to have all hydrophobic aa sidechains together in the center with hydrophilic groups on the outsideb) H-Bonds--between sidechains
c) Disulfide Bonds--in some but not all proteins
d) Salt Bonds-Ionic Interactions--between charged R-groups
5. Denaturation Figure 3.9: disruption of secondary and tertiary structure ==> does not require breaking of covalent bonds; can be caused by:
a) Heat (e.g. hard-boiled egg)b) Chemicals----urea, guanidine-HCl, detergents, organic solvents (alcohol, acetone)
Association of more than 1 globular protein to form a multisubunit protein; can form from identical or non-identical subunits. e.g. Hemoglobin (Fig. 3.7) -- 2 a-subunits + b-subunits or Pyruvate Dehydrogenase Complex--48 subunits (polypeptides) of 3 different types. Held together by weak forces:
1. Hydrophobic Bonds Some proteins don't have quaternary structure
2. H-Bonds (MW's 5,000------> 150,000)
3. Salt Bonds Many enzymes have quaternary structure
Evidence for this comes from denaturation/renaturation experiments; many proteins can be completely denatured (disruption of all but primary structure) and will refold in with proper secondary and tertiary structures when returned to their proper environment.
