Organic chemistry and Biological chemistry for Health Sciences
59-191
Lecture 18
There is no free rotation about the peptide bond despite having the appearance of a single
bond. The unshared electron pair in the N atom of the NH group interacts with the C and
O atoms of the carbonyl group to give the C-N peptide bond enough of the character of a
double bond to prevent free rotation about it.
Secondary structure:
Several types of secondary structure are particularly stable and occur widely in proteins.
The most prominent are the -helix and  conformations.
-helix:
In the -helix polypeptide chain coils as a right handed screw, which permits all of its
side chains pointing to the outside of the coil. -helix is stabilized by hydrogen bonds
involving H atom of polar NH units to O atoms of carbonyl units situated four residues
further along the backbone.
Generally in long polypeptide only segments of molecules have a -helix configuration.
Uncoiled portion of molecule or a segment with a different feature occurs between helix units.
-PLEATED SHEET:
In this structure adjacent segment of polypeptide chain line up side by side to form a
sheet like array. Often it is slightly pleated and is called -pleated sheet. Side chains
projects above or below the sheets surface. Two to as many as 15 segments of a
polypeptide strand can form a pleated sheet. When the segments of polypeptide strands in
the sheet run in the same direction, they are called parallel -sheet when they are in the
opposite direction they are called antiparallel -sheet.
Tertiary structure:
Tertiary structures are the folding, bending and twisting of the secondary structure. In the
helix the side chains tend to project outward where, in aqueous medium they can be in
contact with water. Even water-soluble protein contains as many as 40% of the
hydrophobic side chains. So the entire helix undergo twisting and folding until the
hydrophobic groups are buried inside, away from water and hydrophilic groups stay
exposed to water.
If cysteines are found in neighboring polypeptide chains the –SH groups in the side chain
can be oxidized to link the two molecules by forming a disulfide bond. Such cross-
linking by disulfide bond can also occur between parts of the same polypeptide molecule
to form a closed loop.
Attraction between positively (NH3+ containing) and negatively (-COO-) charged side
chains also stabilize the tertiary structure of protein. These attractions are similar to the
attraction of ions in a crystal, and are sometimes called a salt bridge.
A non-protein organic compound that associates with a polypeptide, like heme in
myglobin, is called a prosthetic group. It is often the focus of the proteins biological
importance. Heme, for example, is the actual oxygen carrier in myglobin. Heme serves as
oxygen carrier also in hemoglobin.
The heme molecule is held in the folded globin molecule by electrical attraction between
two electrically charged side chains and the Fe2+ ion in heme.
For many proteins native form only emerges only as two or more polypeptides assemble
into a quaternary structure. Individual molecules of polypeptides that make up an intact
protein are called the proteins subunits. Subunits can be identical or different.
Hemoglobin has four subunits, two of one kind ( subunits) and two of another (
subunits). Each subunit has a heme molecule. Combinations of hydrophobic and
electrostatic interactions as well as hydrogen bonds hold the subunits together.
Properties of proteins:
All proteins have some similar chemical properties toward some ordinary substances due
to the presence of similar functional groups.
Hydrolysis of proteins gives a mixture of amino acids. Different digestive enzyme all in
the family of proteases, performs the cleavage of the peptide bonds.
Denaturation is the disorganization of the overall molecular shape of a native protein. It
can occur as an unfolding or uncoiling of helices or as the separation of the subunits.
Denaturation can be caused by many factors. Denaturation is usually accompanied by
loss of solubility.
The protein solubility greatly depends on the pH of the surrounding medium. Because
some side chains as well as the end groups of polypeptide bear electrical charges, an
entire polypeptide molecule can bear a net charge. When all polypeptide molecules have
the same charge (+ve charge due to the presence of NH3+ containing side chains), they
repel each other (and stay in solution). When they have no net charge (isoelectric point),
they clump together to form enormous megaparticles that they drop out of solution.
A protein is least soluble in water when the pH equals the proteins isoelectric point.
Cell membrane proteins:
Concentration gradient of many ions has to be maintained between cells interior and the
fluid outside for the cells to function. Proteins in the membrane maintain the
concentration gradient of those ions.
F.example
Virtually every animal cell maintains a lower concentration of Na+ and a higher
concentration of K+ than is found in its surrounding medium. This imbalance is
established and maintained by an assembly of membrane bound proteins called sodiumpotassium pump. This pump moves Na+ and K+ ions against their concentration
gradient. So this is an example of active transport. This process requires chemical energy
that is provided by ATP.
Some membrane bound proteins also serve as a receptor of hormones and
neurotransmitters. The unique molecular shape of the protein enables its molecules to
recognize the specific substrate, a compound with which it is supposed to interact, among
hundreds of different compounds. So those membrane proteins are the docking place of
the hormones and neurotransmitters in the membrane. Hormone receptor complex
triggers a chain of reactions to result in a cellular response. These way hormones can
regulate the physiological and metabolic processes of the target tissue or organs.
Neurotransmitters also send a signal from one nerve cell to the next by docking to the
membrane protein. Nuerotransmitters released by one cell move to the surface of the next
to bind to the right receptor, which triggers further biochemical changes.
Essentially all cells are sugar coated. Sugars in the cell membrane are mostly
oligosaccharides. Some oligosaccharides are covalently joined to lipids, forming
glycolipids, others are bound to proteins, forming membranes glycoproteins. Most
proteins in the cell membrane are glycoproteins. The oligosaccharides of glycoproteins
generally contain sulfur and nitrogen. Nitrogen is present as an amine or an amide group.
The sugars where NH2 group replaces OH group are called amino sugars. The most
common amino sugar D-glucosamine, occurs as its N-acetyl derivative-N-acetyl-Dglucosamine. These kind of amino sugar are usually joined by N link to a polypeptide at
an aspargine residue.
The N links of oligosaccharides to polypeptides occur most often where the polypeptide
strand is following a bend between segments of secondary structure, like  helices or 
sheets. The oligosaccharide units therefore have little if any direct effect in the tertiary
structure but project, instead from protein surfaces. Oligosaccharide units contribute to
the adhesion between cells and they have critical functions in all of the activities that
depend on the recognition of hormones and neurotransmitters by a cell.