CHEMISTRY OF PROTEINS

Zwitter ion German; from zwitter, hybrid  A molecule, especially an amino acid, containing a positively charged ion at one end and a negatively charged ion at the other.

Zwitter ion There is an internal transfer of a hydrogen ion from the -COOH group to the -NH 2 group to leave an ion with both a negative charge and a positive charge. This is called a zwitterion.

A zwitterion is a compound with no overall electrical charge, but which contains separate parts which are positively and negatively charge. This is the form that amino acids exist in even in the solid state. If you dissolve the amino acid in water, a simple solution also contains this ion.

General Amino Acid Structure At pH 7.4 CαCα H R COO-+H 3 N Each of the amino acids used for protein synthesis has the same general structure

Adding an alkali to an amino acid solution If you increase the pH of a solution of an amino acid by adding hydroxide ions, the hydrogen ion is removed from the -NH 3 + group. The amino acid would be found to travel towards the anode (the positive electrode).

Adding an acid to an amino acid solution If you decrease the pH by adding an acid to a solution of an amino acid, the -COO - part of the zwitterion picks up a hydrogen ion. This time, during electrophoresis, the amino acid would move towards the cathode (the negative electrode).

Isoelectric point So when you have added just the right amount of alkali/ acid, the amino acid no longer has a net positive or negative charge. That means that it wouldn't move towards either the cathode or anode during electrophoresis. The pH at which this lack of movement during electrophoresis happens is known as the isoelectric point of the amino acid. This pH varies from amino acid to amino acid.

pI The pI is the “isoelectric point” The pI is the pH where NO charge is on the AA: at pI charge = 0 (Not necessarily at a neutral pH)

General Amino Acid Structure At pH 7.4 CαCα H R COO-+H 3 N Each of the amino acids used for protein synthesis has the same general structure

Isoelectric Point pH at which amino acids exist as the zwitterion (neutral). Depends on structure of the side chain. Acidic amino acids, isoelectric pH ~3. Basic amino acids, isoelectric pH ~9. Neutral amino acids, isoelectric pH is slightly acidic, 5-6.

Zwitterions pH = 1-5 excess H + excess OH - pH = more basic more acidic at pI (isoelectric point) charge = 0 AA’s Ionization states of aminoacids depends on pH

AMINO ACIDS: CLASSIFICATION BASED UPON AMINO ACID SIDE CHAINS Common amino acids can be placed in five basic groups depending on their R substituents: 1. Non-polar and neutral (9) 2. Polar and neutral (6) 3. Acidic and polar (2) 4. Basic and polar (3)

AMINO ACIDS: Polarity of Organic Compounds Principles of Polarity: The greater the electronegativity difference between atoms in a bond, the more polar the bond. Partial negative charges are found on the most electronegative atoms, the others are partially positive. The combination of carbons and hydrogens as in hydrocarbons or in the hydrocarbon portion of a molecule with a functional group is always NON- POLAR.

Polarity Ranking of the Functional Groups: (most polar first) Amide > Acid > Alcohol > Ketone ~ Aldehyde > Amine > Ester > Ether > Alkane

Non Polar Amino Acids have equal number of amino and carboxyl groups and are neutral. These amino acids are hydrophobic and have no charge on the 'R' group. The amino acids in this group are alanine, valine, leucine, isoleucine, phenyl alanine, glycine, tryptophan, methionine and proline. Non-Polar Side Chains

R is alkyl hydrophobic group which can’t enter in hydrogen bond formation. Side chains which have pure hydrocarbon alkyl groups (alkane branches) or aromatic (benzene rings) are non- polar. The number of alkyl groups also influences the polarity. The more alkyl groups present, the more non- polar the amino acid will be. This effect makes valine more non-polar than alanine; leucine is more non-polar than valine. Non-Polar Side Chains

Polar amino acids in which R contains polar hydrophilic group so can forms hydrogen bond with H 2 O. In those amino acids, R may contain: 1- OH group : as in serine, threonine and tyrosine 2- SH group : as in cysteine 3- amide group: as in glutamine and aspargine 4- NH 2 group or nitrogen act as a base (basic amino acids ): as lysine, arginine and histidine 5- COOH group ( acidic amino acids): as aspartic and glutamic

Side chains which have various functional groups such as acids, amides, alcohols, and amines will impart a more polar character to the amino acid. Aspartic acid is more polar than serine because an acid functional group is more polar than an alcohol group Polar Side Chains

Polar Amino Acids with no charge These amino acids do not have any charge on the 'R' group. These amino acids participate in hydrogen bonding of protein structure. The amino acids in this group are serine, threonine, tyrosine, cysteine, glutamine and aspargine.

Acid - Base Properties of Amino Acids Acidic Side Chains If the side chain contains an acid functional group, the whole amino acid produces an acidic solution. Normally, an amino acid produces a nearly neutral solution since the acid group and the basic amine group on the root amino acid neutralize each other in the zwitterion. If the amino acid structure contains two acid groups and one amine group, there is a net acid producing effect. The two acidic amino acids are aspartic and glutamic.

Basic Side Chains If the side chain contains an amine functional group, the amino acid produces a basic solution because the extra amine group is not neutralized by the acid group. Amino acids which have basic side chains include: lysine, arginine, and histidine. Amino acids with an amide on the side chain do not produce basic solutions i.e. asparagine and glutamine. eutralize each other in the zwitterion. If the amino acid structure contains two acid groups and one amine group, there is a net acid producing effect. The two acidic amino acids are aspartic and glutamic.

Polar Amino Acids with Positive Charge Polar amino acids with positive charge have more amino groups as compared to carboxyl groups making it basic. The amino acids, which have positive charge on the 'R' group are placed in this category. They are lysine, arginine and histidine.

Polar Amino Acids with Negative Charge Polar amino acids with negative charge have more carboxyl groups than amino groups making them acidic. The amino acids, which have negative charge on the 'R' group are placed in this category. They are called as dicarboxylic mono-amino acids. They are aspartic acid and glutamic acid.

Polar Amino Acids with Negative Charge

Nonpolar, Aliphatic Amino Acids Glycine is the simplest amino acid, and it really does not fit well into any classification because its side chain is only a hydrogen atom. Aliphatic: In aliphatic compounds, carbon atoms can be joined together in straight chains, branched chains, or non-aromatic rings.

Since their side chains are all nonpolar and therefore hydrophobic, these amino acids are referred to as hydrophobic amino acids. This is true in spite of the fact that the carboxylic acid and amine groups make the individual amino acid molecules polar rather than nonpolar.

Chemical classification Subclassification of neutral amino acids:

Nonpolar Alkyl Groups Glycine, alanine, valine, leucine and isoleucine all contain alkyl side chains. Glycine's side chain consists of a single hydrogen atom. Alanine contains a methyl side chain. Valine contains an isopropyl side chain. Leucine and isoleucine, also have alkyl side chains.

The second group of amino acids consists of the two with hydroxyl groups on their side chains: serine and threonine. Because hydroxyl groups are polar and capable of hydrogen bonding, these amino acids are hydrophilic. Hydroxyl Groups

Sulfur Groups The third group shows the two amino acids with sulfur atoms in their side chains: cysteine and methionine. The amino acid cysteine can, under appropriate conditions, bond to a second molecule of cysteine through its side chain. The resulting bond is between the sulfur atoms of the two cysteine molecules and is called a disulfide bridge. The new molecule that forms is called cystine. This ability of cysteine to form disulfide bridges will turn out to be important in maintaining the structure of some proteins.

Oxytocin Instead of having its amino acids linked in an extended chain, two cysteine residues are joined by an S—S bond. N-terminus C-terminus Ile—Gln—Asn Tyr Cys SS Cys—Pro—Leu—GlyNH

Oxytocin S—S bond An S—S bond between two cysteines is often referred to as a disulfide bridge.

Amide Groups These two amino acids are very similar to the previous, but the side chains contain amide groups instead of carboxylic acid groups. The amide group is customarily written -CONH2 in condensed structural formulas. The amide formed from glutamic acid is called glutamine and the amide formed from aspartic acid is called asparagine.

These two amino acids are easily converted to the original acidic amino acids via hydrolysis reactions that occur in the presence of moderate concentrations of hydronium (or hydroxide ions to make aspartate and glutamate).

Polar Amino Acids with Negative Charge (Carboxylic Acid Groups) Because of the acidity of the carboxylic acid group on the side chain, these amino acids are not only polar, but can become negatively charged because, in solution, the acidic proton is transferred to a water molecule, leaving a negatively charged carboxylate ion.

Monosodium glutamate (MSG) is a salt of glutamic acid that is formed when one of the acidic hydrogen atoms is lost and replaced by a sodium ion.

Amino Groups The sixth group consists of the three amino acids that contain one or more amino groups in the side chain: lysine, arginine and histidine. Because amine groups can accept protons, they are bases and these amino acids are considered basic amino acids. In solution they can accept a proton from water to become positively charged. In arginine and histidine it is the double bonded nitrogen atom that accepts the proton.

Aromatic Groups The next group consists of three amino acids whose side chains contain aromatic ring structures: phenylalanine, tyrosine and tryptophan. Because of its hydroxyl group, tyrosine is polar. Tryptophan, on the other hand, is non-polar in spite of the nitrogen atom in its ring. This is because of the large size of the two combined rings. Phenylalanine is also non-polar.

Looped Group The last amino acid, proline, is unusual in that the side chain bends around to form a ring by bonding to the amine group. Actually this makes the molecule an imino acid rather than an amino acid. It is non-polar and wherever it occurs in a protein, it causes a sharp bend in the chain of amino acids. Flexibility : glycine

Metabolic Fate of Amino Acids