Fundamentals of Bioorganic Chemistry (Study Guide) - H. O. Syrova - 2018

Topic

Amino Acid Composition of Proteins and Peptides

Relevance of the topic. Proteins, as the fundamental basis of all living systems, are at the forefront of scientific research. Protein Chemistry has never been a purely "chemical" discipline; rather, it has always integrated the concepts and Methods of biology, medicine, chemistry, and physics. Proteins constitute the material basis of cellular chemical activity. Amino Acids serve as the structural Building Blocks of all proteins. The specific Amino Acid Composition and their sequential arrangement largely determine the properties and physiological Functions of Peptides and Proteins.

General objective: to be able to interpret how the Reactivity of bioorganic compounds depends on The Nature of chemical bonds and the mutual influence of atoms within a molecule; to interpret the reaction mechanisms of various classes of bioorganic compounds and their transformations in biological systems.

Specific objectives:

1. To interpret the Structural Features of Amino acids as the foundation of protein Biopolymers, which act as structural components in all body Tissues.

2. To draw Conclusions regarding the Metabolic pathways of amino acids in the Organism, and to analyze how The formation of physiologically active compounds from them depends on their Structure AND REACTIVITY.

3. To explain The Mechanism of biological amine formation and their impact on the physiological Functions of the organism.

4. To explain the dependence of the PHYSICOCHEMICAL PROPERTIES OF Proteins on their amino acid composition.

5. To analyze Qualitative reactions for a-amino acids in order to determine the Amino acid composition of proteins, and to utilize the biuret test for the Quantitative determination of proteins.

Theoretical questions

1. Composition, structure, and Classification of amino acids.

2. Chemical properties of amino acids.

3. Major Transformations of Amino acids in the organism.

4. Synthesis of amino acids.

1. Amino acids are Organic compounds whose molecules simultaneously contain carboxyl and amino groups. The number of carboxyl groups in a molecule determines its basicity; mono- and dicarboxylic amino acids are of the greatest importance.

Depending on the number of amino groups, mono- and diamino acids are distinguished.

Since amino acids contain different functional groups within their molecules, they are classified as heterofunctional compounds. The general formula for amino acids is:

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where R represents the side chain (side radical).

Based on The structure of their side chain, all amino acids are divided into 4 classes: nonpolar or hydrophobic (Glycine, Alanine, leucine, isoleucine, valine, Proline, phenylalanine, Tryptophan, Methionine); polar, uncharged (Serine, Threonine, Cysteine, Tyrosine, asparagine, glutamine); polar, positively charged (Lysine, Arginine, Histidine); polar, negatively charged (aspartic acid, glutamic acid).

In addition, amino acids are divided into two groups: cyclic and acyclic.

Among acyclic amino acids, the following groups can be distinguished: monoaminomonocarboxylic, monoaminodicarboxylic, diaminomonocarboxylic, and diaminodicarboxylic. Some acyclic amino acids contain sulfur (thioamino acids) or an OH group (hydroxyamino acids). Cyclic amino acids are subdivided into homo- and heterocyclic, depending on whether the ring is formed exclusively by carbon atoms or by

other atoms as well. Homocyclic amino acids include Phenylalanine and Tyrosine; heterocyclic include tryptophan, histidine, and proline.

The isomerism of aliphatic monaminocarboxylic acids is determined by THE POSITION OF the amino group in the molecule relative to the carboxyl group, the STRUCTURE OF THE hydrocarbon radical, and the presence of a chiral carbon atom in the molecule.

The names of aminocarboxylic acids are formed on The basis of trivial or systematic names of the corresponding monocarboxylic acids by adding the prefix "amino-"; the position of the amino group relative to the carboxyl group is designated by numbers or Greek letters.

The simplest aliphatic saturated aminocarboxylic acid is aminoacetic (2-aminoethanoic) acid, commonly known as glycine or glycocoll:

The alanine molecule contains a chiral carbon atom, which is why alanine exists as two mirror-image isomers (enantiomers, optical antipodes):

Aminopropionic acid has two positional isomers regarding the Location OF THE amino group:

D-(-)-alanine rotates the plane of polarization of light to the left, whereas L-(+)-alanine rotates it to the right.

The majority of naturally occurring aminocarboxylic acids belong to the L-series.

All aminocarboxylic acids are crystalline substances, mostly highly soluble in Water.

Aminobutyric acid has three positional isomers depending on the location of the amino group in the molecule:

The molecule of α-aminobutyric acid contains a chiral carbon atom; therefore, it exists in the form of two enantiomers: D-aminobutyric and L-aminobutyric acids.

α-Aminobutyric acid is not involved in the formation of native proteins, but it occurs in biological systems in a free state. The content of this acid in human tissues increases during chronic alcoholism.

γ-Aminobutyric acid (GABA) is a decarboxylation product of glutamic acid:

GABA-based Pharmaceuticals—such as aminalon and gammalon—improve cerebral Blood flow, reduce nervous tension, anxiety, and fear, normalize Sleep, and enhance cognitive performance.

2. Due to the simultaneous presence of carboxyl and amino groups in their molecules, aminocarboxylic acids can react both as acids and as bases.

Some properties of amino acids stem from the mutual influence and interaction of carboxyl and amino groups. The acidic and basic groups within The amino acid molecule react with each other:

Consequently, aqueous solutions of monobasic monoamino acids exhibit a neutral pH environment.

In an acidic medium (pH < 7), zwitterions (dipolar ions) of aminocarboxylic acids are converted into their ammonium cations:

In an alkaline medium (pH > 7), zwitterions are converted into anions.

A characteristic feature of aminocarboxylic acids is their ability to form coordination (chelate) complexes with d-element cations.

For example:

Amino acids with primary amino groups (-NH₂) react with nitrous acid similarly to primary amines (this reaction is used for the quantitative Determination of Amino acids based on the volume of evolved nitrogen via the Van Slyke method):

Another method for the quantitative determination of amino acids is based on their interaction with formaldehyde (Sörensen titration):

Like carboxylic acids, Amino acids can form various derivatives through their carboxyl groups, such as esters, acyl halides, amides, etc.

The varying relative positions of the carboxyl and amino groups in amino acid molecules impart distinct properties to them.

Thus, upon heating, γ-amino acids readily form internal cyclic amides known as lactams:

Some lactams serve as Structural components of pharmaceutical drugs. An example is the nootropic agent (from Greek noos meaning mind) piracetam.

A lactam of γ-aminobutyric acid, such as polyvinylpyrrolidone, is used as a Blood Plasma substitute.

Lactams exhibit lactam-lactim Tautomerism:

Lactams undergo Hydrolysis in the presence of acids or bases, regenerating the corresponding amino acid.

Upon heating, β-aminocarboxylic acids are converted into unsaturated carboxylic acids:

When heated, α-aminocarboxylic acids form cyclic diamides known as diketopiperazines (a consequence of intermolecular dehydration yielding cyclic amides):

In the Presence of water, influenced by an acid or base, diketopiperazines undergo hydrolysis to yield the corresponding amino acids. Under specific non-spontaneous conditions (ΔG > 0) within living organisms, α-amino acids utilize ATP energy to participate in the formation of acyclic amides called peptides:

Tripeptides, tetrapeptides, and so on—collectively known as Polypeptides—can be formed in the very same manner. Back in 1902, Fischer proposed synthesizing peptides from amino acid chlorides:

All peptides undergo hydrolysis when treated with water in the presence of acids or alkalis, yielding α-amino acids.

Among aromatic aminocarboxylic acids, α-aminobenzoic acid and phenylalanine deserve special attention:

p-Aminobenzoic acid stimulates microorganism growth and is classified as a B-complex vitamin. It serves as a Starting Material for synthesizing local anesthetics. Anesthesin and novocaine are particularly widely used:

Novocaine is an ester of p-aminobenzoic acid and diethylaminoethyl alcohol:

This ester is used in the form of its hydrochloride salt, which is highly water-soluble:

3. The Liver acts as the primary chemical Reactor of the living organism, carrying out the most essential transformations of amino acids.

The most important metabolic transformations of amino acids include decarboxylation, deamination (oxidative and reductive), and Transamination:

3,4-Dihydroxyphenylalanine is the product of the hydroxylation of the α-amino acid phenylalanine:

Phenylalanine is one of the 20 amino acids produced during Protein Hydrolysis.

4. From a biological standpoint, amino acids are classified as dispensable (non-essential) and indispensable (essential). Dispensable amino acids are synthesized within the body in sufficient quantities. Since proteins cannot be synthesized in the body from Other Compounds, Essential Amino Acids must be obtained through diet. There are 8 essential amino acids: valine, leucine, isoleucine, threonine, lysine, methionine, phenylalanine, and tryptophan. The remaining 12 amino acids can be synthesized in the body either from Other Amino Acids via transamination or from other compounds.

When not utilized for Protein Synthesis, amino acids within the body are neither accumulated nor excreted. Instead, they are metabolized into intermediates that either undergo complete oxidation to release energy or are converted into glucose, Fatty acids, or Ketone Bodies. This process occurs primarily in the liver. The catabolic pathway for Most amino acids can be divided into two phases:

1) removal of the amino group and its conversion into urea;

2) Conversion of the remaining carbon Skeleton into Pyruvate, acetyl-CoA, or acetoacetyl-CoA.

Amino acids that degrade exclusively to acetyl-CoA or acetoacetyl-CoA are termed ketogenic, because their breakdown is directly linked to the Formation of Ketone bodies. Amino acids whose degradation can lead to the formation of glucose are called glucogenic.

Ketogenic amino acids include leucine and lysine, whereas isoleucine, tryptophan, phenylalanine, and tyrosine can be both Ketogenic and Glucogenic.

Aliphatic amino acids (glycine, alanine) are Proteinogenic Amino Acids that participate in the biochemical processes of the body as structural components of proteins, Enzymes, etc.

Complete the tasks and check your Answers against the answer keys

Task № 1

1. Which carbon atom in aspartic acid is chiral?

А. 1st. B. 2nd. С. 3rd. D. 4th.

2. What is the pH environment of an aqueous solution of lysine?

А. Acidic. B. Basic. С. Neutral. D. Cannot be determined.

3. Decarboxylation is The process of:

A. Destruction of the carboxyl group.

B. Addition to the carboxyl group.

C. Interaction with the amino group.

D. Elimination of water.

Answer keys: 1-B; 2-B; 3-А.

Task № 2

1. Which amino acids are involved in Peptide Synthesis?

А. α-amino acids. B. β-amino acids.

С. γ-amino acids. D. δ-amino acids.

2. Determine the pH of an aqueous solution of cysteine:

А. pH < 7. B. pH > 7. С. pH = 7. D. Can have any value.

3. Transamination in the body results in the formation of:

А. Amines. B. Amides. С. New amino acids. D. Mixtures of various compounds.

Answer keys: 1-А; 2-А; 3-С.

Task № 3

1. The amino acid glycine does not color the indicator in an aqueous solution because it:

А. Does not dissociate. B. Forms an inner salt.

С. Precipitates out. D. Decomposes.

2. In Muscles, unlike the gastrointestinal tract, deamination takes place:

A. Reductive. B. Oxidative.

C. Redox. D. None of the above.

3. The reaction of amino acids with nitrous acid is used for:

A. Carboxyl Group Protection.

B. Amino group protection.

C. Amide synthesis.

D. Quantitative determination of amino acids.

Correct answers: 1-B; 2-B; 3-D.