Amino acids are the building blocks of proteins, and can be metabolized to produce energy. Amino acids are especially important at the time of fasting, when the breakdown of muscle protein is a major source of energy and biosynthetic precursors. Some amino acids act as neurotransmitters, and some act as precursors of neurotransmitters, hormones, and a wide variety of other important biochemical compounds

Table of Contents

• Structure of amino acid
• Stereoisomerism
  • d and l (lowercase)
  • D and L (uppercase)
  • D amino acids in biological systems
  • RS system of designating optical isomers

Structure of amino acid

The structure of a single amino acid is shown in Figure below. At the center of this structure is the tetrahedral carbon (C_α), which is linked covalently to both the carboxyl group and the amino group. As we know, that in organic chemistry, the carbon which is directly attached to a carboxyl group is termed as the alpha (α) position, so the amino acids in proteins are all alpha-amino acids. To this α-carbon, hydrogen and a variable side chain is also bonded. The side chain is called R group that gives each amino acid its identity. The side chains (R group) of amino acids provide them their different chemical properties and also allow proteins to have different structures. All the amino acids have both free α-amino and free α-carboxyl groups, except proline.

The amino and carboxyl groups of the amino acids can donate and accept a proton from water. So, it means that, in neutral solution (pH 7), the carboxyl group exists as –COO^– and the amino group as –NH₃⁺. This is so because, carboxylic acids are stronger acids (can donate proton easily, i.e., by increasing the pH slightly) than water, so the carboxyl group of an amino acid (pKa near 2) will donate a proton to water. Similarly, α-amino groups (have pKa greater than 9) are stronger bases (can accept proton readily, and can donate its proton at high pH only) than water and will accept a proton from water. Amino acids in water, therefore, have the general structure (Figure below):

Because the resulting amino acid contains one positive and one negative charge, it is a neutral molecule called a zwitter ion.

Stereoisomerism

All the standard 20 amino acids, except glycine, show optical activity i.e., they can rotate the plane polarized light. Optical activity is exhibited by all compounds that are capable of existing in the forms that are non-superimposable mirror images or enantiomers of each other; such compounds are called chiral compounds. This phenomenon of stereoisomerism is termed chirality. This occurs in all compounds that carry an asymmetric carbon atom i.e., carbon atom that have four different groups. Quantitative measurements of optical activity are usually represented or expressed in terms of the specific rotation, [α]²⁵_D, defined as

For the measurement of optical rotation, the wavelength of the light used and the temperature must both be specified. In this example, D is the “D line” of sodium at 589 nm and 25 refers to a measurement at temperature of 25°C.

d and l (lowercase)

For clear understanding it should be noted that d and l (lowercase) represents dextrorotatory and levorotatory compounds respectively. Some of the α-amino acids isolated from proteins are dextrorotatory (Ala, Ile, Glu etc.) i.e., right handed, while others are levorotatory (Trp, Leu, Phe) i.e., left handed. Dextrorotatory compounds are designated with [+] and levorotatory compounds with [–]. The specific rotation of an amino acid changes with the pH, and also depends on the nature of its R group.

D and L (uppercase)

D and L (upper case) represents the absolute configuration of the four different substituents in the tetrahedron around the asymmetric carbon atom (not optical activity). The compound which is best selected to serve as a standard to explain stereoisomer is three C sugar glyceraldehyde that has an asymmetric carbon atom. Two possible stereoisomers of glyceraldehyde are designated as L and D. The relationship of the amino acid alanine with glyceraldehyde is discussed below

Here, we can easily observe that the amino group on the asymmetric carbon atom of alanine can be stereochemically related to the substituent hydroxyl group on the asymmetric carbon atom of glyceraldehyde, the carboxyl group of alanine can be related to the aldehyde group of glyceraldehyde, and the R group of alanine can be related to the –CH₂OH group of glyceraldehyde. Thus, isomers which are stereochemically related to L-glyceraldehyde are designated as L amino acids, and those which are related to D-glyceraldehyde are designated D amino acids, regardless of the direction of rotation of plane polarized light. Thus, it is important to note that, the symbols D and L refer to absolute configuration, not direction of rotation.

The D and L stereoisomers of any compound have identical physical properties and identical chemical reactivity, with two major exceptions:

• They rotate the plane of polarized light equally but in opposite directions.
• They react at different rates with symmetric and asymmetric reagents.

D amino acids in biological systems

The amino acids, which occur naturally, belong to L stereochemical series. Exceptionally few biological systems have D-amino acids, some examples are antibiotics like tyrosidin, gramicidin and depsipeptide of NAM in peptidoglycan of gram positive bacteria (depsipeptide is the peptide bond formed by the alternate arrangement of D and L amino acids). The amino acids with two asymmetric carbon atoms, threonine and isoleucine, have four stereoisomers, here the other two stereoisomers are called diastereoisomers or alloisomers.

Bacteria require specific enzymes, known as racemases, to inter convert D and L amino acids. Mammals do not use D amino acids, so compounds that block racemases do not affect mammals and show promising antibiotics.

RS system of designating optical isomers

RS system of designating optical isomers was proposed in 1956, by three European chemists; Robert D Cahn, Christopher K Ingold and Vladimir Prelog. This system of nomenclature is also known as CIP system or the R-S system. In this system, each stereo genic center in a molecular is assigned a prefix (R or S). The symbol R is derived from Latin word ‘rectus’ for right, and S from ‘sinister’ for left. The assignment of these prefixes depends on the application of two rules: The sequence rule and the viewing rule.

The rule has following assumptions;

The Sequence Rule

• Assign sequence priorities to the four substituents by looking at the atoms attached directly to the chiral carbon atom.
• The higher the atomic number of the immediate substituent atom, the higher the priority. eg. H<C<N<O<Cl.
• If two substituent’s have the same immediate substituent atom, evaluate the atoms progressively further away from the chiral center until a difference is found. eg. CH₃< C₂H₅< ClCH₂ <BrCH₂< CH₃O.
• If double or triple bonded groups are encountered as substituents, they are treated as an equivalent atom. eg. C₂H₅^– < CH₂ =CH-

The Viewing Rule

Once the priorities of all the four substituents have been determined, the chiral center must be viewed from the side opposite the lowest priority group. If we number the substituent groups from 1 to 4, with, 1 being the highest and 4 the lowest in priority sequence, the two enantiomeric configurations as shown in below along with viewer eye on the side opposite substituent 4.

Here an observer notes whether a curved arrow drawn from the # 1 position to the # 2 location and then to the # 3 position turns in a clockwise or counter-clockwise manner. If the turn is clockwise, the configuration is classified R. If it is counter-clockwise, the configuration is S. Here, it is important to remember that there is no simple or obvious relationship between the R or S designation of a molecular configuration and the experimentally measured specific rotation of the compound it represents.

Related Links

• Amino Acid Classification
• Types of Amino acids
• Non Polar Amino acids
• Polar Amino acids
• MCQs